Better post-PCI outcomes with P2Y₁₂ inhibitor than aspirin, also in DM patients
Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial
Introduction and methods
As patients with DM have an increased risk of ischemic events and mortality compared with those with no DM , it is important to select the optimal long-term maintenance antiplatelet therapy in those undergoing PCI. Previously, the HOST-EXAM trial showed that treatment with clopidogrel was associated with a lower incidence of the primary endpoint (a composite of all-cause mortality, nonfatal MI, stroke, readmission due to ACS, and major bleeding) compared with aspirin in patients who underwent PCI and had successfully completed due duration of dual antiplatelet therapy (DAPT) .
Aim of the study
In a post-hoc analysis of the HOST-EXAM trial, the authors investigated clinical outcomes at 24 months in patients who had undergone PCI and were subsequently treated with clopidogrel or aspirin by DM status.
The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Extended Antiplatelet Monotherapy) trial was a prospective, multicenter, investigator-initiated, open-label RCT conducted at 37 centers in Korea. In total, 5438 patients who were maintained on DAPT without clinical events for 6–18 months after PCI was performed with drug-eluting stents were randomized to clopidogrel or aspirin monotherapy. Of these patients, 1860 (34.2%) had DM (925 in clopidogrel arm and 935 in aspirin arm).
For this analysis, the same primary endpoint as that for the original trial was used: a composite outcome of all-cause mortality, nonfatal MI, stroke, readmission due to ACS, and major bleeding (Bleeding Academic Research Consortium (BARC) type 3 or 5) at 24 months. Major secondary endpoints included a thrombotic composite endpoint (defined as cardiac death, nonfatal MI, ischemic stroke, readmission due to ACS, and definite or probable stent thrombosis), major bleeding, and any bleeding (defined as BARC type 2, 3, or 5).
An additional composite endpoint of this post-hoc analysis was MACE, which was a composite outcome of all-cause mortality, MI, and stroke at 24 months.
- In patients with DM, the incidence of the primary composite endpoint was significantly lower in the clopidogrel arm compared with the aspirin arm (6.3% vs. 9.2%; HR: 0.69; 95%CI: 0.49–0.96; P=0.03; absolute risk difference: 2.7%; number needed to treat (NNT): 37). In patients with no DM, the primary endpoint occurred in 5.3% and 7.0%, respectively (HR: 0.76; 95%CI: 0.58–1.00; P=0.046; absolute risk difference: 1.6%, NNT: 63; P for interaction=0.65).
- Of the major secondary endpoints, only the thrombotic composite endpoint showed statistical significance for clopidogrel vs. aspirin in patients with no DM (3.6% vs. 5.3%; HR: 0.68; 95%CI: 0.49–0.93; P=0.02) but not in patients with DM (HR: 0.68; 95%CI: 0.45–1.04; P=0.07; P for interaction=0.99).
- The rates of major bleeding and any bleeding were numerically, albeit nonsignificantly, lower in the clopidogrel arm compared with the aspirin arm in both patients with and with no DM.
- At 24 months, the incidence of MACE was significantly lower in the clopidogrel arm compared with the aspirin arm (3.1% vs. 5.4%; HR: 0.56; 95%CI: 0.35–0.89; P=0.01) in the DM group but not in the no DM group (3.1% vs. 3.0%; HR: 1.04; 95%CI: 0.72–1.52; P=0.83), with significant interaction observed (P for interaction=0.04).
- The risk of the primary composite endpoint was independently associated with increasing age and aspirin monotherapy (compared with clopidogrel monotherapy) in both the DM and no DM groups.
In this post-hoc analysis of the Korean HOST-EXAM trial, clopidogrel monotherapy was associated with a lower rate of the primary composite endpoint at 24 months compared with aspirin monotherapy in patients who had received DAPT after PCI, irrespective of DM status. In addition, clopidogrel decreased the incidence of the thrombotic composite endpoint in patients with no DM and lowered MACE risk in patients with DM.