P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial

Abstract

Importance: P2Y12 inhibitor monotherapy after dual antiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent.

Objective: To investigate whether P2Y12 inhibitor monotherapy after 3 months of DAPT was noninferior to 12 months of DAPT following PCI with a drug-eluting stent.

Design, setting, and participants: The Short-Term Dual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinical trial was conducted from December 15, 2017, through December 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals in South Korea. Patients who underwent successful PCI with bioabsorbable polymer everolimus-eluting stents were enrolled.

Interventions: Patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of DAPT (n = 693).

Main outcomes and measures: The primary outcome was a net adverse clinical event, a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index PCI. The major secondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%.

Results: Of the total 1452 eligible patients, 65 patients were excluded before the 3-month follow-up, and 1387 patients (mean [SD] age, 63.0 [10.7] years; 1055 men [76.1%]) were assigned to P2Y12 inhibitor monotherapy (n = 694) or DAPT (n = 693). Between 3 and 12 months of follow-up, the primary outcome (using Kaplan-Meier estimates) occurred in 9 patients (1.7%) in the P2Y12 inhibitor monotherapy group and in 16 patients (2.6%) in the DAPT group (absolute difference, -0.93 [1-sided 95% CI, -2.64 to 0.77] percentage points; P < .001 for noninferiority). For the major secondary outcomes (using Kaplan-Meier estimates), major adverse cardiac and cerebrovascular events occurred in 8 patients (1.5%) in the P2Y12 inhibitor monotherapy group and in 12 patients (2.0%) in the DAPT group (absolute difference, -0.49 [95% CI, -2.07 to 1.09] percentage points; P = .54). Major bleeding occurred in 1 patient (0.2%) in the P2Y12 inhibitor monotherapy group and in 5 patients (0.8%) in the DAPT group (absolute difference, -0.60 [95% CI, -1.33 to 0.12] percentage points; P = .10).

Conclusions and relevance: In patients with coronary artery disease undergoing PCI with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations.

Trial registration: ClinicalTrials.gov Identifier: NCT03447379.

Figure 1.. Participant Flowchart

DAPT indicates dual antiplatelet therapy. ^aStudy sites were not required to provide screening logs. Data on the reasons for ineligibility were not available. ^bOutcomes of patients who were lost to follow-up or withdrew consent were included at the point of final contact. Time-to-event measurements were censored on the last contact date.

Figure 2.. Time-to-Event Curves for the Primary Outcomes

A net adverse clinical event was defined as a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) or major adverse cardiac and cerebrovascular events. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. Vertical dashed line indicates 3-month point (after which 1 group received P2Y12 inhibitor monotherapy [P2Y12i] and the other received dual antiplatelet therapy [DAPT]).

Figure 3.. Subgroup Analyses for the Primary Outcome Between 3 and 12 Months After the Index Procedure

Squares indicate hazard ratios (HRs), with horizontal lines indicating 95% CIs. ACS indicates acute coronary syndrome; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CAD, coronary artery disease; CCS, chronic coronary syndrome; DAPT, dual antiplatelet therapy; LV, left ventricular; P2Y12i, P2Y12 inhibitor monotherapy.