Clopidogrel associated with better cardiovascular outcomes compared with aspirin in patients with and without diabetes – A post hoc analysis of the HOST-EXAM trial

1. In this secondary analysis of the HOST-EXAM randomized clinical trial, clopidogrel monotherapy was associated with lower rates of the composite end point of all-cause death, myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding in patients with and without diabetes.

2. The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for thrombotic composite endpoint and any major bleeding with Bleeding Academic Research Consortium 2,3, or 5.

Evidence Rating Level:1 (Excellent)

Study Rundown: Aspirin is the current standard for long-term maintenance antiplatelet monotherapy in patients who have received percutaneous coronary intervention. Selecting the optimal antiplatelet agent in patients with diabetes is especially important due to the heightened risk of ischemic events. The Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Extended Antiplatelet Monotherapy (HOST-EXAM) trial found that clopidogrel was associated with better cardiovascular outcomes than aspirin in patients who had successfully completed due duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. The objective of this secondary analysis of the HOST-EXAM trial was to investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. Patients were randomized 1:1 to receive either clopidogrel or aspirin monotherapy. The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding at 24-month follow-up. A total of 1860 patients had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 patients completed follow-up. The rate of the primary composite endpoint was found to be significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes and without diabetes. Diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for thrombotic composite endpoint and any bleeding with Bleeding Academic Research Consortium 2,3 or 5. A limitation of this study was that since the randomization was not stratified according to diabetes status, the study was not equipped to compare outcomes between both monotherapies in patients with or without diabetes. Strengths, however, were the choice of study design with a rigorous methodology and large sample size. Overall, this study demonstrated that clopidogrel monotherapy was associated with a lower rate of the primary composite endpoint compared with aspirin as a long-term maintenance therapy after DAPT for percutaneous coronary intervention in patients with and without diabetes.

Click to read the study in JAMA Cardiology

Relevant Reading: Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis

In-Depth [randomized controlled trial]: This study investigated cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. The HOST-EXAM prospective, randomized, multicenter trial was performed at 37 centers in Korea. Patients who received DAPT without clinical events for 6-18 months after coronary stenting were enrolled between March 2014 and May 2018, with follow-up at 6, 12, 18 and 24 months. In this analysis, all 5438 patients from the original trial were included. A total of 5438 patients were included (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), of which 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was found to be significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference (ARD), 2.7%) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95 CI, 0.58 – 1.00; P=.046; ARD, 1.6%; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy vs aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45 – 1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without diabetes; P for interaction = .99) and any bleeding (HR, 0.65; 95% CI, 0.39 – 1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.12 for those without; P for interaction = .71).

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