Clinical impact of dual antiplatelet therapy use in patients following everolimus-eluting stent implantation: insights from the SEEDS study

Abstract

Background: Studies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up.

Methods: The SEEDS study is a prospective, multicenter study, where patients (n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up.

Results: DAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment.

Conclusions: Prolonged DAPT use was not associated with improved clinical safety. The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).

Trial registration: ClinicalTrials.gov NCT01157455.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1

The use of dual antiplatelet therapy (DAPT) in the SEEDS study. DAPT was used in the majority of patients at 1 month and 6 months (a, b, c). Two-third of patients was taking DAPT at 12 months, and one-third of patients at 24 months (c). The reduced proportion of DAPT use at each time point was mostly due to complete script of clopidogrel.

Figure 2

Clinical outcomes of patients treated with EES at 2-year follow-up. Clinical outcomes were presented with Kaplan–Meier curves in patient with small vessel, long lesion, and multi-vessel disease undergoing EES implantation at 2-year follow-up (a, b). Def/prob: Definite/probable; EES: Everolimus-eluting stent; MI: Myocardial infarction; NACE: Net adverse clinical event; ST: Stent thrombosis; TVF: Target vessel failure.

Figure 3

Cumulative effect of DAPT on clinical safety endpoints. Adjusted cox regression analyses using DAPT as a time-dependent covariate showed that the use of DAPT was not associated with significantly reduced risk of NACE (a) and composite endpoint of all-cause death/MI/stroke; (b) Cumulative effect analyses revealed a reduced beneficial effect of DAPT use on clinical safety at follow-up. DAPT: Dual antiplatelet therapy; MI: Myocardial infarction; NACE: Net adverse clinical event.

Figure 4

(a) Status of DAPT at the time of ST and major bleeding events. No patient who had DAPT interruption experienced ST at 12 months, and only one patient between 1- and 2-year; (b) There was a high frequency of major bleeding events occurred in patients receiving DAPT treatment. DAPT: Dual antiplatelet therapy; ST: Stent thrombosis.