Prasugrel vs. Clopidogrel After Myocardial Infarction [Новость добавлена - 11.03.2009]

Prasugrel was more effective for preventing ischemic events in patients who underwent percutaneous coronary interventions.

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Summary and Comment

Prasugrel is an analogue of clopidogrel that has more-consistent
platelet-inhibitory activity and faster onset of action. In a previous
trial, prasugrel was more effective than clopidogrel for preventing adverse
coronary events (JW Oncol Hematol Dec 4 2007). However, use of prasugrel
was associated with higher bleeding rates; therefore, researchers have
questioned whether the agent benefits patients with ST-segment-elevation
myocardial infarction (STEMI) who undergo percutaneous coronary
interventions (PCIs).

To address these concerns, investigators performed an industry-supported,
multinational, randomized trial involving 3534 patients with STEMI who were
assigned to receive either clopidogrel (300 mg loading dose and then 75 mg
daily) or prasugrel (60 mg loading dose and then 10 mg daily) within 1 hour
of PCI. All patients were given aspirin within 24 hours of PCI. In a second
randomization, the same patients were divided into two groups: 2438 who
were enrolled within 12 hours of symptom onset (primary PCI group) and 1094
who were enrolled between 12 hours and 14 days of symptom onset (secondary
PCI group); 2 did not participate. Individuals in the secondary PCI group
were more likely to have undergone previous revascularization (P=0.02) and
multivessel PCI (P=0.0001). Overall, bare-metal stents were used more often
than drug-eluting stents (59% vs. 33%).

At 15-month follow-up, the primary endpoint of cardiovascular death,
nonfatal MI, and nonfatal stroke occurred significantly more often in those
who received clopidogrel than in those who received prasugrel (12.4% vs.
10.0%; P=0.022); the difference was not significant for patients in the
primary PCI group (11.6% and 10.2%; P=0.266) but was significant for
patients in the secondary PCI group (14.1% vs. 9.6%; P=0.015). Stent
thrombosis was more common in patients who received clopidogrel than in
those who received prasugrel (2.8% vs. 1.6%; P=0.023); this difference in
rate of stent thrombosis between the two drugs was significant only among
patients in the primary PCI group (2.7% vs. 1.5%; P=0.048). Endpoints were
generally reached within 30 days of randomization, after which the
cumulative-incidence curves for clopidogrel and prasugrel remained
parallel, suggesting that prasugrel did not confer a long-term benefit
compared with clopidogrel. Among the 4% of patients who underwent
coronary-artery bypass grafting (CABG), major bleeding was more common in
those who received prasugrel than in those who received clopidogrel (18.8%
vs. 2.7%; P=0.003); bleeding that was unrelated to CABG was similar between
patients who received prasugrel and those who received clopidogrel (2.4%
and 2.1%; P=0.65).

Comment: These results suggest that prasugrel, a powerful inhibitor of
platelet function, can play a major role in managing patients with ischemic
disease. However, because prasugrel poses a risk for bleeding, patient
selection for this drug will be important. Patients with acute coronary
syndromes and previous or failed PCI seem to achieve the most benefit from
prasugrel. In addition, those with CYP2C19 mutations that impair the
conversion of clopidogrel to its active metabolite should be considered for
prasugrel treatment. In any case, the drug should never be initiated (or
should be promptly discontinued) in patients who require major surgical
procedures.

-- David Green, MD, PhD

Published in Journal Watch Oncology and Hematology March 10, 2009
Citation(s):

Montalescot G et al. Prasugrel compared with clopidogrel in patients
undergoing percutaneous coronary intervention for ST-elevation myocardial
infraction (TRITON-TIMI 38): Double-blind, randomised controlled trial.
Lancet 2009 Feb 28; 373:723. (Free)