What are the clinical trials on dual antiplatelet therapy (DAPT)?

From the Guidelines

Dual antiplatelet therapy (DAPT) is recommended for at least 12 months in patients with coronary artery disease, including those with acute coronary syndrome (ACS) or after percutaneous coronary intervention (PCI) with stent placement, as it significantly reduces the risk of stent thrombosis and recurrent cardiovascular events 1. The choice of P2Y12 inhibitor, such as clopidogrel, ticagrelor, or prasugrel, should be based on individual patient characteristics and bleeding risk.

• For patients with ACS undergoing PCI, the recommendation is to use ticagrelor or prasugrel in preference to clopidogrel for maintenance therapy, if no contraindications exist 1.
• The duration of DAPT may vary based on bleeding risk and stent type, with drug-eluting stents generally requiring 6-12 months of DAPT, while bare metal stents may require only 1 month.
• Patients at high bleeding risk might receive shorter courses (3-6 months) of DAPT, while those at high ischemic risk might benefit from extended therapy beyond 12 months. Key considerations in determining the duration of DAPT include:
• The type of stent used (drug-eluting or bare metal)
• The patient's bleeding risk
• The patient's ischemic risk
• The presence of any contraindications to specific P2Y12 inhibitors Regular monitoring for bleeding complications is essential during DAPT, and therapy should be temporarily interrupted 5-7 days before major surgery when possible. The decision to extend DAPT beyond 12 months should be individualized, taking into account the patient's risk of ischemic events and bleeding complications, as well as their personal preferences and values 1.

From the FDA Drug Label

The clinical evidence for the effectiveness of prasugrel is derived from the TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel) study, a 13,608 patient, multicenter, international, randomized, double-blind, parallel-group study comparing prasugrel to a regimen of clopidogrel, each added to aspirin and other standard therapy, in patients with ACS (UA, NSTEMI, or STEMI) who were to be managed with PCI.

The trials on dual antiplatelets, specifically prasugrel and clopidogrel, were conducted in the TRITON-TIMI 38 study.

• Key findings:
  • Prasugrel significantly reduced total endpoint events compared to clopidogrel.
  • The reduction of total endpoint events was driven primarily by a decrease in nonfatal MIs.
  • Prasugrel produced higher rates of clinically significant bleeding than clopidogrel.
• Study design:
  • 13,608 patients with ACS (UA, NSTEMI, or STEMI) were randomized to receive prasugrel or clopidogrel, each added to aspirin and other standard therapy.
  • Patients underwent PCI, and the study drug was administered after the first coronary guidewire was placed in approximately 75% of patients.
  • The primary outcome measure was the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in the UA/NSTEMI population. 2

From the Research

Dual Antiplatelet Therapy Trials

• The American Heart Association/American College of Cardiology guidelines recommend dual antiplatelet therapy (DAPT) for 1 year in patients presenting with an acute coronary syndrome, with a Class IIb recommendation for continuation 3.
• A meta-analytic approach found no significant difference in cardiovascular mortality, myocardial infarction, or major bleeding between short-term and 12-month/extended DAPT 3.
• However, compared with extended DAPT, 12-month DAPT showed significantly higher risk of myocardial infarction, but reduced risk of major bleeding 3.
• An individualized approach is needed, taking into account the competing risks of bleeding and ischemic events 3, 4.

Duration of Dual Antiplatelet Therapy

• Short-term DAPT (≤3 months or 6 months) did not increase ischemic outcomes compared to long-term DAPT (12 months and >12 months) 5.
• For bleeding outcomes, ≤3 months DAPT was associated with significant reduction in bleeding compared to 6 months, 12 months or >12 months DAPT 5.
• Guidelines might need to consider short-term DAPT even in patients presenting with ACS, especially in this era of newer generation drug eluting stents 5.
• Current guidelines recommend the use of DAPT for 1 year in all patients with ACS, with ticagrelor 60 mg recommended for up to 3 years in high-risk patients 6.

Comparison of P2Y12 Inhibitors

• Ticagrelor was associated with a significantly lower risk of major adverse cardiovascular events (MACE) and hospitalization compared with clopidogrel after PCI for ACS 7.
• No difference was observed in the risk of major bleeding between ticagrelor and clopidogrel 7.
• A statistically nonsignificant trend toward reduced risk of all-cause mortality was noted with ticagrelor compared to clopidogrel 7.
• The newer antiplatelets ticagrelor and prasugrel have demonstrated superiority over clopidogrel 4, 6.