text:
- Home
- Search for Research Summaries, Reviews, and Reports
EHC Component
- EPC Project
Topic Title
- Treatment Strategies for Women With Coronary Artery Disease
Full Report
- Research Review Aug. 17, 2012
Related Products for this Topic
- Research Protocol Jan. 24, 2011
Executive Summary – Aug. 17, 2012
Treatment Strategies for Women With Coronary Artery Disease
- View PDF (PDF) 591 kB
- Help with Viewers, Players, and Plug-ins
Archived: This report is greater than 3 years old. Findings may be used for research purposes, but should not be considered current.
Table of Contents
- Background
- Objectives of This Review
- Analytic Framework
- Methods
- Results
- Discussion
- Limitations of the Review Process
- Conclusions
- Implications for Future Research
- Glossary
- References
- Full Report
- For More Copies
Cardiovascular disease remains the leading cause of death among women in the United States.1 More than 500,000 women die of cardiovascular disease each year, exceeding the number of deaths in men and the next seven causes of death in women combined. This translates into approximately one death every minute.1,2 Coronary artery disease (CAD)—which includes coronary atherosclerotic disease, myocardial infarction (MI), acute coronary syndrome, and angina—is the most prevalent form of cardiovascular disease and is the largest subset of this mortality. An estimated 16.3 million Americans 20 years of age and older have CAD, and the overall CAD prevalence is 7 percent in adults in the United States (8.3% for men, 6.1% for women). The prevalence of CAD is higher in men than in women across different age groups until they reach 75 years of age, giving the perception that CAD is a male-specific disease.1
This report focuses on women because of the differences in clinical presentation and coronary anatomy, which affect the treatment options for CAD.3-5 Currently available guidelines and systematic reviews provide specific treatment recommendations for women only among a subset of treatment options and overall assume that treatment options are equally effective for both sexes when gender data are not available. However, women have a worse prognosis than men for manifestations of CAD such as acute myocardial infarction, and some data suggest that women and men do not respond equally to the same treatments. Further, women are more likely than men to experience bleeding complications.6-9
In women, CAD is misdiagnosed or not treated as aggressively as in men or is underresearched.10-12 Multiple factors 13 are likely to contribute to the lower use of evidence-based medicine (medical therapy and/or coronary revascularization) and the higher rate of cardiovascular complications among women with CAD.3 These factors include:
- Cardiovascular disease affects women later in life.1,13-15
- At the time CAD is diagnosed, women are more likely to have comorbid factors such as diabetes mellitus, hypertension, hypercholesterolemia, peripheral vascular disease, and heart failure.10
- Women present with angina-equivalent symptoms such as dyspnea or atypical symptoms more often than men.16,17
- The coronary vessels in women tend to be smaller than those of men, which makes them more difficult to revascularize percutaneously and surgically,18 and microvascular disease of the coronary arteries is more common in women than in men.19
- Women tend to have less extensive CAD and a higher proportion of nonobstructive CAD.20,21
- Delay in hospitalization, symptom pattern and recognition, and higher frequency of nonobstructive CAD ultimately results in delay in diagnosis and effective treatment.13,14,22,23
- Because of underrepresentation of women in randomized controlled trials (RCTs), a lack of solid data on cardiovascular disease in women leaves uncertainty about the risk–benefit ratio of treatment.24,25
Thus, a better understanding of the evidence for the effectiveness of medical treatment and revascularization therapies specifically in women is needed in order to reduce cardiovascular events in women.
Clinical Presentations of CAD
Coronary artery disease is the presence of atherosclerosis in the epicardial coronary arteries. Atherosclerotic plaques may either rupture and cause acute ischemia or progressively narrow the coronary artery lumen, resulting in chronic stable angina. Acute myocardial ischemia occurs when an atheromatous plaque ruptures or splits. The reasons for why a specific plaque ruptures when it does are unclear but probably relate to plaque morphology, plaque calcium content, and plaque softening due to an inflammatory process. Rupture exposes collagen and other thrombogenic material, which activates platelets and the coagulation cascade, resulting in an acute thrombus that interrupts coronary blood flow and causes some degree of myocardial ischemia. The consequences of acute ischemia depend on the location and degree of obstruction and range from reversible ischemia (unstable angina) through partial obstruction and tissue damage (non-ST elevation myocardial infarction [NSTEMI]) to complete epicardial occlusions leading to possible transmural infarction of the heart muscle (ST elevation myocardial infarction [STEMI]). The constellation of clinical symptoms that are compatible with acute myocardial ischemia is usually referred to as acute coronary syndrome.26,27
Angina resulting from progressive narrowing of the coronary arteries is the initial manifestation of ischemic heart disease in approximately one-half of patients.28 Angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arm. It is typically aggravated by exertion or emotional stress and relieved by nitroglycerin. Angina usually occurs in patients with CAD that involves at least one large epicardial artery. However, angina can also occur in patients with valvular heart disease, hypertrophic cardiomyopathy, and uncontrolled hypertension. It can also be present in patients with normal coronary arteries and myocardial ischemia related to spasm or endothelial dysfunction. Most angina is a sign of significant CAD—defined angiographically as a stenosis with greater than 70 percent diameter in at least one major epicardial artery segment or with greater than 50 percent diameter in the left main coronary artery. However, some angina is caused by stenotic lesions of lesser diameters, which have much less prognostic significance.28
Unstable angina (UA) is defined as angina with at least one of three features: (1) it occurs at rest or with minimal exertion, (2) it is severe and of recent onset (within the past 4 to 6 weeks), and/or (3) it occurs in a crescendo pattern (i.e., more severe, more prolonged, or more frequent than previously experienced). UA and NSTEMI have a fairly similar pathophysiology, mortality rate, and management strategy when compared with STEMI; therefore they are often grouped together as UA/NSTEMI in clinical guidelines and trial populations. Chronic stable angina is classified as pain that classically occurs with moderate to severe exertion, is milder in nature, and is relieved with rest or sublingual nitroglycerin.
Treatment Options for Patients With CAD
Optimal Medical Therapy
All patients with CAD—regardless of clinical presentation—should receive aggressive management of risk factors for progression of atherosclerosis (smoking, hypertension, hyperlipidemia, and diabetes) combined with pharmacological treatment (antiplatelets, antianginals, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and lipid-lowering drugs).29 Optimal medical therapy of CAD comprises the combinations of these treatments to reduce future cardiovascular events for all the clinical presentations outlined in the previous section. However, patients may not be able to receive optimal medical therapy if they have allergies to, or adverse effects from, individual medications (e.g., aspirin, beta blockers, or cholesterol-lowering drugs) or the combination of medications. Also, the definition of optimal medical therapy continues to evolve as new drugs are developed and as studies are conducted to assess the optimal blood pressure, blood sugar, and lipid goals needed to reduce future cardiovascular events. For medical therapy to be optimized, patients should be prescribed appropriate therapy to reach their therapeutic goal. The effectiveness of medical therapy is also affected by how adherent the patient is to the prescribed therapy.
Coronary Revascularization
Coronary revascularization falls broadly into two categories: coronary artery bypass grafting (CABG) and catheter-based percutaneous coronary intervention (PCI). Together, these coronary revascularization techniques are among the most common major medical procedures performed in North America and Europe. Since the introduction of bypass surgery in 1967 and PCI in 1977, it has become clear that both strategies can contribute to the effective treatment of patients with CAD. CABG and PCI (with or without stents) are alternative approaches in coronary revascularization, so their comparative effectiveness in terms of patient outcomes has been of great interest. The comparative effectiveness of CABG and PCI is an open question primarily for those patients for whom either procedure would be technically feasible or whose CAD is neither too limited nor too extensive.
CABG is generally preferred for patients with very high CAD burden—often described as left main CAD or severe triple-vessel disease with reduced left ventricular function—because CABG has previously been shown in RCTs to improve survival when compared with medical therapy. In contrast, PCI is generally preferred for patients with milder CAD burden—described as single- or double-vessel disease—when symptoms warrant coronary revascularization, in light of its lower procedural risk and evidence that PCI reduces angina and myocardial ischemia in this subset of patients. Uncertainty exists about the choice between PCI and CABG for patients with moderate CAD burden; namely, patients with disease of the proximal left anterior descending artery and less extensive forms of triple-vessel CAD. Most RCTs of PCI and CABG have been conducted in this middle segment of the patient population with CAD. The major advantage of PCI is its relative ease of use and avoidance of general anesthesia, thoracotomy, extracorporeal circulation, central nervous system complications, and prolonged convalescence. Repeat PCI can be performed more easily than repeat bypass surgery, and revascularization can be achieved more quickly in emergency situations. The disadvantages of PCI are early restenosis and the inability to relieve many totally occluded arteries or vessels with extensive atherosclerotic disease. CABG has the advantages of greater durability (graft patency rates exceeding 90% at 10 years with arterial conduits) and more complete revascularization regardless of the morphology of the obstructing atherosclerotic lesion.30
Therefore, patients and clinicians have two or more major treatment approaches to consider for each presentation of CAD. In general, these fall into less invasive (i.e., more medical) approaches and more invasive approaches. Table A summarizes the major treatment options for each clinical scenario described in the sections that follow.
|CAD Presentation
|Treatment Choices
|Abbreviations: CABG = coronary artery bypass grafting; CAD = coronary artery disease; NSTEMI = non-ST elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial infarction
|NSTEMI/unstable angina
|Early invasive management (with PCI or CABG) vs. initial conservative management
|Stable/unstable angina
|PCI vs. CABG vs. optimal medical therapy
Treatment for patients with ST-segment elevation is well established. Patients with STEMI are candidates for reperfusion therapy (either pharmacological or catheter-based) to restore blood flow promptly in the occluded epicardial infarct-related artery. Pharmacological therapy consists of fibrinolysis or conservative/supportive therapy with facilitated antithrombotic medications.27 Multiple randomized trials have demonstrated the benefit of PCI in reducing major cardiovascular adverse events when compared with fibrinolysis or conservative therapy; therefore, immediate revascularization with PCI is the preferred strategy when patients have close access to a catheterization facility. Otherwise, fibrinolysis is recommended (in facilities without access) since it also has been shown to improve cardiovascular outcomes. In older or unstable patients, the use of fibrinolytics can increase bleeding complications; therefore, trials comparing conservative medical therapy to PCI have been performed. In general, patients with STEMI are not treated with CABG (unless emergent from PCI complications) but do receive optimal medical therapy.
Patients with UA/NSTEMI are not candidates for immediate pharmacological reperfusion. The optimal management of UA/NSTEMI has the twin goals of the immediate relief of ischemia and the prevention of serious adverse outcomes (i.e., death or MI). Optimal management is best accomplished with an approach that includes anti-ischemic therapy, antithrombotic therapy, ongoing risk stratification, and in some cases the use of invasive procedures. In addition to aggressive medical therapy, two treatment pathways have emerged for treating patients without ST-segment elevation.26 An initial conservative strategy (also referred to as selective invasive management) calls for proceeding with an invasive evaluation only for those patients whose medical therapy fails (refractory angina or angina at rest or with minimal activity despite vigorous medical therapy) or in whom objective evidence of ischemia (dynamic electrocardiographic changes, high-risk stress test) is identified. An early invasive strategy triages patients to undergo an invasive diagnostic evaluation without first getting a noninvasive stress test or having medical treatment fail. Patients treated with an early invasive strategy generally will undergo coronary angiography within 4 to 24 hours of admission; however, these patients also are treated with the usual UA/NSTEMI medications, including appropriate anti-ischemic, antiplatelet, and anticoagulant therapy. Several RCTs have demonstrated improved clinical outcomes in patients with an invasive strategy, leading to guideline recommendations for invasive approaches to treat patients with NSTEMI and high-risk acute coronary syndrome. Patients with UA/NSTEMI also receive optimal medical therapy.
The treatment of stable angina has two major purposes. The first is to prevent MI and death and thereby increase the quantity of life. The second is to reduce symptoms of angina and occurrence of ischemia, which should improve the quality of life.28 All patients with stable angina are candidates for optimal medical therapy and may be candidates for PCI or CABG based on findings from coronary angiography and if symptoms persist despite optimal medical therapy.
Objectives of This Review
Although CAD is the leading cause of death for women in the United States, treatment studies to date have primarily enrolled men and may not reflect the benefits and risks that women experience. We conducted this systematic review of the medical literature to assess the comparative effectiveness of the major treatment options for CAD specifically in women, evaluating these comparisons:
- PCI versus fibrinolysis or PCI versus conservative/supportive medical management in women with STEMI
- Early invasive versus initial conservative management in women with UA/NSTEMI
- PCI versus CABG versus optimal medical therapy in women with stable or unstable angina
The endpoints assessed were clinical outcomes, modifiers of effectiveness by demographic and clinical factors, and safety outcomes. The following Key Questions (KQs) were considered in this review:
KQ 1. In women presenting with ST elevation myocardial infarction (STEMI):
- What is the effectiveness of percutaneous coronary intervention (PCI) versus fibrinolysis/supportive therapy on clinical outcomes (nonfatal MI, death, stroke, repeat revascularization, recurrent unstable angina, heart failure, repeat hospitalization, length of hospital stay, angina relief, quality of life, or cognitive effects)?
- Is there evidence that the comparative effectiveness of PCI versus fibrinolysis/supportive therapy varies based on characteristics such as:
- Age, race, or other demographic and socioeconomic risk factors?
- Coronary disease risk factors such as diabetes, chronic kidney disease, or other comorbid disease?
- Angiographic-specific factors (number of diseased vessels, vessel territory stenoses, left ventricular function, access site, or prior PCI or coronary artery bypass graft surgery [CABG] revascularization procedure)?
- Hospital characteristics (hospital volume, setting, guideline-based treatment protocols)?
- What are the significant safety concerns associated with each treatment strategy (i.e., adverse drug reactions, radiation exposure, access site complications, renal dysfunction, anaphylaxis, arrhythmias, stent thrombosis, bleeding, infections)?
KQ 2. In women presenting with unstable angina or non-ST elevation myocardial infarction (UA/NSTEMI):
- What is the effectiveness of early invasive (PCI or CABG) versus initial conservative therapy on clinical outcomes (nonfatal MI, death, stroke, repeat revascularization, recurrent unstable angina, heart failure, repeat hospitalization, length of hospital stay, graft failure, angina relief, quality of life, or cognitive effects)?
- Is there evidence that the comparative effectiveness of early invasive versus initial conservative therapy varies based on characteristics such as:
- Age, race, or other demographic and socioeconomic risk factors?
- Coronary disease risk factors such as diabetes, chronic kidney disease, or other comorbid disease?
- Angiographic-specific factors (number of diseased vessels, vessel territory stenoses, left ventricular function, access site, or prior PCI or CABG revascularization procedure)?
- Hospital characteristics (hospital volume, setting, guideline-based treatment protocols)?
- What are the significant safety concerns associated with each treatment strategy (i.e., adverse drug reactions, radiation exposure, access site complications, renal dysfunction, anaphylaxis, arrhythmias, stent thrombosis, bleeding, infections)?
KQ 3. In women presenting with stable or unstable angina:
- What is the effectiveness of the following treatment strategies on clinical outcomes (nonfatal MI, death, stroke, repeat revascularization, recurrent unstable angina, heart failure, repeat hospitalization, length of hospital stay, graft failure, angina relief, quality of life, or cognitive effects)?
- Revascularization (PCI or CABG) versus optimal medical therapy in women with stable angina
- PCI versus CABG in women with stable or unstable angina
- Is there evidence that the comparative effectiveness of revascularization versus optimal medical therapy varies based on characteristics such as:
- Age, race, or other demographic and socioeconomic risk factors?
- Coronary disease risk factors such as diabetes, chronic kidney disease, or other comorbid disease?
- Angiographic-specific factors (number of diseased vessels, vessel territory stenoses, left ventricular function, access site, or prior PCI or CABG revascularization procedure)?
- CABG-specific factors such as type of surgery performed, cardiopulmonary bypass mode (normothermic vs. hypothermic), on-pump versus off-pump, type of cardioplegia used (blood vs. crystalloid), or use of saphenous vein grafts, single or bilateral internal mammary artery grafts, or other types of bypass grafts?
- Hospital characteristics (hospital volume, setting, guideline-based treatment protocols)?
- What are the significant safety concerns associated with each treatment strategy (i.e., adverse drug reactions, radiation exposure, access site complications, renal dysfunction, anaphylaxis, arrhythmias, stent thrombosis, bleeding, infections)?
Analytic Framework
Figure A shows the analytic framework for the systematic review of treatment strategies for women with CAD.
Figure A. Analytic framework
Abbreviations: CABG = coronary artery bypass graft; CAD = coronary artery disease; KQ = Key Question; MACE = major adverse cardiovascular events; MI = myocardial infarction; NSTEMI = non-ST elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial infarction
Input From Stakeholders
During the topic refinement stage, the KQs were refined with the help of an eight-person Key Informant group representing clinicians (cardiology, primary care, cardiac surgery), patients, scientific experts, and Federal agencies. We solicited input from the Task Order Officer and an eight-person Technical Expert Panel (TEP) with experts knowledgeable in CAD, PCI, and CABG throughout our evidence review and followed, based on an a priori research protocol, the Effective Health Care Program's Methods Guide for Effectiveness and Comparative Effectiveness Reviews31 (hereafter referred to as the Methods Guide) for literature search strategies, inclusion/exclusion of studies, abstract screening, data abstraction and management, assessment of methodological quality of individual studies, data synthesis, and grading of evidence for each KQ. All Key Informant and TEP participants were screened for conflicts of interest, and any potential conflicts were balanced or mitigated.
Data Sources and Selection
We included studies published in English from January 1, 2001, through December 12, 2011. Search strategies were specific to each database in order to retrieve the articles most relevant to the KQs. Our search strategy used the National Library of Medicine's medical subject headings (MeSH) keyword nomenclature developed for MEDLINE® and adapted for use in other databases. In consultation with our research librarians, we used PubMed®, Embase®, the Cochrane Database of Systematic Reviews, and the Cochrane Central Registry of Controlled Trials for our literature search. We also searched the grey literature of study registries and conference abstracts for relevant articles from completed RCTs. Grey literature databases included Clinicaltrials.gov; metaRegister of Controlled Trials; ClinicalStudyResults.org; WHO: International Clinical Trials Registry Platform Search Portal; and ProQuest COS Conference Papers Index. The exact search strings used in our strategy are given in Appendix A of the full report. The reference lists of articles applicable to the relevant KQs of two previous Agency for Healthcare Research and Quality (AHRQ) reports related to this topic32,33 and from identified systematic reviews and meta-analyses were manually hand-searched and cross-referenced against our library, and additional manuscripts were retrieved. All citations were imported into an electronic bibliographic database (EndNote® Version X4; Thomson Reuters, Philadelphia, PA).
We developed a list of article inclusion and exclusion criteria for the KQs (Table B). This review focused on randomized controlled studies, since this is the strongest study design for evaluating treatment effectiveness and since observational studies contain potential biases (e.g., patient selection bias, intervention bias) that could affect the clinical outcome. The TEP approved this approach given that the number of abstracts identified in PubMed exceeded 5,000. This review focused on comparisons of treatment strategies; therefore, differences in specific drugs or devices were not investigated and were considered beyond the scope. Using the prespecified inclusion and exclusion criteria, titles and abstracts were examined independently by two reviewers for potential relevance to the KQs. Articles included by any reviewer underwent full-text screening. At the full-text screening stage, two independent reviewers read each article to determine if it met eligibility criteria. At the full-text review stage, paired researchers independently reviewed the articles and indicated a decision to "include" or "exclude" the article for data abstraction. When the paired reviewers arrived at different decisions about whether to include or exclude an article, they reconciled the difference through a third-party arbitrator. Articles meeting our eligibility criteria were included for data abstraction. Relevant review articles, meta-analyses, and methods articles were flagged for manual searching and cross-referencing against the library of citations identified through electronic database searching.
|Study Characteristic
|Inclusion Criteria
|Exclusion Criteria
|Abbreviations: CABG = coronary artery bypass grafting; CAD = coronary artery disease; NSTEMI = non-ST elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST elevation myocardial infarction
|Adult women (≥18 years of age) with CAD and angiographically proven single- or multiple-vessel disease including STEMI, NSTEMI, and stable angina.
|Interventions and comparators
|Article reported original data for any of the interventions compared with another treatment category; or a related methodology paper of an included article:
|Intervention comparisons within the same treatment category such as:
|Outcomes and effect modifiers
|Outcomes and effect modifiers (continued)
|Effect modifiers—individual characteristics including the following:
|Outcomes of women not reported separately from total population.
|Short-term (≤30 days), intermediate-term (1 year), or long-term (>1 year).
|Inpatient or outpatient, primarily primary care and cardiology clinics.
|Study design
|Randomized controlled trial (strongest study design for evaluating treatment effectiveness).
|Publication languages
|English only.
|Given the high volume of English-language publications (including the majority of known important studies), non-English articles were excluded.
Data Extraction and Quality Assessment
The investigative team created forms for abstracting the data elements for the KQs. The abstraction forms were pilot tested with a sample of included articles to ensure that all relevant data elements were captured and that there was consistency and reproducibility between abstractors for accuracy. Based on their clinical and methodological expertise, two researchers were assigned to abstract data from the eligible articles pertaining to the research questions. One researcher abstracted the data, and the second overread the article and the accompanying abstraction form to check for accuracy and completeness. Disagreements were resolved by consensus or by obtaining a third reviewer's opinion if consensus was not reached by the first two researchers. Guidance documents were drafted and given to the researchers as reference material to perform data abstraction, thus aiding in both reproducibility and standardization of data collection.
To aid in both reproducibility and standardization of data collection, researchers received data abstraction instructions directly on each form created specifically for this project with the DistillerSR data synthesis software program (Evidence Partners Inc., Manotick, ON, Canada). We designed the data abstraction forms for this project to collect the data required to evaluate the specified eligibility criteria for inclusion in this review as well as to collect demographics and outcomes. The safety outcomes abstracted included adverse drug reactions, radiation exposure, access-site complications, renal dysfunction, anaphylaxis, arrhythmias, stent thrombosis, bleeding, and infections—the more common adverse events resulting from medical therapy and revascularization. Data on the total population and women and men subgroups were collected. Appendix B of the full report lists the elements used in the data abstraction form. Appendix C contains a bibliography of all studies included in this review, organized alphabetically by author. When appropriate, methods articles providing additional detail were considered when abstracting data for an included study. If a methods article was used as a source for information in the abstraction of a study, it was included in the review and is listed in the bibliography in Appendix C.
Study quality was assessed on the basis of the reported methods and results and performed by two reviewers. We evaluated the quality of individual studies using the approach described in the Methods Guide.31 To evaluate methodological quality, we applied criteria for RCTs that were derived from the core elements described in the Methods Guide. To indicate the summary judgment of the quality of the individual studies, we used the summary ratings of Good, Fair, and Poor based on the study's adherence to well-accepted standard methodologies and adequate reporting.
We used data abstracted on the population studied, the intervention and comparator, the outcomes measured, settings, and timing of assessments to identify specific issues that may have limited the applicability of individual studies or a body of evidence as recommended in the Methods Guide.31 We used these data to evaluate the applicability to clinical practice, paying special attention to study eligibility criteria, demographic features of the enrolled population (e.g., age, race/ethnicity, sex) in comparison with the target population, version or characteristics of the intervention used in comparison with therapies currently in use (e.g., specific components of treatments considered to be "optimal medical therapy," plus advancements in PCI or CABG techniques that have changed over time), and clinical relevance and timing of the outcome measures. We summarized issues of applicability qualitatively. Appendix D of the full report summarizes our assessment of the quality and applicability for each included study.
Data Synthesis and Analysis
We synthesized the primary literature by continuous data (e.g., age, event rates) and categorical data (e.g., race/ethnicity, presence of coronary disease risk factors). We determined the feasibility of completing a quantitative synthesis (i.e., meta-analysis). The feasibility of a meta-analysis depended on the volume of relevant literature (two or more studies), and clinical and methodological homogeneity of the studies. When a meta-analysis was appropriate, we used random-effects models to quantitatively synthesize the available evidence (Review Manager software Version 5.1.; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011). We tested for heterogeneity while recognizing that the ability of statistical methods to detect heterogeneity may be limited. When feasible, we used similar composite outcomes in the meta-analysis for two reasons: (1) a majority of studies reported a composite outcome (e.g., death/MI/stroke/revascularization) as their primary endpoint and (2) many of the studies reported results for women for the primary composite outcome but not for each individual (secondary) outcome. We presented summary odds ratio estimates, standard errors, and confidence intervals for women and men separately to show any similarity or differences.
The majority of outcomes within this report were binary or categorical; therefore, we summarized these outcomes by proportions. We summarized inherently continuous variables, such as age, by mean, median, and standard deviation.
Grading the Body of Evidence
The strength of evidence for each KQ was assessed by using the approach described in the Methods Guide.31 The evidence was evaluated by using the four required domains: risk of bias (low, medium, or high), consistency (consistent, inconsistent, or unknown/not applicable), directness (direct or indirect), and precision (precise or imprecise). Additionally, when appropriate, the studies were evaluated for the presence of confounders that would diminish an observed effect, the strength of association (magnitude of effect), and publication bias. The strength of evidence was assigned an overall grade of high, moderate, low, or insufficient according to the following four-level scale:
- High—High confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect.
- Moderateh—Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of effect and may change the estimate.
- Lowh—Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
- Insufficienth—Evidence either is unavailable or does not permit estimation of effect.
The flow of articles through the literature search and screening process is depicted in Figure B. Of the 13,073 citations identified by our searches, 5,369 were duplicates. Manual searching identified an additional 173 citations for a total of 7,877 citations. After applying inclusion/exclusion criteria at the title/abstract level, 619 full-text articles were retrieved and screened. Of these, 547 articles were excluded at the full-text screening stage, with 72 articles (representing 28 studies) remaining for data abstraction. Appendix E of the full report provides a complete list of articles excluded at the full-text screening stage, with reasons for exclusion.
Abbreviations: CABG = coronary artery bypass graft; CAD = coronary artery disease; KQ = Key Question; NSTEMI = non-ST elevation myocardial infarction; PCI = percutaneous coronary intervention; RCT = randomized controlled trial; STEMI = ST elevation myocardial infarction
Summary of Key Findings
Our search identified 28 comparative studies (72 articles, including methodology and secondary analysis papers). Of the 28 studies, 24 were good quality and 4 were fair quality for their overall reporting of methodology and analysis. A total of 35,597 patients included 10,126 (28%) women. We grouped these by CAD presentation and type of comparison:
- KQ 1: seven studies (six good quality, one fair) comparing PCI with fibrinolysis/supportive (five fibrinolysis, two supportive) in patients with STEMI
- KQ 2: seven studies (six good quality, one fair) comparing early invasive (PCI or CABG) with initial conservative in patients with UA/NSTEMI
- KQ 3: 5 studies (all good quality) comparing revascularization (PCI or CABG) with optimal medical therapy in patients with stable angina (Strategy 1) and 10 studies (8 good quality, 2 fair) comparing PCI with CABG in patients with either stable or unstable angina (Strategy 2). There were a total of 14 studies with 1 study containing data for both comparative strategies.
Table C summarizes the key findings for each KQ, including the modifiers of effectiveness and safety concerns, and provides a grade for the strength of supporting evidence. Detailed reporting of the risk of bias, consistency, directness, precision, and limits to applicability are described in the Summary and Discussion section of the full report.
|Key Question
|Strength of Evidence
|Abbreviations: CABG = coronary artery bypass grafting; CI = confidence interval; MI = myocardial infarction; NSTEMI = non-ST elevation myocardial infarction; OR = odds ratio; PCI = percutaneous coronary intervention; SOE = strength of evidence; STEMI = ST elevation myocardial infarction; t-PA = tissue plasminogen activator; UA = unstable angina
|KQ 1: Women with STEMI (PCI vs. fibrinolysis/ supportive therapy)
|Effectiveness of intervention
1. High (women and men) for short-term (30-day) composite outcomes
2. Insufficient (women and men) for intermediate-term (1-year) composite outcomes
Modifiers of effectiveness
Safety concerns
|7 studies (6 good quality, 1 fair) compared PCI with or without supportive therapy with fibrinolysis or other routine medical care for women with STEMI and contributed evidence about the comparative effectiveness, modifiers of effectiveness, or safety for these interventions. These studies included a total of 4,527 patients, of which 1,174 (26%) were women.
|KQ 2: Women with UA/NSTEMI (early invasive vs. initial conservative)
|Effectiveness of interventions
1. Low (women) and high (men) for short-term (6-month) composite outcomes
2. Low (women and men) for intermediate-term (1-year) composite outcomes
3. Insufficient (women) and low (men) for long-term (5-year) composite outcomes
Modifiers of effectiveness
Safety concerns
|7 studies (6 good quality, 1 fair) compared early invasive (revascularization via PCI or CABG) with initial conservative therapy for women with UA/NSTEMI and contributed evidence about the comparative effectiveness, modifiers of effectiveness, or safety for these interventions. These studies included a total of 17,930 patients, of which 6,084 (34%) were women.
|KQ 3: Strategy 1—women with stable angina (revascularization vs. optimal medical therapy)
|Effectiveness of interventions
1. With the PCI strategy: Moderate (women) and low (men) for long-term (4- to 5-year) composite outcomes
2. With the CABG strategy: Low (women and men) for long-term (4- to 5-year) composite outcomes
3. With both types of revascularization: Moderate (women) and low (men) for long-term (4- to 5-year) composite outcomes
|5 studies (all good quality) compared revascularization (PCI or CABG) with optimal medical therapy for women with stable angina and contributed evidence about the comparative effectiveness, modifiers of effectiveness, or safety for these interventions. These studies included a total of 6,851 patients, of which 1,285 (19%) were women.
|KQ 3: Strategy 2—women with stable/unstable angina (PCI vs. CABG)
|Effectiveness of interventions
1. Low (women and men) for short-term (30-day) composite outcomes
2. Low (women and men) for intermediate-term (1-year) composite outcomes
3. Low (women) and high (men) for long-term (>2-year) composite outcomes
Modifiers of effectiveness
|10 studies (8 good quality, 2 fair) compared PCI with CABG in women with stable/unstable angina and contributed evidence about the comparative effectiveness, modifiers of effectiveness, or safety for these interventions. These studies included a total of 6,289 patients, of which 1,583 (25%) were women.
The findings from this systematic review on the treatment strategies for women across the spectrum of CAD presentations highlight areas for future research and for informing clinical practice. First, this review underscores the significant need for clinical researchers to provide study findings with women-specific data on the primary and secondary clinical outcomes. Overall, we were able to find only 28 relevant studies with data on either shorter term or longer term outcomes in women with CAD treated with invasive or conservative medical therapies. In addition, the representation of women enrolled in these trials was low. Melloni et al.25 found similarly low rates with sex-specific results discussed in only 31 percent of the 156 primary trial publications cited by the American Heart Association's 2007 women's prevention guidelines. In addition, they found that enrollment of women in randomized clinical trials had increased over time (18% in 1970 to 34% in 2006) but remained low relative to their overall representation in disease populations (e.g., 25% women representation in RCTs of CAD compared with 46% women representation in the CAD population).
Second, our findings confirm current practice and evidence for care in one of the three areas evaluated. For women patients with STEMI, we found that an invasive approach with immediate PCI is superior to fibrinolysis in reducing cardiovascular events in women. These findings are similar to a meta-analysis34 of 23 randomized trials comparing PCI with fibrinolysis for acute MI in combined populations of men and women. However, for patients with NSTEMI treated with an early invasive approach compared with a conservative or selective invasive approach, this review did not find statistically significant evidence about the benefit of an early invasive approach in reducing cardiovascular events in women—although our findings did suggest a benefit of early invasive therapy. In contrast, the meta-analysis for trials of early invasive versus conservative strategies in the overall population showed a statistically significant benefit of early invasive therapy.35 The results from this review suggest that such a benefit may also be true in women, but the confidence intervals are too wide to support a firm conclusion.
In addition, for medical therapy alone versus revascularization plus medical therapy for patients with stable angina or high CAD burden, the findings from the current analysis suggest a benefit of revascularization in women. These findings should be viewed with caution because they are based on a limited number of studies with data on 704 (17%) women; these analyses often have both PCI and CABG together in the revascularization group, and the overall findings from these studies do not show a significant benefit beyond angina or symptom reduction for revascularization. In these studies, it is possible that women who present later in life with CAD, and with higher CAD burden, may be obtaining a greater benefit with revascularization, and the findings from this analysis should prompt further research in this area and again encourage researchers to provide data specific on women. In contrast, previous meta-analyses that combined results for men and women found similar outcomes for either treatment. The higher proportion of men enrolled in these trials (83%) may have led to the masking of the women's results by the men's results within a pooled analysis.
Our stakeholder group advised us to assess the effectiveness of these therapies by sex on multiple important clinical outcomes such as nonfatal MI, death, stroke, repeat revascularization, recurrent unstable angina, heart failure, repeat hospitalization, length of hospital stay, angina relief, quality of life, or cognitive effects. A majority of sex-specific reporting was on the composite outcome of major cardiovascular adverse events (death, MI, or revascularization). Individual outcomes by sex were rarely reported, especially on heart failure, repeat hospitalization, length of hospital stay, angina relief, quality of life, or cognitive effects.
Based on the small number of studies that looked at demographic and clinical factors that influence response to treatment strategies in women, there was insufficient evidence that clinicians can use to determine if age, race/ethnicity, socioeconomic status, coronary risk factors, angiographic-specific factors, CABG-specific factors, or hospital-level characteristics should be taken into consideration when deciding a treatment strategy for women with CAD. Unfortunately, more studies are needed that evaluate the subgroups and various demographic and clinical characteristics to fully understand this evidence gap.
In addition, the safety concerns or harms of these treatment strategies are underreported for women enrolled in RCTs. It appears that the bleeding risk may be higher in women receiving fibrinolysis or PCI. Careful consideration should be given to the dose, timing, and duration of antiplatelet, antithrombotic, and anticoagulant therapies administered to women.
Limitations of the Review Process
With 28 studies meeting the inclusion criteria, this systematic review has several limitations. First, our search focused on comparative RCTs—the highest quality of evidence for determining the efficacy of different treatment modalities on cardiovascular outcomes. While this was adequate for evaluating the evidence to support the clinical outcomes by treatment strategy and by CAD presentation for the overall population, there were very few RCTs that reported subgroup analyses by demographic or clinical characteristics and also very few RCTs that reported the harms or risks of therapy. Most studies that reported results applicable to modifiers of effectiveness or safety did this for the overall population and did not separate the effects by sex. We are aware that there are several observational and noncomparator studies of each of the treatment modalities that address these issues in women. Because of the problems with confounding from observational studies and the difficulty of constructing reliable comparisons among single-arm studies, we did not include observational or noncomparator studies in our review.
Second, the sample size and low representation of women in most of the comparator studies may affect the study authors' ability to analyze the results by sex, therefore reducing the number of studies reporting these findings separately (i.e., reporting bias). We excluded 355 articles due to lack of sex-specific reporting of the study results, which resulted in low numbers of studies available for analysis for each clinical presentation (STEMI, UA/NSTEMI, stable angina). Of these 355 articles, 116 were associated with the same 28 studies included in our review, but they did not report data on women separately. The remaining 239 articles were associated with 173 studies that did not report data on women. Figure C presents a graph of the number of articles reporting data on women per year. The percentage ranges from 0 percent (in 1992 and 1993) to 75 percent in 1995. On average, 17 percent of the articles comparing treatment strategies for CAD reported sex-specific outcomes. Of note, many articles included a multivariate analysis that included sex as a covariate in the model; the majority found no evidence of a sex effect. The result of a multivariable model is insufficient for incorporating into a meta-analysis; thus these were excluded from the review. Reporting bias in these publications therefore resulted in selection bias in this review.
Figure C. Number of articles reporting data on women by year
Third, the strength of our meta-analysis is limited by the different definitions of the primary composite outcome and by the timing (short term and long term) of those clinical endpoints. We used our best judgment in choosing which composite outcomes (e.g., death/MI/stroke and death/MI/stroke/revascularization) and time points (e.g., in hospital and 30 days) to combine in the meta-analysis.
A final limitation is the change in PCI techniques and definition of optimal medical therapy over time. Most of the studies involved balloon angioplasty or bare-metal stents. The current era of drug-eluting stents and the use of dual antiplatelet therapy may be underrepresented. Nevertheless, the findings represent the best available evidence. While the treatment options continue to evolve over time, these older therapies (bare-metal stents, balloon angioplasty) are still being used in clinical practice, and therefore we did not downgrade the strength of evidence based on the availability of newer technologies. Medication adherence to beta blockers, angiotensin-converting enzyme inhibitors, aspirin, antiplatelet agents, and lipid-lowering agents were not reported in the studies included in this review. There was also variable reporting on the implementation of optimal medical therapy.
Many of these studies were multicenter, international RCTs with multiple countries represented. The generalizability of those studies to the United States may be of concern; however, the practice of revascularization and prescription of medical therapies are not dramatically different.
From a limited number of studies reporting results for women separately from the total study population, our findings confirm current practice and evidence for care in one of the three areas evaluated.
- For women with STEMI, we found that an invasive approach with immediate PCI is superior to fibrinolysis for reducing cardiovascular events, which is similar to findings in previous meta-analyses combining results for both women and men.
- For women with NSTEMI or unstable angina, we found that, although not statistically significant, the evidence suggests a benefit of an early invasive approach in reducing cardiovascular events, whereas previous meta-analyses of studies comparing early invasive with initial conservative strategies on a combined population of men and women showed a statistically significant benefit of early invasive therapy.
- For women with stable angina, the few trials reporting sex-specific data on revascularization compared with optimal medical therapy showed a greater benefit with revascularization for women, while the men in the study fared equally well with either treatment. In contrast, previous meta-analyses that combined results for men and women found similar outcomes for either treatment.
Implications for Future Research
This comprehensive review of the comparative effectiveness of treatment modalities for women with CAD identified numerous gaps in evidence that would be suitable for future research and for improving the reporting of women findings of cardiovascular therapies in the published literature.
Studies With Sufficient Representation of Women
Sex subgroup analyses are often limited by the number of men or women in each treatment group to allow for adequate power to detect a statistically significant difference in outcome. While we were able to find RCTs that reported risk ratios in women, the enrollment numbers were insufficient to have adequate power to detect a difference, thus resulting in large confidence intervals that often crossed the null effect, with a potential type II error. To better understand the clinical outcomes of women treated by medical therapy or revascularization, trials should be either (1) women-only enrollment or (2) of large enough sample size with stratification of randomization by sex to allow for meaningful sex-based analyses. In order to assess sex differences in treatment modalities and their impact on clinical outcomes, a sufficient sample size is required in order to have adequate statistical power for subgroup analyses.
Patient-Level Meta-Analysis
Given the small representation of women in these RCTs, the heterogeneity of clinical outcomes (e.g., definition of composite outcome) and different measurement time points (e.g., 30 days or 6 weeks for short-term outcomes), we are aware that our group-level meta-analysis may be inadequate (when too few studies are available) to address the comparative effectiveness of medical therapy and revascularization. Therefore, patient-level analysis of trials comparing similar interventions for the same CAD presentation may be more appropriate for assessing the sex differences as well as for conducting subgroup analyses on demographic and clinical factors that influence treatment outcomes, or for evaluating safety concerns/harms of these treatment strategies. Subgroup analyses across trials can be done similarly to a previous AHRQ report on the comparative effectiveness of PCI and CABG, which included an addendum study that pooled individual patient data from 10 randomized trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics (e.g., age, diabetes, sex, individual cardiac risk factors, angioplasty versus bare metal stents).32,36,37
Reporting Sex by Treatment Results Separately
Our review excluded trials that looked for a sex effect yet failed to provide results of women and men by treatment arm. An example is a trial that did a multivariate analysis to assess factors that influenced clinical outcomes and included male (or female) sex in the model, with a finding that it was nonsignificant or significant. We did not contact the corresponding authors of the articles that did not report sex results separately. It would aid future comparisons of treatment modalities if study authors were to report the primary data for women and men separately either within the article itself or in an online supplementary appendix. The 2010 report by the Institute of Medicine on Women's Health Research recommended that funding agencies ensure adequate participation of women and reporting of sex-specific analyses in health research.38
Reporting of Demographic and Clinical Factors That Influence Cardiovascular Outcomes
We found a few studies that conducted subgroup analyses of age, diabetes, and risk stratification in women populations. We did not find any data specific to women on race/ethnicity, socioeconomic factors, chronic kidney disease, angiographic-specific factors, or CABG-specific factors that were listed in KQ 2. Knowing the influence of these factors on cardiovascular outcomes is important for determining the proper treatment strategy and prognosis of women patients who present with various risk factors and comorbidities.
Reporting of Safety Concerns/Risks by Sex
Medical therapy can result in adverse drug reactions, and use of fibrinolytics can result in bleeding or intracranial hemorrhage. PCI can cause access site complications, radiation exposure, contrast-related anaphylaxis, bleeding, and stent thrombosis. CABG can result in wound infections, renal dysfunction, and bleeding. Most studies reported the bleeding risk of revascularization strategies but not the other safety concerns. Systematic reporting of adverse events in publications—in total and by sex—should continue to clarify which treatment modalities are safe for use in clinical practice.
To summarize, these evidence gaps could be addressed in various ways. First, more primary research with adequate representation of women for any of the three CAD clinical presentations could be conducted to achieve adequate statistical power for a sex-based analysis. Second, authors of the comparative trials that were excluded for not reporting sex-based results could be contacted to provide results of women and men by treatment arm, and the group-level meta-analysis could be repeated with a larger number of trials. Alternatively, these authors could be contacted to provide compatible (deidentified) datasets that could be combined for a patient-level analysis to assess the comparative effectiveness, modifiers of effectiveness, and risks of the various treatment strategies available. Finally, the use of observational cohorts from electronic health records could inform the real-world effectiveness of the treatment strategies chosen by clinicians and patients in a nonrandom fashion.
|Agency for Healthcare Research and Quality
|coronary artery bypass graft
|coronary artery disease
|confidence interval
|Key Question
|major adverse cardiovascular events
|myocardial infarction
|non-ST elevation myocardial infarction
|odds ratio
|percutaneous coronary intervention
|randomized controlled trial
|strength of evidence
|ST elevation myocardial infarction
|Technical Expert Panel
|tissue plasminogen activator
|unstable angina
- Roger VL, Go AS, Lloyd-Jones DM, et al. Heart Disease and Stroke Statistics—2012 Update: A Report From the American Heart Association. Circulation. 2012;125(1):e2-e220. PMID: 22179539.
- Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007;115(11):1481-501. PMID: 17309915.
- Shaw LJ, Bugiardini R, Merz CN. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol. 2009;54(17):1561-75. PMID: 19833255.
- Hochman JS, Tamis JE, Thompson TD, et al. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators. N Engl J Med. 1999;341(4):226-32. PMID: 10413734.
- Berger JS, Elliott L, Gallup D, et al. Sex differences in mortality following acute coronary syndromes. JAMA. 2009;302(8):874-82. PMID: 19706861.
- Mieres JH, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation 2005;111(5):682-96. PMID: 15687114.
- Alexander KP, Chen AY, Newby LK, et al. Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) initiative. Circulation. 2006;114(13):1380-7. PMID: 16982940.
- Pepine CJ. Ischemic heart disease in women: facts and wishful thinking. J Am Coll Cardiol 2004;43(10):1727-30. PMID: 15145090.
- Vaccarino V, Abramson JL, Veledar E, et al. Sex differences in hospital mortality after coronary artery bypass surgery: evidence for a higher mortality in younger women. Circulation. 2002;105(10):1176-81. PMID: 11889010.
- Mikhail GW. Coronary heart disease in women. BMJ. 2005;331(7515):467-8. PMID: 16141136.
- Vaccarino V, Parsons L, Every NR, et al. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants. N Engl J Med. 1999;341(4):217-25. PMID: 10413733.
- Daly C, Clemens F, Lopez Sendon JL, et al. Gender differences in the management and clinical outcome of stable angina. Circulation. 2006;113(4):490-8. PMID: 16449728.
- Blomkalns AL, Chen AY, Hochman JS, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol. 2005;45(6):832-7. PMID: 15766815.
- Anand SS, Xie CC, Mehta S, et al. Differences in the management and prognosis of women and men who suffer from acute coronary syndromes. J Am Coll Cardiol. 2005;46(10):1845-51. PMID: 16286169.
- Vaccarino V, Rathore SS, Wenger NK, et al. Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002. N Engl J Med. 2005;353(7):671-82. PMID: 16107620.
- Milner KA, Funk M, Richards S, et al. Gender differences in symptom presentation associated with coronary heart disease. Am J Cardiol. 1999;84(4):396-9. PMID: 10468075.
- Patel H, Rosengren A, Ekman I. Symptoms in acute coronary syndromes: does sex make a difference? Am Heart J. 2004;148(1):27-33. PMID: 15215788.
- Klein J, Karawan A, Abeles-Raviv N, et al. Is there a gender difference in risk profile, attendance, and beneficial effects of a multidisciplinary cardiac rehabilitation program? J Am Coll Cardiol. 2002;39(Supplement 1):1088-1137.
- Kaski J. Cardiac syndrome X. In: Wenger NK and Collins P, eds. Women and heart disease. 2nd ed. London: Informa Healthcare. 2005:205-216.
- Clayton TC, Pocock SJ, Henderson RA, et al. Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial. Eur Heart J. 2004;25(18):1641-50. PMID: 15351164.
- Hochman JS, McCabe CH, Stone PH, et al. Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. TIMI Investigators. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol. 1997;30(1):141-8. PMID: 9207635.
- Kreatsoulas C, Natarajan MK, Khatun R, et al. Identifying women with severe angiographic coronary disease. J Intern Med. 2010;268(1):66-74. PMID: 20210841.
- Wenger NK. Angina in women. Curr Cardiol Rep 2010;12(4):307-14. PMID: 20425162.
- Lee PY, Alexander KP, Hammill BG, et al. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA. 2001;286(6):708-13. PMID: 11495621.
- Melloni C, Berger JS, Wang TY, et al. Representation of women in randomized clinical trials of cardiovascular disease prevention. Circ Cardiovasc Qual Outcomes. 2010;3(2):135-42. PMID: 20160159.
- Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non ST-elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 2007;116(7):e148-304. PMID: 17679616.
- Kushner FG, Hand M, Smith SC, Jr., et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009;120(22):2271-306. PMID: 19923169.
- Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation. 2003;107(1):149-58. PMID: 12515758.
- Sibley C, Rivera J, Blumenthal RS.'ABCDE' makes an effective prevention tool. Cardiology Today: approach translates guidelines into a comprehensive management plan for the primary and seconday prevention of CVD [commentary]. 2007 Jun 1. www.cardiologytoday.com/view.aspx?rid=39071.
- Lansky AJ, Hochman JS, Ward PA, et al. Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professionals from the American Heart Association. Circulation. 2005;111(7):940-53. PMID: 15687113.
- Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and Comparative Effectiveness Reviews, Version 1.0. Rockville, MD: Agency for Healthcare Research and Quality. Draft Posted October 2007. www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=318.
- Bravata DM, McDonald KM, Gienger AL, et al. Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Grafting for Coronary Artery Disease. Comparative Effectiveness Review No. 9. (Prepared by Stanford-UCSF Evidence-based Practice Center under Contract No. 290-02-0017.) Rockville, MD: Agency for Healthcare Research and Quality. October 2007. www.effectivehealthcare.ahrq.gov/ehc/products/15/55/CER_PCI_CABGMainReport.pdf. PMID: 20704052.
- Grady D, Chaput L, Kristof M. Results of systematic review of research on diagnosis and treatment of coronary heart disease in women. Evid Rep Technol Assess (Summ). 2003(80):1-4. PMID: 12827897.
- Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361(9351):13-20. PMID: 12517460.
- Mehta SR, Cannon CP, Fox KA, et al. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA. 2005;293(23):2908-17. PMID: 15956636.
- Hlatky MA, Boothroyd DB, Bravata DM, et al. Addendum to Coronary Artery Bypass Surgery Compared With Percutaneous Coronary Interventions for Multivessel Disease. Comparative Effectiveness Review No. 9 Addendum. (Prepared by Stanford-UCSF Evidence-based Practice Center under Contract No. 290-02-0017.) Rockville, MD: Agency for Healthcare Research and Quality. February 2010. www.effectivehealthcare.ahrq.gov/ehc/products/15/421/CER9%20Addendum%20Final.pdf.
- Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet. 2009;373(9670):1190-7. PMID: 19303634.
- Women's Health Research: Progress, Pitfalls, and Promise. Institute of Medicine of the National Academies, Consensus Report. 2010. www.iom.edu/Reports/2010/Womens-Health-Research-Progress-Pitfalls-and-Promise.aspx .
Full Report
This executive summary is part of the following document: Dolor RJ, Melloni C, Chatterjee R, Allen LaPointe NM, Williams JB Jr, Coeytaux RR, McBroom AJ, Musty MD, Wing L, Samsa GP, Patel MR. Treatment Strategies for Women With Coronary Artery Disease. Comparative Effectiveness Review No. 66. (Prepared by the Duke Evidence-based Practice Center under Contract No. 290-2007-10066-I.) AHRQ Publication No. 12-EHC070-EF. Rockville, MD: Agency for Healthcare Research and Quality. August 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
For More Copies
For more copies of Treatment Strategies for Women With Coronary Artery Disease: Comparative Effectiveness Review Executive Summary No. 66 (AHRQ Pub. No. 12-EHC070-1), please call the AHRQ Publications Clearinghouse at 1–800–358–9295 or email email@example.com.


text:
U.S. Rep. Vern Buchanan is continuing to work to reclassify prescription painkillers, making them harder to prescribe and to obtain.
Buchanan on Monday urged the Food and Drug Administration to adopt the recommendation of its advisory panel, which last week voted 19-10 to place new restrictions on narcotic painkillers containing hydrocodone.
"Prescription drug abuse is wreaking havoc on countless families and communities across our nation," Buchanan and U.S. Rep. Edward Markey, D-MA, wrote a in a letter to FDA Commissioner Margaret Hamburg. "This epidemic has reached such disastrous proportions that fatal drug overdoses now outnumber the total amount of traffic fatalities in this country. Products containing hydrocodone, such as Vicodin and Lortab, are fueling this epidemic."
During the last Congress, Buchanan introduced legislation to reschedule hydrocodone combination drugs from a Schedule III to a Schedule II drug. The legislation, called the Pill Mill Crackdown Act, was endorsed by 58 members of Congress.
To view Buchanan's letter to the FDA, click here.
Contact Pam Eubanks at [email protected].

subset: commoncrawl


text:
You are here:
|Knowledgeability = 10
|Clarity of Response = 10
|Politeness = 10
|No Comment
Answers by Expert:
Depending on the mechanical knowledge off owner, I can answer just about any question they ask. One lady asked about her feed dogs not going back up, some machines will not go back up unless you turn the wheel over, (start sewing). It sounds simple but sometimes you never think of it.
I've been servicing sewing machines since 1989, I still service machines for Northwestern Ontario Canada. It is a large area with little or no service people and I can usually tell on the phone if it can be fixed by the owner.
I took a 2 year apprentice course with a dealer who was looking to teach and hire. I worked for him for 8 years before moving up to the Northwest, Red Lake area of Ontario.
©2017 About.com. All rights reserved.


text:
By Tiernan Ray
Raymond James telecom analyst Simon Leopold today writes in a note to clients that this will be a "challenging" year for telecom equipment suppliers such as Alcatel-Lucent (ALU), Ciena (CIEN), Juniper Networks (JNPR) and others, given a reluctance to spend on the part of operators.
The Q1 results will likely show spending in North America declining 19% from Q4, which Leopold opines is especially bad given "the weakness in 4Q13 when capex grew only 6.3% sequentially, compared to normal sequential growth in the double digits."
Leopold favors those comapnies that sell more to data center builds than to telecom, such as Cisco Systems (CSCO), F5 Networks (FFIV), and Arris (ARRS), all of which he rates Outperform.
We see opposing cross-currents for networking suppliers. On one hand capital spending plans increased for datacenters, yet on the other hand, the trend toward white box (i.e., unbranded) hardware represents a threat that Cisco's CEO acknowledged in interviews. We believe Intel's Romley chips for servers have stimulated networking upgrades such as the Ethernet switch market [...] The trend toward software-centric networks as illustrated by the advent of SDN (software defined networks) and NFV (network functions virtualization) have yet to show up in network equipment vendor results, but this is a long-term trend that likely affects datacenter spending first. Google has already announced deployment of its own SDN, and clearly others are working on such architectures. We believe operators are developing an appreciation for the complexity of evolving to software-centric networks. The transition will be gradual, and we think incumbents that adapt can succeed [...] We consider capital spending from 11 publicly-traded firms where most of the capital budgets go to datacenters. The trends toward cloud computing and virtualization actually drive more networking demand in order to interconnect the storage and server resources, and this is a positive secular trend. Capex from these 11 companies grew 7% sequentially in 4Q13 with most of the upside driven by Facebook and Microsoft. Google disclosed capital expenditures for the quarter of $2.3 billion, more than doubling y/y with growth of 121% from calendar 4Q12. Google management noted that the majority of capex spending was related to datacenter construction, facilities-related purchases and production equipment. We think datacenters benefit from architectural evolutions. Networking equipment vendors typically contribute routing and switching solutions in the range of 5-10% per datacenter project but we believe this is increasing in the mix.
He sees spending being rather light the world-over, despite China's ramp-up of 4G LTE broadband wireless:
Our outlook for 2014 sees total North American carrier spending flat, compared to 2013 growth of 10% and 2012 spending that grew 5% (excluding Sprint, who grew spending 48%, 2013 capex was more modest at ~6%). Additional uncertainty stems from AT&T's Domain 2.0 effort and continued weakness from tier two-and-three carriers. U.S. cable TV is a bright spot with capex growing 10%. Europe offers promise with nominal growth of 12% y/y, but we have yet to observe concrete evidence. Europe is driven primarily by Vodafone's "Project Spring" initiative, which calls for incremental capex of £7.0 billion over the next two years, and excluding Vodafone, we estimate European carrier capex is up modestly. Although we believe our estimates are appropriately conservative and could prove too low, 2014 is still likely to be a low growth year overall. China capex grows 12%, led by the 4G mobile upgrade.
Even good news from China Mobile (CHL) is not going to help, he thinks:
China Mobile provided 2014 capex guidance for 225.2 billion RMB, or a 22% increase. While this is certainly an incremental positive in our view given the previous expectations for a -3% decline, we believe that this has largely been priced in for exposed vendors such as Alcatel-Lucent.


text:
Virtualization enables you to run and manage multiple operating systems on a single physical server so you can save money and reduce downtime. With cloudSHIFTSM Server from mindSHIFT, you can take advantage of our expertise, facilities, and support to achieve all the benefits of virtualization, without the time, costs and resources required to deploy and maintain your own on-premises solution.
With cloudSHIFT Server, you'll reduce your physical server footprint so you can:
cloudSHIFTSM Server: On-Demand – Your own cloud server — what you need, when you need it. A cost-effective, self-service option that allows you to quickly build your own virtual servers.
cloudSHIFTSM Server: Enterprise – mindSHIFT deploys, manages and supports your organization's virtual server environment in our data centers.
mindSHIFT Cloud for IBM i: Hosted LPAR – We offer mindSHIFT cloud services specific to IBM i Power Systems (including AS/400, iSeries and System i) customers. Logical partitioning (LPAR) is an innovative approach to server management that offers the benefits and efficiencies of server consolidation without sacrificing the flexibility and scalability of maintaining separate servers. We host LPARs (HLPAR) on servers owned and maintained by us in our data centers so you can take advantage of LPAR's benefits without the hassle, time and cost of owning and maintaining your own equipment. Organizations also use mindSHIFT hosted LPARs to obtain a high-availability solution, in which a second LPAR provides backup, hot standby, load-balancing, and compliance for their primary production server.
Learn more about Managed hosting for IBM i Power Systems.
Contact mindSHIFT to learn more about mindSHIFT's cloud services.


text:
About Jeff Masters
Cat 6 lead authors: WU cofounder Dr. Jeff Masters (right), who flew w/NOAA Hurricane Hunters 1986-1990, & WU meteorologist Bob Henson, @bhensonweather
By: Dr. Jeff Masters , 11:07 AM GMT on May 22, 2012
Tropical Storm Bud intensified into a 40 mph storm this morning in the Eastern Pacific, off the coast of Mexico, and poses a significant flooding threat to the country late this week. The storm has been slow to organize due to its large size, as seen on satellite loops. But with favorable SSTs of 29 - 30°C and light to moderate wind shear in the 5 - 15 knots range expected along its path, Bud should steadily organize today and Wednesday, and become Hurricane Bud by Thursday. A trough of low pressure is expected to swing north of the storm late this week, turning Bud to the north towards the Mexican coast between Manzanillo and Acapulco. However, the trough of low pressure may not be strong enough to bring Bud ashore, and the storm could linger near the coast for several days, potentially deluging the coast with very heavy rains capable of triggering dangerous flash floods and mudslides, beginning on Friday.
Figure 1. Morning satellite image of Bud.
Record earliest date for formation of the season's second named storm
Bud is the second named storm to form in the Eastern Pacific in 2012--Tropical Storm Aletta, which formed on May 15, was the first. Bud's appearance on May 21 marks the earliest date since record keeping began in 1949 for formation of the season's second named storm. The previous record was set in 1984, when the second named storm formed on May 29. Only two other years have had two named storms in May in the Eastern Pacific--2007 and 1956, which both had the second named storm of the year form on May 30. If Bud ends up making landfall in Mexico as a hurricane, it would be only the second Eastern Pacific May hurricane on record to hit Mexico. The other was Hurricane Agatha of May 24,1971, which hit the same stretch of coast that Bud is threatening. Agatha made landfall as a Category 2 hurricane about 45 mi (75 km) from Zihuatanejo, Mexico. The village of Playa Azul was hard hit by the storm, with up to half of the village's homes destroyed. Ocean temperatures this year in the region where Aletta and Bud formed are only slightly above average, so the large scale atmospheric patterns are probably more to blame for this year's exceptionally early start to hurricane season in the Eastern Pacific.
Figure 2. True-color visible satellite image of Alberto taken by the Aqua satellite at 2 pm EDT Monday May 21, 2012. Image credit: NASA.
Alberto headed out to sea
Tropical Depression Alberto is racing northeastwards out to sea, and has been substantially weakened by very high wind shear of 50 knots and passage over cool ocean waters of 24°C (75°F). Alberto will not trouble any land areas, and does not have long to live before being completely dismantled by the high wind shear.
Figure 3. Aerial view of damage from the May 22, 2011 Joplin, Missouri tornado. Image credit: Wikipedia.
One-year anniversary of the Joplin, Missouri EF-5 tornado
May 22 marks the 1-year year anniversary of the deadly Joplin Missouri tornado. The massive EF-5 tornado with winds in excess of 200 mph mowed a 14-mile path of destruction up to one mile wide across the southern portion of the city. The tornado killed 161 people--the highest death toll from a U.S. tornado since 1947, and the seventh deadliest tornado in U.S. history. The tornado did $3 billion in damage, making it the most expensive tornado in world history. The death toll from the tornado undoubtedly would have been higher had the National Weather Service not issued a tornado warning a full 24 minutes in advance of the tornado. This is nearly double the average tornado warning lead time of thirteen minutes.
The most remarkable audio I've ever heard of people surviving a direct hit by a violent tornado was posted to Youtube by someone who took shelter in the walk-in storage refrigerator at a gas station during the Joplin tornado. There isn't much video.
Video 1. Video of the Joplin, Missouri tornado of May 22, 2011, entering the southwest side of town. Filmed by TornadoVideos.net Basehunters team Colt Forney, Isaac Pato, Kevin Rolfs, and Scott Peake.
Jeff Masters
The views of the author are his/her own and do not necessarily represent the position of The Weather Company or its parent, IBM.
Cat 6 lead authors: WU cofounder Dr. Jeff Masters (right), who flew w/NOAA Hurricane Hunters 1986-1990, & WU meteorologist Bob Henson, @bhensonweather


text:
Very sorry for your loss, prayers sent your way!
Very sorry for your loss, prayers sent your way!
"Feetdown Beatdown Razr's Edge"
Sad news today for me. Nick Jr. is gone now. He was the star of our first video ... Training a Retriever Puppy ... He was a natural ... He played his part to perfection ... He made me look so much better than I was ... No one will be able to say the right thing to me about him because no one could possibly know him the way I did.
Goodbye little pal ...
Bill Hillmann ... Caldwell, Texas
Such sad news..
Most Heartfelt Condolences to Steve, Bill..and all those that knew and loved "Nick"...
Choctaw's Daring Greatly (10/19/2015)
Choctaw's Piscataquis Sebec UD MH CGC WCX ***(All-Breed AM 2nd)
UCDX HR SR Sand Dancer's XX MTB Ranger UDT, MH, WCX **, UKC HR Finished & U-B Legs, OTCH Points, Utility B Win, Agility HIT (1/20/2001-7/24/2015)
HR SR Scarlett's Andi O'Malley CD SH OA NAJ CGC (OAJ-2 Placements) 9/16/1995-3/31/2011


text:
The Monuments Men
Based on a true story about a group of men, (older, mostly already served and were doing other jobs) who went into World War 2 to find and protect works of art and other monuments from being destroyed or kept illegally. It was performed nicely by George Clooney, Matt Damon, Bill Murray, John Goodman, Bob Balaban and a great ensemble cast. It was nice to see Bill Murray play a straight man to Bob Balaban's slightly comedic performance (usually it's the opposite).
The script may have been slow at times but history also unfolds like that. Still it is not to be missed. It's a part of World War 2 that we may have forgotten about and it's great to see that our country, and a group of men that may have not be credited correctly, were able to retrieve the world's largest collection of historical art pieces and return them to their rightful owners.
3 stars
Marc Coppola For Shelli Sonstein


text:
No concert dates found for this artist.
Add artist to my AutoNotify list
Submit Concert Information
Lauderdale Live, Huizenga Plaza, Fort Lauderdale, Fla.
John Davisson
December 7, 2013 |
Meadowbrook U.S. Cellular Pavilion, Gilford, N.H. Courtesy of Steve Pouliot
August 26, 2012 |
If we have information that is incorrect on this itinerary, please
send us an email
© Copyright 2015 Pollstar. All Rights Reserved.
Use of information on this website is subject to
License Agreement.
Tickets for dates listed may not yet be on sale. Dates may change without notice.


text:
1. Steve Madden platform sandals with that stretchy vamp.
2. John Fluevog's "Munster" shoe. Why entrusting your feet into the care of someone named "Fluevog" is beyond me.
3. Oh. No.
4. Clomp-clomp. Folks heard you coming from miles.
5. Leopard platform sandals. Did you also use those furry pens? You did, didn't you?
6. Sketchers: the worst. SO UGLYYYYAHAHHAHAHAFKDHJWLKDJF:WLEJFOW:EFIJWOEIJ.
7. Adidas unisex sport sandals. If you were a cool boy, you'd wear them with socks. All through the winter.
8. Slam your body down! (Just count on spraining your ankle.)
9. Ugh, barf.
10. Baaaaaaarrrrrffff.
11. Cookies: tossed.
12. Chunks: blown.
13. Airwalk made these shiny sneaks, and the red ones had hologram sparkles in them.
14. Vom.
15. Foam footwear. Never shoulda happened.
16. Blaahhhh.
17. Remember these Chinese-inspired Mary Janes that offered guaranteed pain thanks to no arch support?
18. Jelly high heels. Awesome at the time. Kind of embarrassing when they made a "comeback." Please no more comebacks.
19. Nike split-toe sneakers. For all those edgy weirdos.
20. Technicolor yawn.
21. Keds. A standard. Except did you ever wear two different ones on each foot? You did? Oooh, you rebel.
22. And last…technically Heelys debuted in 2000. But this was a terrible footnote on which to end the decade.
Preview Your Response
In The News Today
- France will take its first step to electing a new president today and the future of the EU could depend on the outcome 🇫🇷
- After days of deadly riots, Venezuela's president threatened protesters in bizarre video — while playing catch.
- A recent report found that 6 of the largest soft drinks companies, excluding Coca-Cola, use a combined average of just 6.6% recycled plastic.
- Frank Ocean just released a new, auto-tune inspired song called "Lens" on Blonded Radio, his Beats 1 show 🎤
Connect With RewindLike Us On Facebook Follow Us On Pinterest Follow Us On Twitter Follow Us On Apple News
Now Buzzing


text:
Brasilia as poster, vinyl, laminated, magnetic or framed wall map
Brasilia Wall Map 92 X 85 cm
Choose Map (smaller map: 92 cm or larger map 110 cm)
– Size: 92 cm (smaller side) –
with all wall maps options:
Poster, Laminated, Vinyl, Framed & Magnetic
– Size: 110 cm (smaller side)
Worldwide Free delivery on orders over € 75
Our wall map: Brasilia is sent via special cardboard tubes (posters or laminated), or framed maps. Our maps are sold to individuals and companies. Worldwide delivery. Most recommended is our Laminated Veleda (write on/wipe off over map), just from 79,50 euros
You can order in our online maps store our best options for Brasilia. From standard maps (posters), laminated maps (write on, wipe off veleda maps), to our framed maps (magnetic for magnets) or foam/cork for pins.


text:
A fine choice of properties in a beautiful region Casas da Cabreira ��" our rental agency of self-catering holiday cottages, villas and comfortable rooms in manor houses and quinta's in North Portugall.
At Oporto Excentric you can enjoy an amazing Surfcamp, with accomodation and Surf lessons together. Very close to the beach, you will feel like you were at home at the Hostel, meeting new people and enjoying some good Surfing!
Hop on a bicycle and explore Porto's historic centre with us. You will encounter an urban city towards Art and Architecture, from the Middle Ages to the Modern Era. It has never been so easy and fun to discover Porto by bike, so don't miss the opport
A program of 8 days, 7 nights (Sunday to Sunday) or 5 days, 4 nights (Sunday to Thursday) so you can fully enjoy your vacation in nature riding a beautiful Lusitano horse, breathe fresh air and return energy to your body and soul in complete harmony
Staying in a friendly Hostel with all comfort and a relaxed atmosphere. Get to know Oporto City, with its beautiful beaches, landscapes, monuments, great food and nice people. Learn to surf with the best teachers. Open from 1 April to 30 October.
No matter if you're a beginner wanting to learn to surf or simply wish to explore the many high class surf spots in the region, Surfivor Surf Camp has the right package for you.
This is a unique MTB tour in Portugal. The challenging seven day track will allow the in depth discovering of an often forgotten Portugal nested between these mountains and away from the bustle of big coastal cities.
A gorgeous tour which takes you to several Manor Houses, Palaces and Monasteries; these magnificent places were once inhabited by the clergy or the Queens and Kings of Portugal and now are converted into exquisite lodgings, which we call POUSADAS.
Arcozelo, Portugal visitors guide to accommodations, adventure travel, unique tours and rentals. Check out top Arcozelo, Portugal getaways & destinations. Arcozelo, Portugal vacations, packages & travel spots. Visit Arcozelo, Portugal !.


text: What Earl said. Plus, when you train, shoot a lot of long bird singles, with the short bird out - so that the dog understands that he may not get a short bird. Also, shoot flyer at long station - maybe use a big white chicken. Make the long bird exciting.


text:
- Sort:
- Most Popular | Most Recent
This frame is an example of American Foulbrood disease which is highly transmittable and one of the most destrucitve and widespread brood diseases. It is very difficult to treat and if it does not kill a colony it will seriously weaken it. Paenibacillus larvae, the cause of AFB, only affects brood two days and younger....
On the final day of the healthy bee frame much of the capped brood has emerged and the young brood is beginning to mature. The honey pattern has changed once again. If you look carefully you can once again see the new workers emerging though not as many as in the day before.
In day seven of the progression image many of the larvae have emerged. The honey pattern is slightly less than the previous day and there is a higher amount of uncapped brood. If you look closely you can see worker bees emerging. When I brought the frame into the lab, there were only two bees crawling around on it, how...
Day 6 of the healthy bee frame shows that almost all mature larvae have been capped and that new brood are beginning to grow. The capped honey cells are slightly different than before.
This frame contains a bee disease known as Chalkbrood. This disease is fairly common and affects the bees at the larval stage, killing brood in a matter of 2 days once they are capped. It will not kill a colony but it will weaken it. Notice the spotty brood pattern which is a sign of an unhealthy colony.
I took this panorama while some friends and I jumped off of the cliffs of the canyon into the Big Chco Creek. There are several swimming holes in Upper Bidwell Park and when temperatures soar over 100 degrees F its one of many places people take refuge from the heat. Mike Andree
On day 5 of the healthy bee frame progression there is less open brood due to the dillegence of the worker bees.
This is day four of the healthy bee frame progression. As you can see, the frame has not changed drastically over the weekend although it does look slightly different than before. Many of the cells filled with pollen in the previous images are no longer and there are higher amounts of uncapped brood cells present.
On day three of the prgression image all the drone cells have hatched. The pollen formation has changed slightly and there is also small difference in the capped honey cell formation.


text:
Toggle: English / Spanish
Zinc oxide is an ingredient in many products, including certain creams and ointments used to prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone accidentally or intentionally eats this medication.
This is for information only and not for use in the treatment or management of an actual poison exposure. If you have an exposure, you should call your local emergency number (such as 911) or the National Poison Control Center at 1-800-222-1222.
See also: Bacitracin zinc overdose
Desitin overdose; Calamine lotion overdose; Zinaderm overdose; Amalox overdose; Azo 22 overdose
Zinc oxide
Zinc oxide may be found in many different products, including:
Note: This list may not be all-inclusive.
If the person swallowed a lot of zinc oxide, immediately give the person water or milk. Do NOT give water or milk if the patient is vomiting or has a decreased level of alertness.
If the chemical is on the skin or in the eyes, flush with lots of water for at least 15 minutes.
If the chemical is breathed in (inhaled), move the person to fresh air.
Call your doctor or poison control.
Determine the following information:
The National Poison Control Center (1-800-222-1222) can be called from anywhere in the United States. This national hotline number will let you talk to experts in poisoning. They will give you further instructions.
This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.
Take the container with you to the hospital, if possible.
See: Poison control center - emergency number
The health care provider will measure and monitor the patient's vital signs, including temperature, pulse, breathing rate, and blood pressure. Symptoms will be treated as appropriate.
Zinc oxide is not very toxic (poisonous) when you mistakenly eat it. Most of the harmful effects come from breathing in the gas form of zinc oxide at industrial sites in the chemical industry. This leads to a condition known as "metal fume fever." Metal fume fever involves a metallic taste in the mouth, fever, headache, chest pain, shortness of breath, and other symptoms, which suddenly start about 4 to 12 hours after exposure.
Either way, long-term recovery is very likely.
Holland MG. Pulmonary toxicity. In: Shannon MW, Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose. 4th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 9.
Hall AH, Shannon MW. Other heavy metals. In: Shannon MW, Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose. 4th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 75.
A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch)
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- 2013 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.


text:
Nox-Audio Scout HSM001A0 Headset (Black)
" Now, I recall reading CNET's review on the much overpraised "Nox Audio Scout's" this is what originally made me want to get a pair of these in ears and I have to say, they do have an interesting design. The flanges or rubber pieces on the side of the headphones may look nice or helpful but be warned! they are nothing more than a useless nuisance that gets in the way whenever you try to..." --OmarSy
Phillips SHN2500: Active Noise Canceling Earbuds
Philips Noise cancel earbuds active noise reduction cuts out the background noise that spoils the listening pleasure and delivers pure sound on the move. Slip in these comfortable noise-canceling earbud headphones and let the outside world melt away. These earbuds combine high-quality sound with cutting-edge, 10-db noise-reduction technology. Planes, trains and busy offices fade out as the...


text:
What's also fun, really fun, for me - is to talk about training methods to get the dog to do what he does.
Today, we had a City Police officer and a County Deputy Sherrif both. One handled the dog, the other spoke, and we had a couple assistants do their thing.
The speaker spent a good bit of time discussing HOW they train the dog to do what they do. What was so darn cool to me, was how they break it all down into such basic, simple elements that are so elementary they are brilliant! Then they take those elements and chain them together. It is just like the way we train a dog to handle or other things in our game!
It is really amazing.
The more I'm around this stuff, the more I realize that a good dog person is a good dog person.
I agree.
I remember a time when I was phase 2 when I did not respect things like agility. Now I am fascinated by how anyone trains a dog to do anything. For example: Weave pole. That zigzag pattern among a row of white PVC pipes.... It is amazing how they teach dogs to do that.
How to teach a dog to follow a scent trail to catch a bad guy. So elementary, it is brilliant!
Another cool thing. There is frequently method A, B, or C. One thing I'm learning is to not BASH B or C if you do A. Why? Because one day, you may have a dog who requires one of the other methods. Why else? Because usually, no matter how big, how bad, how awesome you are, there is someone else who is bigger and badder. And sometimes they got there using method B or C.
You really gotta be careful about how high a pedestal you put your method, your accomplishments, your dog on. There's usually someone who's done more, somewhere. And they may have used a different method than you did!
It's all good.


text:
Latest Headlines
WHAT IT MEANS: December 5, 2010
Posted on 5 Dec 2010 by Jeremy Schilling.
Here's this week's What It Means after a fantastic Sunday outside of LA: Graeme McDowell Beating Tiger Woods at the Chevron World Challenge: What more can you say? GMac has put himself up in the top echelon of golfers in 2010, once again proving that he can beat the best on the biggest stage. Most impressive to me was the bogey on 17. After hitting it in the hay behind the green, he took an un...


text:
The centre court didn't get its British champion, it didn't have any healing of the 76-year-old wound, but it was maybe not the worst of fates.
It just had to go on sharing the champion of the world, the player who is nominally Swiss but above all the property of any nation that can rise up and salute the kind of talent that crosses all borders as though they do not exist.
This may not be the cure-all for the pain of Andy Murray, who could not be challenged for a second when he declared that he put in by far his best performance of four Grand Slam final appearances, but for Roger Federer, the man who breaks records and hearts with supreme artistry and a natural-born winning instinct, there was still another reward for quite unprecedented consistency, in the form of a 4-6 7-5 6-3 6-4 victory.
When the rain forced on the centre court roof, it meant that Federer's forensically precise game would make Murray's dream of being the first home-grown player to win the title since 1936 even more remote.
Murray fought on with character and spirit, but he knew he was in the grip of something close to a force of nature.
It was a brilliant final in so many ways, so luminously expressing the finest quality of two deeply talented players that it had to be rated the best since 2008.
If that sounds like mild praise we just have to remember that the one four years ago was arguably the greatest of all time. It was also deemed historic because it seemed to signal the end of Federer's finest days, the passing of the time when he could go out and explain to a ferocious young challenger like Rafael Nadal some of the most deadly nuances of the game.
Four years on, Federer is suggesting he has made some kind of deal with fate and the passing of the years.
Murray could hardly have played better, more intelligently or with better discipline. He played shots that were sublime. He fought, he scuffled and for more than three hours he consigned the memory of a superbly gifted but self-indulgent nearly man to another lifetime.
He was, to put it another way, a credit to the old champion Ivan Lendl, who has brought a new aura of hard-nosed professionalism to the Murray camp.
Murray's campaign died, effectively, in the sixth game of the third set. He went into it 2-3 with service, fighting with all the edge and touch that had carried the first set with a confidence that had ambushed Federer.
Not only had Federer surrendered that opening set, he had been made to look tentative and now Murray, though no doubt smarting over missed opportunities in the second set, had every reason to believe that he could regain a winning momentum. It was a belief reinforced by an easy march to 40-0, a position of strength that came in the wake of an extraordinary backhand passing shot which left Federer stunned for at least a moment.
In fact, it had the effect of concentrating his mind. What followed was tennis superbly on the edge. Murray had seven game points. There were 10 deuces and it was on the seventh break point that Federer turned the match, gave himself an edge that he never looked likely to surrender. There were times when Federer's extraordinary skill threatened to utterly engulf his opponent.
But Murray was simply not for disintegration, at least not until the final stages of the fourth set when all the world knew that Federer was about to draw level with Pete Sampras on the mark of seven Wimbledon wins - and move to his 17th Grand Slam triumph, the champion of champions.
When the wounds have healed Murray will be able to tell himself that he did all he could.
- Independent


text:
Spider "realvoice" Vertical in the Ear Headphone
" First off the disclaimer, the Realvoice IEM'S were given to me a month or two back for reviewing. I would like to thank Spider Cable for the review sample and my apologies for taking so long in writing this review. Since I have had these I have used them about 75% of the time when I am using earphones, which probably averages about two hours per day. So I have put quite a few hours..." --Carlsan
Lenntek Pro Series with Balanced Armature Professional In-ear Monitor (IEM)
"My Altec Lansing 716s are getting old and my Sennheiser HD 600s will need new cords shortly, so when I saw the Lenntek Pros at Costco.com for $50, I couldn't pass them up. When I first opened the box, and cut open the sealed all around plastic, I noticed that the included tips are all very small. But if you push them deep, deep, deep into your your ear canal you can get a seal...." --chasfs