Clopidogrel Superior to Aspirin for Long-term Antiplatelet Monotherapy After PCI

Clopidogrel monotherapy was associated with a lower rate of adverse events following percutaneous coronary intervention (PCI) than aspirin in patients both with and without diabetes, according to a post hoc analysis of the HOST-EXAM randomized clinical trial.

Conducted to specifically investigate the association of diabetes with the known risks of long-term antiplatelet monotherapy and comparing aspirin and clopidogrel, this secondary analysis demonstrated that at 24 months after PCI, persons with diabetes receiving clopidogrel had a 31% lower risk of the trial’s primary composite endpoint, ie, all-cause death, nonfatal myocardial infarction (MI), stroke, readmission due to acute coronary syndrome (ACS), and major bleeding, compared with those receiving aspirin.

Patients with diabetes, which is regarded as a prothrombotic state, are at greater risk of ischemic events as well as mortality following PCI, making optimal antiplatelet therapy choice critical to secondary prevention for them, wrote authors in JAMA Cardiology. Randomized trial data, regarding an optimal selection beyond the acute phase after PCI among persons with diabetes are limited, however.

“The results of our study suggest that clopidogrel could be considered over aspirin for long-term maintenance antiplatelet therapy after PCI in both patients with and without diabetes.”

The original prospective, randomized, open-label Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis–Extended Antiplatelet Monotherapy (HOST-EXAM) trial enrolled 5438 participants between March 2014 and May 2018. All participants had maintained dual antiplatelet therapy (DAPT) without clinical events for 6-18 months after PCI with drug-eluting stents. These patients were randomized in a 1:1 ratio to receive 75 mg clopidogrel once-daily or 100 mg aspirin once-daily.

Patients with diabetes...are at greater risk of ischemic events as well as mortality following PCI, making optimal antiplatelet therapy choice critical to secondary prevention for them. Randomized trial data, regarding an optimal selection beyond the acute phase after PCI among persons with diabetes are limited, however.

The HOST-EXAM investigators reported that use of clopidogrel was associated with a 26% relative reduction in risk of the trial’s primary composite endpoint and a 26% lower risk of major bleeding events.

The primary outcome of interest in this post-hoc analysis was the same as for the original trial, defined as a composite of all-cause death, nonfatal MI, stroke, readmission attributable to ACS, and major bleeding (Bleeding Academic Research Consortium [BARC] type 3 or 5). The trial included a secondary thrombotic endpoint, which was a composite of cardiac death, nonfatal MI, ischemic stroke, readmission attributable to ACS, and definite or probable stent thrombosis, and a bleeding endpoint, defined as BARC type 2, 3, or 5. Investigators conducted subgroup analyses by the presence of diabetes.

The HOST-EXAM cohort had a mean age of 63.5 years and 25.5% were women. Of the 5438 participants, 34.2% (n=1860) had diabetes. Approximately 98% of participants completed the 24-month follow-up.

Post hoc analysis findings

The investigators reported similar findings for those with and without diabetes. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in participants with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69 [95% confidence interval [CI], 0.49-0.96]; P=.03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76 [95% CI, 0.58-1.00]; P=.046; ARD, 1.6%; NNT, 63; P_interaction=.65).

They found further that diabetes was not associated with a difference in benefit observed with use of clopidogrel monotherapy relative to aspirin for the thrombotic composite endpoint (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; P for interaction = .99) or the bleeding endpoint with BARC 2, 3, or 5 (HR, 0.65 [95% CI, 0.39-1.09] for patients with diabetes vs HR, 0.74 [95% CI, 0.48-1.13] for those without; 
P_interaction=.71).

“In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes,” concluded investigators “Although not significant due to insufficient statistical power in each group, the association of clopidogrel with reduced risk compared with aspirin was consistent for both thrombotic and bleeding outcomes in both the diabetes and no diabetes groups.”

Reference: Rhee TM, Bae JW, Park KW, et al. Aspirin vs clopidogrel for long-term maintenance after coronary stenting in patients with diabetes: a post-hoc analysis of the HOST-EXAM Trial. JAMA Cardiol. 2023;10.1001/jamacardio.2023.0592. Published online April 12, 2023. doi:10.1001/jamacardio.2023.0592