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)

Udell JA, Braunwald E, Antman EM, et al.
JACC Cardiovasc Interv. 2014 Jun;7(6):604-12

Background

The preferred therapy for patients presenting with ST-segment elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PCI). If mechanical reperfusion is not available, fibrinolysis is a routinely used alternative method. When patients present later than the recommended time window for primary PCI or fibrinolytic therapy (<12 h from symptom onset), but when they remain symptomatic or present with other high-risk features, secondary PCI may be needed [1,2].
The TRITON-TIMI 38 trial demonstrated the benefit of dual antiplatelet therapy with prasugrel, as compared with clopidogrel, in moderate- to high-risk acute coronary syndrome (ACS) patients undergoing planned PCI [3]. STEMI-patients appeared to benefit in particular [4].
The benefit of more rapid, consistent, and effective P2Y12 receptor blockade among STEMI patients reperfused via primary, as compared with secondary PCI, is unclear. This prespecified subgroup analysis of TRITON-TIMI 38 therefore aimed to assess the efficacy and safety of prasugrel as compared with clopidogrel according to the timing of PCI. Among 3425 STEMI patients who underwent PCI, 2340 (68%) received primary PCI and 1085 (32%) received secondary PCI.

Main results

• Among patients managed with primary PCI, median time from symptom onset to randomisation for STEMI was 3.7 hours (IQR: 2.3-6.6), while this was 47.3 hours (IQR: 25.7-86.2) among those receiving secondary PCI (P<0.0001).
• A tendency toward a difference in treatment effect of prasugrel for 30 days, as compared with clopidogrel, was seen between primary and secondary PCI-managed patients for the primary endpoint (primary: HR: 0.81, 95%CI: 0.60-1.09 vs. secondary: HR: 0.51, 95%CI: 0.34-0.76, P(interaction): 0.06) and CV death, nonfatal MI or urgent target vessel revascularisation (primary: HR: 0.91, 95%CI: 0.67-1.23 vs. secondary: HR: 0.53, 95%CI: 0.35-0.79, P(interaction): 0.03). The difference was mostly driven by a reduction in risk of MI seen among secondary PCI-managed patients.
• At 15-months, the reduction of primary endpoint events minus periprocedural MI was consistent among primary and secondary PCI-managed patients (primary: HR: 0.89, 95%CI: 0.69-1.13 vs. secondary: HR: 0.65, 95%CI: 0.46-0.93, P(interaction)=0.15). Consistent effects of prasugrel irrespective of PCI timing were also seen for other major efficacy endpoints, except for MI.
• No significant difference was seen between treatment groups with respect to non-CABG-related TIMI major bleeding events. Risk of TIMI major bleeding events was however lower with prasugrel vs. clopidogrel with secondary PCI (HR: 0.39, 95%CI: 0.14-1.11) as compared with primary PCI (HR: 1.52, 95%CI: 0.87-2.65, P(interaction)=0.02).
• A significant interaction between PCI timing and treatment was only seen for periprocedural MI events, with a higher risk at primary PCI than secondary PCI. Non-procedural MI was consistently reduced with prasugrel vs. clopidogrel in both primary and secondary PCI-managed patients.

Conclusion

This secondary analysis of TRITON-TIMI 38 shows that the benefit of prasugrel over clopidogrel is consistent among patients managed with primary and secondary PCI, at 15 months. When looking at 30 days, prasugrel tended to confer less benefit with primary PCI, but not when periprocedural MIs were excluded from analysis. Procedural MIs were less common among primary PCI patients, possibly because they are less clearly distinguishable from the index MI. Secondary PCI patients may represent a highly selective group who benefit on the long run from more potent antithrombotic therapy.
Thus, the efficacy of prasugrel as compared with clopidogrel is consistent, irrespective of timing of PCI, specifically in the prevention of nonprocedural events.

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References

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