Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial. Quality of care for secondary prevention for patients with coronary heart disease: results of the Hastening the Effective Application of Research through Technology (HEART) trial. Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient. Physiologic and related behavioral outcomes from the Women's Lifestyle Heart Trial. Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease.
The use of repeated intravenous infusions of EDTA, which has become known as "chelation therapy," has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication.
                A double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal proportion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%).
                Chelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication. Effective therapies for reducing mortality rates in persons with coronary heart disease (CHD) remain underused. We report the results of an effectiveness trial of a quality improvement effort to increase the use of 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors in patients with CHD in a network-model managed-care setting.
                Patients with CHD were identified by searching a claims database. The use of therapies was assessed by linkage with a pharmacy database. An intervention, consisting of a guideline summary, peer comparison performance feedback, and patient specific chart reminders was evaluated in a randomized, practice-based effectiveness trial.
                Data were available for >700 patients per year (1999-2002) in 131 practices. At baseline (1999), 55% of patients were receiving HMG CoA reductase inhibitors, 39% of patients were receiving beta-blockers, and 24% of patients were receiving ACE inhibitors. The use of all 3 types of medications increased steadily with time, with the exception of a decrease in the use of HMG CoA reductase inhibitors in the final year (2002). No difference in medication use was observed between randomized groups.
                The observed pattern of care supports the contention that the quality of outpatient care for secondary prevention of CHD improved from 1999 to 2002 in this setting. The basis for the inconsistent pattern of use of HMG CoA reductase inhibitors is not certain, but may relate to concerns about toxicity. Centralized mailings of guideline summaries, performance feedback reports, and chart reminders had no observable impact on quality of care in this setting. More intensive intervention may be required to improve the quality of outpatient care for the secondary prevention of CHD. In patients after renal transplantation functional arterial vessel wall properties are impaired. Whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have a sustained effect on endothelial function and arterial distensibility in patients after renal transplantation is not clear. The authors studied the effects of a long-term therapy with fluvastatin on large artery distensibility and flow-mediated vasodilation (FMD) in hypercholesterolemic patients after renal transplantation in a prospective, blinded, and randomized trial.
                Twenty-six patients who had undergone renal transplantation were assigned randomly to either fluvastatin, 40 mg/d (n = 13) or placebo (n = 13) and underwent follow-up for 3 years. At baseline and after 6, 12, and 36 months of treatment, carotid and brachial artery distensibility, endothelium-dependent FMD, and nitroglycerine-induced vasodilation (NMD) of the brachial artery were measured by a echo-tracking device.
                A significant decrease in total and low-density cholesterol was observed after 6, 12, and 36 months in patients treated with fluvastatin but not in the placebo group. FMD increased with fluvastatin from 4.6 +/- 2% to 12.4 +/- 2% after 12 months; this improvement was sustained with 13.4 +/- 3% after 36 months (P < 0.05). However, placebo did not alter FMD (P < 0.001 for trend difference between groups by analysis of covariance). Endothelium-independent NMD was similar in both groups at baseline and during therapy. Neither carotid nor brachial artery distensibility coefficients were altered by either treatment.
                HMG-CoA reductase inhibitor therapy over 3 years results in a significant and sustained improvement of endothelial function in hypercholesterolemic patients after renal transplantation. However, this is not accompanied by a beneficial effect on impaired large artery distensibility even after long-term therapy with fluvastatin. The Women's Lifestyle Heart Trial was a small (N = 28) randomized controlled trial to evaluate the effects of a comprehensive lifestyle self-management program (very low-fat vegetarian diet, stress-management training, exercise, group support, and smoking cessation) on reduction of cardiovascular risk factors in postmenopausal women with coronary heart disease (CHD). Women assigned to the treatment condition (Prime Time) participated in a week-long retreat followed by twice-weekly 4-hour meetings. Endpoints were program adherence; changes in lipid profiles, body mass, blood pressure, hypolipidemic and antihypertensive medications; and quality of life. Risk factor and psychosocial evaluations were conducted at baseline and at 4, 12, and 24 months. Repeated measures analyses of covariance revealed that the dietary, stress management, and physical activity changes made by intervention women were dramatic and lasting. There were significantly greater improvements in the Prime Time condition compared to the usual care control group on body mass, angina symptoms, and quality of life, and a tendency for a greater reduction in blood pressure-lowering medications. Similar patterns were seen in lipids, blood pressure, and lipid-lowering medications, but did not reach significance. These results demonstrate that postmenopausal CHD women can make lasting lifestyle changes, and that these changes may reduce the need for cardiac medications and improve CHD risk factors and quality of life. A prospective, randomized, controlled clinical trial in patients with coronary artery disease (CAD) and a concurrent physical disability evaluated the effects of a home exercise training program on cardiovascular function and blood lipids. Eighty-eight men between the ages of 42 and 72 years (mean 62) with documented CAD and a physical disability with functional use of > or = 2 extremities including 1 arm were randomized to either a 6-month home exercise training program using wheelchair ergometry or to a control group that received usual and customary care. Both groups received dietary instructions and were requested to follow a fat-controlled diet. Exercise test variables with echocardiography and blood lipids were measured at baseline and at 6 months. The home exercise training group significantly improved both peak exercise left ventricular ejection fraction (p = 0.007) and fractional shortening (p = 0.01) between baseline to 6 months, whereas the control group showed no significant changes. Exercise training effects of decreased resting heart rate (p = 0.03) and decreased peak rate pressure product (p = 0.03) were also found in the treatment group. No exercise-related cardiac complications occurred. Both groups significantly (p < or = 0.01) increased high-density lipoprotein cholesterol levels. These results indicate that physically disabled men with CAD can safely participate in a home exercise training program which may result in intrinsic cardiac benefits. The metabolic cost of activities of daily living imposed on this disabled population may also have a positive effect on high-density lipoprotein cholesterol levels.
At present, there is insufficient evidence to decide on the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. This decision must be preceded by conducting randomized controlled trials that would include endpoints that show the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.