Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction

Abstract

Background: The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations.

Objectives: This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI.

Methods: The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding.

Results: Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21).

Conclusions: Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938).

Keywords: acute coronary syndromes; antiplatelet therapy; myocardial infarction; percutaneous coronary intervention; randomized clinical trial.

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Enrollment, randomization and follow-up of patients in the DAPT Study stratified by acute myocardial infarction status at presentation

Patients were enrolled within 72 hours after placement of either a bare metal or drug-eluting stent, and received open-label treatment with aspirin and thienopyridine. Eligible subjects were then randomized to thienopyridine or placebo, while continuing aspirin, and followed for an additional 18 months (months 12–30).

Figure 2. Cumulative incidence of stent thrombosis according to randomization arm for patients with (Panel A) and without (Panel B) acute myocardial infarction

Randomization occurred 12 months after initial presentation. Endpoint includes definite or probable stent thrombosis as assessed according to the criteria of the Academic Research Consortium. The effect of continued thienopyridine on stent thrombosis was similar for patients with vs. without myocardial infarction at presentation (interaction p=0.69).

Figure 3. Cumulative incidence of major adverse cardiovascular and cerebrovascular events (MACCE) according to randomization arm for patients with (Panel A) and without (Panel B) acute myocardial infarction

MACCE was defined as the composite of death, myocardial infarction or stroke. Randomization occurred 12 months after initial presentation. The effect of continued thienopyridine on MACCE was greater for patients with MI compared with patients without myocardial infarction at presentation (interaction p=0.03).

Figure 4. Cumulative incidence of myocardial infarction according to randomization arm for patients with (Panel A) and without (Panel B) acute myocardial infarction

Randomization occurred 12 months after initial presentation. The effect of continued thienopyridine on myocardial infarction was similar for patients with vs. without myocardial infarction at presentation (interaction p=0.15).