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 treatmentdelay modulates this treatment effect is unclear. Methods and results Twenty-five randomized trials (n=7743) testingthe efficacy of PPCI vs. FL were identified in journal articlesand 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 relationshipamong treatment, treatment delay, and 30-day mortality. Treatmentdelay was divided into ‘presentation delay’ [symptomonset to randomization; FL: median 143 (IQR: 91–225) min;PPCI: 140 (91–220) min] and hospital-specific ‘PCI-relateddelay’ [median time from randomization to PPCI minus mediantime to FL per hospital; median 55 (IQR: 37–74) min].PPCI was associated with a significant 37% reduction in 30-daymortality [adjusted OR, 0.63; 95% CI (0.42–0.84)].Although, there was no heterogeneity in the treatment effectby presentation delay (pBreslow-Day=0.88), the absolute mortalityreduction by PPCI widened over time (1.3% 0–1 h to4.2% >6 h after symptom onset). When the PCI-relateddelay was <35 min, the relative (67 vs. 28% pBreslow-Day=0.004)and absolute (5.4 vs. 2.0%) mortality reduction was significantlyhigher than those with longer delays. Conclusion PPCI was associated with significantly lower 30-daymortality relative to FL, regardless of treatment delay. Althoughlogistic and economic constraints challenge the feasibilityof ‘PPCI-for-all’, the benefit of timely treatmentunderscores the importance of a comprehensive, unified approachto delivery of cardiac care in all AMI patients.