Prasugrel Versus Clopidogrel in Patients With ST-Segment Elevation Myocardial Infarction According to Timing of Percutaneous Coronary Intervention: A TRITON–TIMI 38 Subgroup Analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38)
What is the efficacy of prasugrel versus clopidogrel in ST-segment elevation myocardial infarction (STEMI) by the timing of percutaneous coronary intervention (PCI)?
STEMI patients in the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38) study were randomized to prasugrel or clopidogrel on presentation if primary PCI was intended, or later during secondary PCI. Primary PCI was defined as within 12 hours of symptom onset. The primary endpoint was cardiovascular death, MI, or stroke. Because periprocedural MI is difficult to assess in the setting of STEMI, the investigators performed analyses excluding these events.
Reductions in the primary endpoint with prasugrel versus clopidogrel (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.65-0.97; p = 0.022) were consistent between primary and secondary PCI patients at 15 months (HR, 0.89; 95% CI, 0.69-1.13 vs. HR, 0.65; 95% CI, 0.46-0.93; p interaction = 0.15). However, a tendency toward a difference in treatment effect at 30 days (HR, 0.68; 95% CI, 0.54-0.87; p = 0.002) was observed between primary and secondary PCI patients (HR, 0.81; 95% CI, 0.60-1.09 vs. HR, 0.51; 95% CI, 0.34-0.76; p interaction = 0.06). When periprocedural MI was excluded, the efficacy of prasugrel remained consistent among primary and secondary PCI patients at 30 days (HR, 0.53; 95% CI, 0.34-0.81 vs. HR, 0.44; 95% CI, 0.22-0.88; p interaction = 0.68) and 15 months (HR, 0.76; 95% CI, 0.56-1.03 vs. HR, 0.75; 95% CI, 0.46-1.21; p interaction = 0.96).
The authors concluded that the efficacy of prasugrel versus clopidogrel was consistent irrespective of the timing of PCI, particularly in preventing nonprocedural events.
This secondary analysis of the TRITON–TIMI 38 population reports that patients with STEMI who were managed with PCI late after presentation appeared to be a highly selected group who derived long-term efficacy from more potent antithrombotic therapy with a more favorable risk balance for spontaneous bleeding. Primary and secondary PCI–managed STEMI patients demonstrated consistent efficacy results when treated with prasugrel compared with clopidogrel, except regarding the development of procedural MI. When nonprocedural MIs were considered apart from procedural events, the benefit of prasugrel was consistent, irrespective of the timing of PCI.
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