What is the role of DAPT in the treatment of coronary artery atherosclerosis?

Updated: Apr 09, 2021
  • Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Yasmine S Ali, MD, MSCI, FACC, FACP  more...
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Answer

Antiplatelet agents help reduce the number of acute coronary events, as demonstrated from the following studies:

  • Antiplatelet Trialists' Collaboration [74]

  • Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial [75]

  • Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial [76]

  • Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes (TRITON TIMI-38) [77]

The CAPRIE trial studied the efficacy of clopidogrel (an inhibitor of the P2Y12 adenosine-diphosphate receptor), compared with that of aspirin, on long-term events. [75] Recurrent cardiovascular events were modestly reduced in patients treated with clopidogrel, in comparison with aspirin.

Extending this, the CURE trial found that regardless of the initial treatment strategy (medical therapy, PCI, or CABG), treatment with the combination of aspirin and clopidogrel was superior to aspirin alone in reducing recurrent events for up to 12 months after hospitalization with ACS. However, in the CHARISMA trial, prolonged dual antiplatelet therapy with aspirin and clopidogrel did not significantly reduce recurrent events in patients with stable cardiovascular disease or in asymptomatic patients at high risk for cardiovascular events.

In the TRITON TIMI-38 trial, prasugrel, a more potent thienopyridine P2Y12 inhibitor, proved more effective than clopidogrel in reducing ischemic events, including stent thrombosis, among patients with ACS who were scheduled for percutaneous coronary intervention. However, the risk of major bleeding, including fatal bleeding, was higher with prasugrel (2.4% versus 1.8% with clopidogrel), although overall mortality did not differ significantly between treatment groups.

Low-dose prasugrel may also be effective in very elderly patients. In a pharmacodynamic and pharmacokinetic study involving 155 patients with stable CAD, investigators found that a 5-mg dose of prasugrel provided adequate platelet inhibition in very elderly patients. [78, 79] The study subjects, who were either aged 45-65 years (mean, 56 y) or older than 75 years (mean, 79 y), were treated for 12 days during each of 3 crossover treatment periods with 1 of 3 regimens: clopidogrel 75 mg, prasugrel 5 mg, or prasugrel 10 mg.

Median maximal platelet aggregation (MPA) response to prasugrel 5 mg in very elderly patients (58%) was noninferior to the 75th percentile of MPA response to prasugrel 10 mg in nonelderly patients (52%). [79] Antiplatelet effect was significantly lower and high on-treatment platelet reactivity rates significantly higher with prasugrel 5 mg in very elderly patients than with prasugrel 10 mg in nonelderly patients. Prasugrel 5 mg had significantly greater antiplatelet effect than clopidogrel 75 mg in very elderly patients, as did prasugrel 10 mg in nonelderly patients. [79]

The incidence of bleeding-related adverse events in older patients was similar to that in younger patients. [79] Bleeding rates were similar with prasugrel 5 mg and clopidogrel 75 mg but were significantly higher with prasugrel 10 mg.


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