Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients

Aims Although outcomes after acute myocardial infarction (AMI) seemed to be superior with primary percutaneous coronary intervention (PPCI) relative to fibrinolysis (FL), the extent to which treatment delay modulates this treatment effect is unclear. Methods and results Twenty-five randomized trials (n=7743) testing the efficacy of PPCI vs. FL were identified in journal articles and abstract listings published between 1990 and 2002. Of these, individual patient data from 22 trials (n=6763) were pooled, and multi-level logistic regression assessed the relationship among treatment, treatment delay, and 30-day mortality. Treatment delay was divided into 'presentation delay' [symptom onset to randomization; FL: median 143 (IQR: 91-225) min; PPCI: 140 (91-220) min] and hospital-specific 'PCI-related delay' [median time from randomization to PPCI minus median time to FL per hospital; median 55 (IQR: 37-74) min]. PPCI was associated with a significant 37% reduction in 30-day mortality [adjusted OR, 0.63; 95% CI (0.42-0.84)]. Although, there was no heterogeneity in the treatment effect by presentation delay (pBreslow-Day=0.88), the absolute mortality reduction by PPCI widened over time (1.3% 0-1 h to 4.2% > 6 h after symptom onset). When the PCI-related delay was < 35 min, the relative (67 vs. 28% pBreslow-Day=0.004) and absolute (5.4 vs. 2.0%) mortality reduction was significantly higher than those with longer delays. Conclusion PPCI was associated with significantly lower 30-day mortality relative to FL, regardless of treatment delay. Although logistic and economic constraints challenge the feasibility of 'PPCI-for-all', the benefit of timely treatment underscores the importance of a comprehensive, unified approach to delivery of cardiac care in all AMI patients.