Which of the following about Prasugrel is incorrect?
A. It is a new antiplatelet agent just approved on July 10, 2009 by the Food and Drug Administration (FDA) for use in patients with unstable angina or myocardial infarction who undergo percutaneous coronary intervention (PCI).
B. The mechanism is inhibition of the platelet adenosine diphosphate (ADP) receptor.
C. Prasugrel is more effective than ticlopidine and clopidogrel at inhibiting the ADP receptor largely because it is more efficiently metabolized, so more active metabolite is delivered to the platelet.
D. In the TRITON–TIMI 38 trial, prasugrel showed a reduction in the risk of myocardial infarction and stent thrombosis, and there was also less major bleeding events.
Answer: D
Although TRITON–TIMI 38 demonstrated a reduction in the risk of myocardial infarction and stent thrombosis, there was an increase in major bleeding events, including a small but statistically significant excess of fatal bleeding events (approximately 3 such events per 1000 patients treated). As the risk of bleeding might be increased still further with real-life use, and the FDA has required that prasugrel’s labeling include a black-box warning about that risk.
References
1. Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res 2007;100:1261-1275. [Free Full Text]
Bhatt DL. Intensifying platelet inhibition — navigating between Scylla and Charybdis. N Engl J Med 2007;357:2078-2081. [Free Full Text]
2. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015. [Free Full Text]
3. Curfman GD, Morrissey S, Jarcho JA, Drazen JM. Drug-eluting coronary stents — promise and uncertainty. N Engl J Med 2007;356:1059-1060. [Free Full Text]
4. Bavry AA, Bhatt DL. Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis. Lancet 2008;371:2134-2143. [Erratum, Lancet 2008;372:536.] [CrossRef][Web of Science][Medline]
Also see NEJM Perspective here.