What is the role of prasugrel in the treatment of acute coronary syndrome (ACS)?

Updated: Sep 30, 2020
  • Author: David L Coven, MD, PhD; Chief Editor: Eric H Yang, MD  more...
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Like clopidogrel, prasugrel is a thienopyridine ADP receptor inhibitor that inhibits platelet aggregation. It has been approved in the United States and has been shown to reduce new and recurrent myocardial infarctions. [69] The loading dose is 60 mg PO once and maintenance is 10 mg PO qd (given with aspirin 75-325 mg/d). Prasugrel is indicated for the reduction of thrombotic cardiovascular events (including stent thrombosis) with ACS that is managed with PCI.

However, a 2014 report by Montalescot et al indicates that if angiography is to be performed in a patient with NSTEMI within 48 hours of admission, treatment with the P2Y12 antagonist prasugrel should be postponed until a decision about revascularization has been reached owing to an increased bleeding risk without ischemia benefit from pre-PCI prasugrel therapy. [70, 71] The randomized, double-blind study included 2770 NSTEMI patients who underwent percutaneous coronary intervention (PCI), with 1394 patients receiving pretreatment with prasugrel and 1376 individuals receiving placebo. All patients received prasugrel at the time of PCI.

The investigators found that the same percentage of patients (13.1%) in the pretreatment and placebo groups reached primary endpoint (defined as time to first occurrence of glycoprotein IIb/IIIa bailout, stroke, myocardial infarction [MI], urgent revascularization, or cardiovascular death, through 7 days after randomization). [70, 71] No reductions in ischemic events, including total mortality, were found in the patients who received prasugrel pretreatment. Moreover, pretreatment with prasugrel was associated with a six-fold increase in life-threatening bleeding unrelated to coronary artery bypass grafting (CABG), as well as a three-fold increase in all major bleeding associated with non-CABG thrombolysis in myocardial infarction (TIMI). An approximately three-fold increase in TIMI minor bleeding events was also seen. [70, 71]

Earlier studies also found that significant, sometimes fatal, bleeding occurred more frequently with prasugrel than with clopidogrel, although the overall mortality rate did not differ significantly between a treatment group receiving prasugrel and another receiving clopidogrel. [69, 72]

In a separate, earlier study of patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel, compared with clopidogrel, did not significantly reduce the frequency of the primary end point of death from cardiovascular causes, myocardial infarction, or stroke. Similar bleeding risks were observed. [73]

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