coronary heart disease is the leading cause of death globally , with myocardial infarction a common manifestation of this disease . it is estimated that there are about 230 million people in china with cardiovascular disease , including 200 million with hypertension , 7 million with stroke , 2 million with myocardial infarction , and 4.2 million with heart failure . a study in china in 2008 indicated that the mortality rate of coronary heart disease in urban residents was about 91.41 per 100 000 , compared with 51.89 per 100 000 in rural residents . in recent years patients with st - segment elevation myocardial infarction ( stemi ) require urgent revascularization as well as aggressive antiplatelet and antithrombotic pharmacotherapy . if these most appropriate treatments are offered within the shortest possible time from symptom onset , it will dramatically improve clinical outcome compared with conservative treatment strategies . unfortunately , only a minority of patients receive all guideline - indicated therapies within the recommended timeframes , which leads to some unacceptably long delays to treatment reported in real - world registries . primary percutaneous coronary intervention ( ppci ) is the preferred reperfusion strategy for stemi when performed within 90120 min from the first medical contact and performed by a person skilled in the procedure . however , many hospitals do not have resources to provide ppci for patients , thus a large proportion of stemi patients are transferred for ppci in bigger hospitals , which leads to substantial time delays to reperfusion compared with the patients who receive on - site fibrinolytic therapy [ 68 ] . transferring for ppci involves a longer delay to treatment , which leads to a potential loss of benefit , compared with receiving iht in the local county hospital . from the patient s perspective , the delay between symptom onset and provision of reperfusion therapy ( either starting fibrinolysis or transferring for ppci ) is possibly the most important , since it reflects total ischemic time . thus , there is a need to understand the effect of treatment delays associated with duration of transfer from inpatient contact through inter - hospital transfer for ppci with respect to patient survival . as for the geographical and traffic limitations in our area , the stemi patients with time from symptom onset to ihfmc 36 h accounts for approximately 40% of stemi patients in our hospitals . therefore , the primary objective of this study was to investigate differences in 30-day and 1-year mortality of stemi patients whose time from symptom onset to in - hospital first medical contact ( ihfmc ) was 36 h who received iht in a local county hospital vs. those treated with ppci via inter - hospital transfer to the emergency cardiac center of henan province people s hospital . the study was designed to compare the prognosis and survival of stemi patients who received iht with those who declined iht and opted for inter - hospital transfer for ppci and thus having longer time to treatment . from january 2012 to january 2013 , 998 patients were identified as stemi patients after screening from 6 county hospitals affiliated to zhengzhou city . of these , stemi patients with symptom onset to ihfmc beyond 3 h but within 6 h were enrolled in the study . these patients either received iht in the local county hospital or they rejected iht and were brought to the pci center within 3 h for ppci ( figure 1 ) . a total of 653 patients were excluded from the study because symptom onset to ihfmc was less than 3 h or more than 6 h. in total , 332 patients met the 36 h criterion , of whom 13 were excluded because they had contraindications for iht or refused to receive iht and were transferred for ppci . a total of 333 stemi cases were taken up for the analysis , comprising 192 patients in the iht group and 141patients in the transferred ppci group . patients with stemi were defined as having continuous ischemic symptoms for at least 30 min with the following electrocardiographic changes : st - segment elevation 2 mm in 2 continuous precordial leads or 1 mm in 2 limb leads , extensive st - segment depression in the precordial leads representing posterior myocardial infarction with confirmatory posterior circulation infarction , and subsequent cardiac enzyme ( troponin or ck - mb ) elevation > 2-fold of the normal upper limit . symptom onset was defined as the time observed by the patient or bystanders of the onset of the presenting symptoms ( e.g. , chest pain , dyspnea , cardiac arrest ) . first medical contact ( fmc ) was defined as when the paramedics arrived . in - hospital first medical contact ( ihfmc ) was defined as the time when in - hospital doctors were at the patient s side . we identified several time points during the process : symptom onset , first medical contact , ihfmc , diagnosis , providing consent , start of therapy , and reperfusion time . five time periods were recorded : time from symptom onset to first medical contact was recorded as period 1 ; time from first medical contact to diagnosis was recorded as period 2 ; time from diagnosis to providing consent was recorded as period 3 ; time from providing consent to beginning of treatment was recorded as period 4 ; and time from beginning time of treatment to patency was recorded as period 5 . the demographic data , transfer modality , time segments , clinical status , and in - hospital outcomes in both patient groups were prospectively recorded . details related to reperfusion procedures and 30-day and 1-year survival were tracked prospectively in all the referring county hospitals and the emergency cardiac registry of henan provincial people s hospital . this study was conducted after approval from the ethics committee of henan province people s hospital . categorical data are represented with frequencies and percentages and were analyzed by chi - square tests . continuous variables are described as mean sd or median and interquartile range , and were analyzed by the t test or wilcoxon rank - sum test . to examine the association of treatment strategy and mortality , multivariate logistic regression was used to assess its relation with 30-day mortality , and its relation with 1-year mortality was assessed by the cox proportional hazards model . covariates significantly associated with mortality in univariate analysis were considered in the multivariable logistic regression analysis and the cox proportional hazards model . all p values were 2-tailed , and a p value < 0.05 was considered significant . the study was designed to compare the prognosis and survival of stemi patients who received iht with those who declined iht and opted for inter - hospital transfer for ppci and thus having longer time to treatment . from january 2012 to january 2013 , 998 patients were identified as stemi patients after screening from 6 county hospitals affiliated to zhengzhou city . of these , stemi patients with symptom onset to ihfmc beyond 3 h but within 6 h were enrolled in the study . these patients either received iht in the local county hospital or they rejected iht and were brought to the pci center within 3 h for ppci ( figure 1 ) . a total of 653 patients were excluded from the study because symptom onset to ihfmc was less than 3 h or more than 6 h. in total , 332 patients met the 36 h criterion , of whom 13 were excluded because they had contraindications for iht or refused to receive iht and were transferred for ppci . a total of 333 stemi cases were taken up for the analysis , comprising 192 patients in the iht group and 141patients in the transferred ppci group . patients with stemi were defined as having continuous ischemic symptoms for at least 30 min with the following electrocardiographic changes : st - segment elevation 2 mm in 2 continuous precordial leads or 1 mm in 2 limb leads , extensive st - segment depression in the precordial leads representing posterior myocardial infarction with confirmatory posterior circulation infarction , and subsequent cardiac enzyme ( troponin or ck - mb ) elevation > 2-fold of the normal upper limit . symptom onset was defined as the time observed by the patient or bystanders of the onset of the presenting symptoms ( e.g. , chest pain , dyspnea , cardiac arrest ) . first medical contact ( fmc ) was defined as when the paramedics arrived . in - hospital first medical contact ( ihfmc ) was defined as the time when in - hospital doctors were at the patient s side . we identified several time points during the process : symptom onset , first medical contact , ihfmc , diagnosis , providing consent , start of therapy , and reperfusion time . five time periods were recorded : time from symptom onset to first medical contact was recorded as period 1 ; time from first medical contact to diagnosis was recorded as period 2 ; time from diagnosis to providing consent was recorded as period 3 ; time from providing consent to beginning of treatment was recorded as period 4 ; and time from beginning time of treatment to patency was recorded as period 5 . the demographic data , transfer modality , time segments , clinical status , and in - hospital outcomes in both patient groups were prospectively recorded . details related to reperfusion procedures and 30-day and 1-year survival were tracked prospectively in all the referring county hospitals and the emergency cardiac registry of henan provincial people s hospital . this study was conducted after approval from the ethics committee of henan province people s hospital . categorical data are represented with frequencies and percentages and were analyzed by chi - square tests . continuous variables are described as mean sd or median and interquartile range , and were analyzed by the t test or wilcoxon rank - sum test . to examine the association of treatment strategy and mortality , multivariate logistic regression was used to assess its relation with 30-day mortality , and its relation with 1-year mortality was assessed by the cox proportional hazards model . covariates significantly associated with mortality in univariate analysis were considered in the multivariable logistic regression analysis and the cox proportional hazards model . all p values were 2-tailed , and a p value < 0.05 was considered significant . all data were analyzed using spss 16.0 software ( spss inc . , chicago , usa ) . the baseline characteristics and demographic data ( age , sex , smoking , hypertension , diabetes , and dyslipidemia ) of the 2 groups are presented in table 1 . although the patients in the inter - hospital transfer group tended to be older and male with a past history of transient ischemic attack or stroke , the differences were not statistically significant . similar patterns with regard to cardiovascular risk factors , diabetic status , cardiovascular history , territory of stemi , and number of diseased vessels were observed in both groups . no significant difference was observed in the number of patients complicated with cardiac arrest requiring ventilation , congestive heart failure , or cardiogenic shock . no significant difference was observed between the 2 groups in the symptom - to - ihfmc time ( 26552 vs. 27152 min , p=0.288 ) and diagnosis time ( 15.03.0 vs. 14.93.1 min , p=0.713 ) ( table 2 ) . in the iht group , time of providing consent , preparation time , and time from beginning of iht to patency were 6817 min , 235 min , and 608 min , respectively . the mean transport time from the primary county to the key hospital for ppci was 12436 min . in the inter - hospital transfer group , the time from admission to consent for ppci , ppci preparation time , and time from beginning of ppci to patency were 3011 min , 206 min , and 4515 min , respectively . no significant difference was seen in the total ischemic time between the inter - hospital transfer group ( 45263 min ) and the iht group ( 48367 min ) . reperfusion was achieved in 139 patients ( 139/192 , 72.4% ) in the iht group , while in the ppci group , 136 patients achieved reperfusion ( 136/141 , 96.5% ) . the complications of patients in the 2 groups were as follow . among 192 patients in the iht group , 4 patients had fatal bleeding symptoms ( 2 were cerebral hemorrhage and 2 were upper gastrointestinal bleeding ) , 2 patients had stroke symptom ( cerebral bleeding ) , and 2 patients had reinfarction symptom . among 141 patients in the ppci group , 3 patients had fatal bleeding symptoms ( 1 was retroperitoneal hemorrhage , 1 was cerebral bleeding , 1 was upper gastrointestinal bleeding ) , 1 patient had stroke ( cerebral bleeding ) , 1 patient had stent thrombosis symptoms , 1 patient had coronary dissection tear symptoms , and no patients had reinfarction symptoms . the all - cause mortality in the iht group and inter - hospital transfer group with ppci at 30 days ( 13.0% vs. 9.9% , p=0.386 ) were not significantly different . however , mortality in the iht group and inter - hospital transfer group with ppci at 1 year showed a significant difference ( 23.4% vs. 14.1% , p=0.035 ) ( figure 2 ) . survival curves between the iht group and inter - hospital transfer group with ppci for 30 days showed no significant difference because the divergence level was low ( figure 3 ) . however , differences in survival curves between the iht group and inter - hospital transfer group with ppci for 1 year showed significant differences , with higher divergence level ( figure 4 ) . overall , the patients undergoing ppci , even with inter - hospital transfer , had higher survival rate for 1 year compared with patients receiving iht . multivariate analysis of the factors associated with the mortality at 30-day and 1-year mortality are shown in tables 3 and 4 . according to the results of the multivariate analysis , we used univariate analysis to reveal univariate predictors for 30-day and 1-year mortality after st - segment elevation mi ( tables 5 and 6 ) . cardiogenic shock and cardiac arrest requiring ventilatory support were the 2 strongest predictors for mortality in this population at 30 days and 1 year . importantly , prior tia or stroke remained a significant factor associated with mortality at 30 days ( or : 8.8 , 95% ci : 2.926.7 , p<0.001 ) and at 1 year ( or : 14.2 , 95% ci : 3.339.7 , p=0.000 ) . left ventricular ejection fraction ( 40% ) ( or : 4.3 , 95% ci : 2.111.4 , p=0.004 ) and prior history of myocardial infarction ( or : 1.7 , 95% ci : 1.03.2 , p<0.001 ) were still independent predictors for lower mortality at 30 days but not at 1 year . inter - hospital transfer time for ppci was an independent predictor for survival ( or : 4.4 , ci 95% : 1.914.5 , p=0.001 ) . no significant difference was observed between the 2 groups in the symptom - to - ihfmc time ( 26552 vs. 27152 min , p=0.288 ) and diagnosis time ( 15.03.0 vs. 14.93.1 min , p=0.713 ) ( table 2 ) . in the iht group , time of providing consent , preparation time , and time from beginning of iht to patency were 6817 min , 235 min , and 608 min , respectively . the mean transport time from the primary county to the key hospital for ppci was 12436 min . in the inter - hospital transfer group , the time from admission to consent for ppci , ppci preparation time , and time from beginning of ppci to patency were 3011 min , 206 min , and 4515 min , respectively . no significant difference was seen in the total ischemic time between the inter - hospital transfer group ( 45263 min ) and the iht group ( 48367 min ) . reperfusion was achieved in 139 patients ( 139/192 , 72.4% ) in the iht group , while in the ppci group , 136 patients achieved reperfusion ( 136/141 , 96.5% ) . the complications of patients in the 2 groups were as follow . among 192 patients in the iht group , 4 patients had fatal bleeding symptoms ( 2 were cerebral hemorrhage and 2 were upper gastrointestinal bleeding ) , 2 patients had stroke symptom ( cerebral bleeding ) , and 2 patients had reinfarction symptom . among 141 patients in the ppci group , 3 patients had fatal bleeding symptoms ( 1 was retroperitoneal hemorrhage , 1 was cerebral bleeding , 1 was upper gastrointestinal bleeding ) , 1 patient had stroke ( cerebral bleeding ) , 1 patient had stent thrombosis symptoms , 1 patient had coronary dissection tear symptoms , and no patients had reinfarction symptoms . the all - cause mortality in the iht group and inter - hospital transfer group with ppci at 30 days ( 13.0% vs. 9.9% , p=0.386 ) were not significantly different . however , mortality in the iht group and inter - hospital transfer group with ppci at 1 year showed a significant difference ( 23.4% vs. 14.1% , p=0.035 ) ( figure 2 ) . survival curves between the iht group and inter - hospital transfer group with ppci for 30 days showed no significant difference because the divergence level was low ( figure 3 ) . however , differences in survival curves between the iht group and inter - hospital transfer group with ppci for 1 year showed significant differences , with higher divergence level ( figure 4 ) . overall , the patients undergoing ppci , even with inter - hospital transfer , had higher survival rate for 1 year compared with patients receiving iht . multivariate analysis of the factors associated with the mortality at 30-day and 1-year mortality are shown in tables 3 and 4 . according to the results of the multivariate analysis , we used univariate analysis to reveal univariate predictors for 30-day and 1-year mortality after st - segment elevation mi ( tables 5 and 6 ) . cardiogenic shock and cardiac arrest requiring ventilatory support were the 2 strongest predictors for mortality in this population at 30 days and 1 year . importantly , prior tia or stroke remained a significant factor associated with mortality at 30 days ( or : 8.8 , 95% ci : 2.926.7 , p<0.001 ) and at 1 year ( or : 14.2 , 95% ci : 3.339.7 , p=0.000 ) . left ventricular ejection fraction ( 40% ) ( or : 4.3 , 95% ci : 2.111.4 , p=0.004 ) and prior history of myocardial infarction ( or : 1.7 , 95% ci : 1.03.2 , p<0.001 ) were still independent predictors for lower mortality at 30 days but not at 1 year . inter - hospital transfer time for ppci was an independent predictor for survival ( or : 4.4 , ci 95% : 1.914.5 , p=0.001 ) . previous studies demonstrated that ppci was superior to thrombolysis in terms of reinfarction , stroke , and death . however , these advantages may be lost due to the delay of treatment when transporting patients to a primary percutaneous coronary intervention center . time to treatment is a key factor for survival , not only for thrombolysis therapy but also for primary angioplasty . in this study , we retrospectively analyzed stemi patients with symptom onset to ihfmc beyond 3 h but within 6 h who received iht in the local county hospital and compared them to those who accepted inter - hospital transfer for ppci in henan province , china . patients who received iht in the local county hospital or ppci after inter - hospital transfer had similar patterns of cardiovascular risk factors , past cardiovascular history , diabetic status , number of diseased vessels , and territory of stemi . there were no differences in number of cases complicated by cardiac arrest requiring ventilatory support , congestive heart failure , and cardiogenic shock between the 2 groups . the bleeding complication rate was higher in the iht group than in the ppci group . in the iht group , there were 4 patients with fatal bleeding and 13 patients with nonfatal bleeding ( e.g. , gums bleeding , small hemoptysis , nasal bleeding , and urinary and reproductive tract bleeding ) , and in the ppci group there were 4 patients with fatal bleeding and 4 patients with nonfatal bleeding ; the rate was 8.9% in the iht group and 5.0% in the ppci group . patients undergoing ppci in the inter - hospital transfer group had a higher survival rate at 1 year compared with patients receiving iht , but no significant difference was found at 30 days . the outcome of the 2 treatment strategies had no significant difference at 30 days , mainly because complications in the 2 groups were similar . in addition , both treatments guarantee blood perfusion , and the patients were mostly convalescing and resting , so the survival outcomes were not significantly different . however , with increasing activity over time , patients who received ppci treatment had better activity endurance than the patients treated with iht . the recurrence rate of angina pectoris or myocardial infarction of patients in the ppci group was lower than that in the iht group . thus , 1-year outcomes in the ppci treatment group were better than in the iht group . to the best of our knowledge , this is the first time that ppci involving inter - hospital transfer has been shown to be an independent predictor for survival after stemi . in treating patients with stemi , ppci is more commonly used than iht . according to north american and european guidelines ( class ia ) , primary pci should be preferred to thrombolysis , provided that patients undergo pci within 120 min of first medical contact . a prospective cohort study reported that , compared with iht and pht , ppci was associated with reduced duration of hospital stay , reinfarction , and mortality in 26 205 patients with stemi . similar results have also been reported in other studies , although not in all registry studies [ 1315 ] . these results are also consistent with the results of other studies   and the danish trial in acute myocardial infarction , showing that ppci has a better outcome than thrombolysis in terms of delay times of up to at least 34 h. consistent with the results of several previous reports , our study found that the effects of reperfusion treatment depend on the treatment delay , but the loss in benefit with longer delay is less obvious and appears later with ppci than with thrombolysis . in some cases , post - procedural bleeding events were associated with an increased risk of in - hospital mortality in pci , and an estimated 12.1% death rate related to bleeding complications occurs in the u.s . new antithrombin therapy has been shown to reduce periprocedural bleeding after ppci , and the radial approach in ppci was associated with a significantly lower incidence of major bleeding . although patients in the inter - hospital transfer group were older ( 61.311.6 years ) , more likely to be male , and have a history of transient ischemic attack or stroke , the overall 1-year survival rate for ppci was higher than with iht . in the senior pami trial , 481 patients who were older than 70 years and who had stemi ( > 12 h of symptoms ) were randomly divided to pci versus fibrinolytic therapy . results demonstrated a 36% reduction in death or nonfatal stroke ( 11.3% pci vs. 13% thrombolytic therapy , p=0.57 ) , while a significant 55% reduction in death , stroke , or reinfarction favoring pci ( 11.6% pci vs. 18% thrombolytic therapy , p<0.05 ) was observed . inter - hospital transfer time for ppci was an independent predictor for survival ( or : 4.4 ci 95% : 1.914.5 , p 0.001 ) in the present study , and shows that ppci is a better treatment for these patients . however , other studies in which stemi patients with a treatment strategy of emergency aggressive reperfusion therapy with primary pci showed that more patients in the traditional inter - hospital transfer died during the first year after the event , and this may be related to the long symptom - to - balloon time . in another regional stemi program using a contemporary primary pci strategy , patients who were transferred directly to the pci center via pre - hospital triage strategy had a significantly lower mortality at 30 days and at 1 year when compared with inter - hospital transfer patients . the authors indicated that a direct transfer strategy is an independent predictor for 1-year survival after stemi when considering other important risk factors , including patient age , left ventricular ejection fraction , pre - hospital cardiac arrest , and cardiogenic shock . our study confirms that cardiogenic shock , cardiac arrest requiring ventilation , and prior tia or stroke were the strongest predictors for mortality in this population at 30 days and 1 year . another 2 factors  prior history of myocardial infarction and left ventricular ejection fraction  are also independent predictors for lower mortality at 30 days but not at 1 year . findings of our study suggest that , in the present economic and medical circumstances in henan province , china , patients with stemi generally arrive at local hospitals without a pci center after a relatively long time , so transfer ppci would be a better alternative . , we recommend reinforcing public health education , expanding scientific knowledge , enhancing medical skill and technique of medical staff , and setting up extensive emergency rescue systems . establishing and maintaining interactive affiliations among the county hospitals , municipal hospitals , and provincial hospitals through mobile networks or interactive communication equipment will help provide better patient care . all these problems should be solved through deepening the healthcare reform and improving the doctor - patient relationships and the quality of medical technology . thus , based on china s national conditions , it is not currently possible to use the door - to - balloon time . therefore , some revisions of china s stemi guidelines should be made to improve actual working conditions in various aspects , including the clinical , research , and policy formulation in this field , just to meet the requirements of this specialty . as this was not a randomized controlled study , there could have been selection bias in patient assignment to groups . this study aimed to investigate the reperfusion time of patients with stemi in a definite time period only performed in a few county hospitals in henan province . our results may have been affected by cultural , geographical , medical resources , and economic conditions . overall , the primary percutaneous coronary intervention time of stemi patients was likely to be longer than that in developed countries , mainly due to pre - hospital delay , inter - hospital transfer time , consent delay , and medical cost delay . as this was not a randomized controlled study , there could have been selection bias in patient assignment to groups . this study aimed to investigate the reperfusion time of patients with stemi in a definite time period only performed in a few county hospitals in henan province . our results may have been affected by cultural , geographical , medical resources , and economic conditions . overall , the primary percutaneous coronary intervention time of stemi patients was likely to be longer than that in developed countries , mainly due to pre - hospital delay , inter - hospital transfer time , consent delay , and medical cost delay . in summary , patients undergoing ppci for stemi with symptom onset to ihfmc times of 36 h via inter - hospital transfer had better 1-year survival than those with iht in the regional stemi program . our study also provides insights into the challenges in caring for stemi patients in rural areas . it is important to create more pci centers in smaller hospitals to improve the overall health of patients in the region .
backgroundthis study sought to compare the 30-day and 1-year survival of patients diagnosed with st - segment elevation myocardial infarction ( stemi ) , whose symptom onset to in - hospital first medical contact ( ihfmc ) was 36 h , who received either in - hospital thrombolysis ( iht ) in the nearest county hospital or direct transfer to a larger hospital in henan province , china for primary percutaneous coronary intervention ( ppci).material / methodspatients were allocated into 2 groups : one group received iht in the local county hospital , whereas the other group were transferred to the pci centers to receive ppci . 
 patient demographic data , baseline characteristics , and time between different stages of patient contact to the initiation of treatment for iht or ppci were recorded for analysis.resultsno significant difference was identified between the 2 groups with the baseline characteristics and demographic data . 
 the all - cause mortality was not significantly different between the iht and ppci group at 30 days ( 13.0% vs. 9.9% , p=0.386 ) . 
 however , a significant difference in mortality between the iht and ppci group was observed at 1 year ( 23.4% vs. 14.1% , p=0.035 ) . 
 inter - hospital transfer time for ppci tended to be the independent predictor for survival ( or : 4.4 ci 95% : 1.914.5 , p 0.001 ) . 
 overall , the patients undergoing ppci in inter - hospital transfer had a higher survival rates for 1 year compared with patients receiving iht.conclusionsdespite the delay associated with inter - hospital transfer for ppci , patients with stemi 36 h after symptom onset have improved survival with ppci over patients treated locally with iht .