Prof. Franz Josef Neumann,
Prof. Gilles Montalescot,
Presenter report : Montalescot Gilles (France)
For patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) in the randomized TRITON-TIMI 38 trial, prasugrel (60mg loading and 10mg maintenance dose) was superior to clopidogrel (300mg loading and 75mg maintenance dose) in reducing ischemic events, but with an increased risk of major bleeding. The objective of the present study was to compare prasugrel with clopidogrel in the prespecified STEMI subset of the TRITON-TIMI 38 trial.
Methods: The present analysis includes the 3,534 STEMI patients that were enrolled, either within 12 hours of the onset of symptoms for primary PCI, or > 12hours and < 14 days after the onset of symptoms for secondary PCI. Results: Baseline characteristics were well-matched between prasugrel and clopidogrel except for age (59.0 ± 11.2 prasugrel, 59.8 ± 11.6 clopidogrel, p=0.04) and tobacco use, which was more frequent with prasugrel. The median duration of therapy was 15 months and follow-up rate was 99.9%. PCI was performed in 97% of patients; use of bare metal stents was more frequent (59%) than use of drug-eluting stents (33%). Compared with clopidogrel, the composite endpoint of cardiovascular (CV) death, MI or stroke at 15 months was significantly reduced with prasugrel (12.4% vs 10.0% HR 0.79, 95% CI [0.65-0.97], P=0.02).
The key secondary endpoint of CV death, MI or urgent target vessel revascularization was also significantly reduced with prasugrel at 30 days (HR 0.75 [0.59-0.96], p=0.02) and at 15 months (HR 0.79; 0.64-0.97; P=0.025) with consistent reductions of the three elements of the composite end point. The double endpoint of CV death or MI was significantly reduced with prasugrel both at 30 days and 15 months. Stent thrombosis (ARC definite or probable) was also significantly reduced both at 30 days (2.4% clopidogrel vs. 1.2% prasugrel, p=0.008) and 15 months (2.8% clopidogrel vs. 1.6% prasugrel, p=0.02).
There was no significant difference between prasugrel and clopidogrel for non-CABG related TIMI major hemorrhage (2.4% vs. 2.1% respectively, p=NS), TIMI life-threatening bleeding (1.3% vs. 1.1%, p=NS), intracranial haemorrhage (0.2% vs. 0.3%, p=NS) and TIMI minor bleeding (2.8% vs. 2.7%, p=NS) over 15-months of follow-up. The reductions in the primary and secondary endpoints with prasugrel in the entire STEMI population were consistent in the two cohorts of patients undergoing primary and secondary PCI (p interaction = NS).
Conclusions: In patients with ST-elevation MI undergoing percutaneous coronary intervention, prasugrel was more effective than clopidogrel at preventing serious ischemic events without an apparent excess of bleeding.
Presenter report : Neumann Franz Josef (Germany 974Analysis of the TRITON TIMI 38 cohort with ST-elevation myocardial infarction (STEMI) reveals that the net clinical benefit of prasugrel versus clopidogrel is superior in patients with STEMI as compared with patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI). Slides Available
With respect to the composite of death, myocardial infarction, stroke or major non-CABG bleeding, the number needed to treat is 42 in STEMI as compared with 69 in UA/NSTEMI patients. This can be attributed to a similar efficacy in STEMI as compared with UA/NSTEMI, but superior safety. The number needed to treat to prevent 1 death, myocardial infarction or stroke is 42 in STEMI versus 47 in UA/NSTEMI, whereas the numbers needed to harm with respect to TIMI major non-CABG bleed are 333 in STEMI patients but 142 in UA/NSTEMI patients. This difference in bleeding complications between the two subsets of the TRITON study can be attributed to a higher incidence of bleeding with clopidogrel in the STEMI cohort as compared with the UA/NSTEMI cohort whereas the incidences of TIMI major non-CABG bleeds in the prasugrel arms of the STEMI and the UA/NSTEMI cohorts were virtually identical. The higher incidence of bleeding complications in the clopidogrel arm of the STEMI group may be attributed to a higher use of GPIIb/IIIa receptor blockers in the STEMI cohort as compared with the UA/NSTEMI cohort. There are a number of caveats and open questions. First of all, this is a secondary analysis of a subset of the TRITON TIMI 38 study, although prespecified, and there were some inhomogeneities between the study arms in the STEMI cohort including age, distribution of Kilipp classes and smoking habits. These inhomogeneities require adjustment by appropriate statistical methods. Furthermore, the interaction of the study outcome with the use GPIIb/IIIa blockers and with the timing of the study drug (before, during or after PCI), deserves further statistical analyses.
Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM for the TRITON (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel) – TIMI 38 Investigators.
Clinical Trial Update I
This congress report accompanies a presentation given at the ESC Congress 2008. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.
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