Comparison of In-hospital Outcomes Following Early or Delayed Angioplasty for Acute Myocardial Infarction

Rapid reperfusion with fibrinolytic drugs following acute myocardial infarction (AMI) is associated with increased myocardial salvage and improved survival.1,2 However, the efficacy of these agents begins to diminish when they are administered more than six hours after symptom onset and little benefit can be demonstrated after 12 hours.2–4 In contrast, studies of primary percutaneous transluminal coronary angioplasty (PTCA) for treatment of AMI have not appeared to demonstrate a reduction in efficacy as a function of time to treatment.5–7 However, these studies were not population-based and thus may not be representative of results achieved outside the setting of clinical trials or at highly experienced primary PTCA centers. We sought to compare the outcomes of patients treated in New York State with primary angioplasty within 6 hours of symptom onset to those treated between 6 and 23 hours after the onset of AMI. Other investigators have used the New York State Coronary Angioplasty Reporting System database for studies of angioplasty treatment of AMI, but time to treatment has not been evaluated.8 This dataset was used because it represents the experience across an entire state and included patients treated in rural and urban, teaching and nonteaching as well as not-for-profit and for-profit hospitals. Furthermore, the data are not dominated by one or several institutions with particular expertise in the treatment of patients with AMI. Finally, the patients are those encountered in actual practice rather than the lower risk patients frequently selected for enrollment in randomized trials. Methods We used data from the 1995 Coronary Angioplasty Reporting System of the New York State Department of Health (DOH). This registry was developed in 1990 to track and record important information on every patient undergoing PTCA in New York State. The responsible physician, or a designee, completes a questionnaire after each intervention, which is subsequently entered into a computer database and sent to the DOH. The questionnaire contains information on the hospital and cardiologist, patient demographics, procedural information, risk factors, discharge status, vessels diseased, lesion location and morphology, presence of bypass grafts, pre- and post-procedural stenosis and complications. The DOH is the coordinating center, and hospitals and their catheterization laboratories are responsible for the accurate documentation and transfer of data. The DOH conducts periodic site visits to check for the accuracy of data entry, and errors and discrepancies are brought to the attention of each laboratory for rectification. The 1995 New York State Coronary Angioplasty Registry includes > 22,000 patients undergoing elective and emergent PTCA in 32 hospitals. The time from onset of AMI symptoms to treatment is recorded as Statistical analysis. Categorical variables were compared by Chi-squared analysis. Continuous variables were compared using student’s t-tests. All probability values are 2-tailed. Characteristics of patients in the early and delayed groups that differed on univariate analysis with a p-value of Outcomes. Overall in-hospital mortality was 63/1,342 (4.7%) with no difference based on early or delayed PTCA (5.2% versus 3.4%, respectively; p = NS). Post-procedure reinfarction (0.2% versus 0.8%, respectively; p = NS) and emergency bypass surgery rates (2.9% versus 2.3%, respectively; p = NS) were also similar regardless of time to PTCA. Major adverse cardiac events (MACE) including in-hospital death, reinfarction and emergency bypass surgery did not differ significantly between the early and delayed PTCA groups (7.7% versus 5.5%, respectively; p = NS). Multivariate predictors. In multivariate models, only unstable hemodynamic status, cardiogenic shock and malignant ventricular arrhythmias were independent predictors of in-hospital mortality (Table 3) or the composite of MACE (Table 4). Delayed PTCA for AMI was not an independent predictor of either in-hospital mortality or MACE. Discussion Our analysis of patients undergoing PTCA for AMI in New York State demonstrates that treatment between 6 and 23 hours following symptom onset does not result in greater in-hospital mortality or MACE compared to patients treated within 6 hours. There were significant differences between patients treated early and late. Patients treated early tended to be more hemodynamically and electrically unstable, whereas patients undergoing delayed PTCA were older and more often female. However, after multivariable regression to adjust for differences between groups, we were still unable to detect an increased risk among patients treated between 6 and 23 hours. These results are concordant with those of the Second National Registry of Myocardial Infarction (NRMI-2), the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO) IIb trial and the Stent Primary Angioplasty in Myocardial Infarction (Stent PAMI) trial that demonstrated no relationship between total time to reperfusion with primary PTCA and early mortality.4–6 The results of these studies should stimulate reevaluation of the mechanism of benefit of reperfusion in the setting of AMI. The traditional paradigm suggests that the benefit of early reperfusion is related to greater myocardial salvage, which results in improved left ventricular function and enhanced survival.9,10 However, the time period for myocardial salvage may be relatively short. The initial description of the wavefront of myocardial necrosis in the canine model of myocardial infarction found that little myocardium was viable when reperfusion was performed more than 2 hours after coronary occlusion.11 This finding is supported by the Moses Cone Hospital Registry, which found that only those patients who underwent primary PTCA within 2 hours of symptom onset had a reduction in mortality. After 2 hours, mortality was constant with increasing time to reperfusion.12 The lack of an increase in mortality with later reperfusion times supports the concept of a time-independent benefit of an open artery unrelated to myocardial salvage. Potential short-term benefits of an artery opened beyond the window for myocardial salvage include limitation of ventricular enlargement and improved electrical stability.9,10 The relative unimportance of time to reperfusion in primary angioplasty studies is in distinct contrast to studies of fibrinolytic therapy for AMI, where numerous studies have demonstrated a strong relationship between mortality benefit and time to treatment up to 12 hours.2,3 There are several potential explanations for the differences in effect on outcome of time to treatment for PTCA and fibrinolytic therapy. First, Thrombolysis in Myocardial Infarction (TIMI) 3 flow is achieved less often with increasing time to treatment with fibrinolytic drugs,13,14 whereas TIMI 3 flow is achieved in over 90% of patients undergoing primary PTCA regardless of time to treatment.12 Second, the frequency of cardiac rupture increases with increasing time to treatment with fibrinolytic drugs,15 while cardiac rupture is uncommon at any time point following primary PTCA.16 Third, the rate of intracranial hemorrhage increases with increasing time to treatment with fibrinolytic drugs,17 but intracranial hemorrhage is exceedingly uncommon at all time points with primary PTCA.18 In aggregate, the studies demonstrating no diminution of efficacy of primary PTCA have important implications for the care of patients who initially arrive in hospitals without the facilities for primary PTCA. These patients can be considered for transfer to a hospital with primary PTCA capability without concern that the time required for transfer will have a negative effect on outcomes. In fact, data exist suggesting that outcomes are superior in patients transferred for primary PTCA compared to those who receive thrombolytic therapy in local hospitals.19,20 Study limitations. There are several limitations to this study that must be borne in mind. First, the data are from 1995 when stent use for treatment of AMI was relatively uncommon. Second, due to its nonrandomized, retrospective nature, there may remain significant unrecognized differences between groups even after correction for the observed differences. However, unlike randomized trials, this study included high-risk patients typically excluded from clinical trials including those with advanced age and cardiogenic shock. Third, only in-hospital outcomes are available. It is possible that mortality rates on extended follow-up may differ between groups. Fourth, the exact time to treatment is not known. Thus, there may be differences in outcomes within the groups if the time to treatment could be further subdivided. Finally, this database contains no data on door to balloon time, which has been found to correlate with increased mortality even in settings where there was no correlation between total time to treatment and outcome. Presumably, door to balloon time reflects the efficiency and experience of a healthcare system in dealing with the AMI patient. Recent data suggest that both physician experience and hospital experience exert important effects on in-hospital survival among patients treated with primary PTCA for AMI.8 Conclusion. Delayed reperfusion does not influence in-hospital clinical outcomes following PTCA for AMI.

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