ArticlesPrasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial
Introduction
Major innovations in catheter-based management of ST-segment elevation myocardial infarction (STEMI) include use of bare metal and drug-eluting stents and platelet glycoprotein IIb/IIIa inhibitors. Use of drug-eluting stents has significantly lowered restenosis but has had little effect on ischaemic events such as death, reinfarction, or stent thrombosis.1, 2, 3 Conversely, glycoprotein IIb/IIIa inhibitors have had no effect on restenosis but have been associated with a reduction in major ischaemic events associated with percutaneous coronary intervention (PCI) in patients with STEMI.4
As use of stents has grown, thienopyridines—especially clopidogrel—have become increasingly important for treatment of STEMI.5, 6, 7, 8, 9, 10 However, up to now, no randomised controlled trials have been undertaken to compare clopidogrel (or the first-generation thienopyridine, ticlopidine) with placebo in patients undergoing PCI for STEMI. The effectiveness of clopidogrel in this setting has been presumed on the basis of results of studies of scheduled PCI.11, 12, 13
Prasugrel is a novel third-generation thienopyridine and a more potent blocker of the platelet P2Y12 receptor than clopidogrel, producing consistent platelet inhibition.14 The TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 was designed to compare clopidogrel with prasugrel. In a previous report, prasugrel was superior to clopidogrel in reduction of ischaemic events in patients undergoing PCI for the entire spectrum of acute coronary syndrome, albeit with increased bleeding.15 We report here results for the STEMI population, which represents the first large experience for prasugrel in mechanical reperfusion of STEMI.
Section snippets
Participants
TRITON-TIMI 38 was a randomised, double-blind, double-dummy, parallel group trial to compare prasugrel with clopidogrel in 707 sites in 30 countries. The study design and main results have been reported elsewhere.15, 16
The present prespecified report focuses on patients with STEMI. We divided participants into two strata: (1) those enrolled within 12 h of onset of symptoms (primary PCI); and (2) those enrolled between 12 h and 14 days after symptom onset (secondary PCI). Patients undergoing
Results
A total of 3534 STEMI patients were enrolled and underwent random allocation (figure 1). Baseline characteristics were well matched between prasugrel and clopidogrel groups (table 1), except that age was slightly higher in individuals assigned clopidogrel than in those allocated prasugrel. Median duration of treatment for STEMI patients was 15·2 months (IQR 14·6–15·5), which was longer than for participants with unstable angina or non-STEMI (12·5 months [8·4–15·2]) because enrolment in the
Discussion
This analysis of STEMI patients in TRITON-TIMI 38 shows that, for the specific regimens that were administered, prasugrel—when compared with clopidogrel—was associated with a significant risk reduction in the primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke for the trial duration. A significant reduction in the key secondary composite endpoint of cardiovascular death, non-fatal myocardial infarction, or urgent target vessel
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