Dual antiplatelet therapy (aspirin plus clopidogrel) did not appear to be more effective than aspirin alone in reducing the rate of cardiac death or myocardial infarction (MI), according to pooled data from the Correlation of Clopidogrel Therapy Discontinuation in Real-World Patients Treated with Drug-Eluting Stent Implantation and Late Coronary Artery Thrombotic Events (REAL-LATE; NCT00484926) and Evaluation of the Long-Term Safety After Zotarolimus-Eluting Stent, Sirolimous-Eluting Stent, or Paclitaxel-Eluting Stent Implantation for Coronary Lesions Late Coronary Arterial Events (ZEST-LATE; NCT00590174) Trials. The two trials were merged due to their design similarity and slow enrollment, and merged results were presented by Seung-Jung Park, MD, PhD, Asan Medical Center, Seoul, Korea.

Current guidelines recommend the use of clopidogrel 75 mg daily for at least 12 months post-drug-eluting stent (DES) implantation, provided that the patient is not at high risk of bleeding. While early discontinuation of dual antiplatelet therapy is associated with a higher risk of late stent thrombosis in patients with DES, there is no consistent data regarding the appropriate treatment duration and the long-term outcomes that are associated with dual antiplatelet therapy in these patients. The merged data analysis by Dr. Park and colleagues sought to compare antiplatelet strategies in patients on dual antiplatelet therapy who were free of major adverse cardiovascular events (MACEs) and major bleeding for at least 12 months post-DES implantation.

Patients in these two open-label trials were randomized to receive either clopidogrel 75 mg daily plus low-dose aspirin (100 to 200 mg daily; n=1357) or low-dose aspirin alone (n=1344). Patients were well matched at baseline. However, the REAL-LATE participants included a broader population that did not limit clinical or lesion characteristics. Exclusion criteria across the studies included contraindications to antiplatelet drugs, concomitant vascular disease or other indications that required the long-term use of clopidogrel, noncardiac comorbidities that limited life expectancy to <1 year, and participation in another drug or coronary device study. Follow-up evaluations were performed every 6 months, and the median duration of follow-up was 19.2 months. The primary endpoint was the first occurrence of MI or death from cardiac causes postrandomization. The secondary endpoints included major bleeding, as defined by Thrombolysis in Myocardial infarction (MI) criteria; a composite of death or MI; a composite of death, MI, or stroke; a composite of cardiac death, MI, or stroke; or individual components, including death, MI, stroke of any cause, definite stent thrombosis, or repeat revascularization.

The risk of cardiac death or MI was similar for both groups (1.8% for dual therapy vs 1.2% for monotherapy; p=0.17). The composite risk of MI, stroke, or death from any cause was slightly higher in the dual therapy group (HR, 1.73; 95% CI, 0.99 to 3.00; p=0.051), as was the composite risk of MI, stroke, or death from cardiac causes (HR, 1.84; 95% CI, 0.99 to 3.45; p=0.06). However, neither of these increases reached statistical significance. The risks that were associated with the individual components of the secondary endpoint were similar in both groups. Overall, the use of dual antiplatelet therapy beyond 12 months post-DES implantation did not significantly reduce the risk of MI or death from cardiac causes compared with aspirin monotherapy.

Dr. Park concluded that this study had insufficient statistical power to determine the safety of clopidogrel discontinuation after 12 months. Therefore, larger clinical trials with a longer-term follow-up are needed to evaluate the risk of clopidogrel discontinuation.