Long-term Dual-Antiplatelet Treatment After Drug-Eluting Stent Implantation

Amy Leigh Miller, MD, PhD; Joseph Loscalzo, MD, PhD


AccessMedicine from McGraw-Hill 

The relative efficacy and safety of long-term dual-antiplatelet therapy following drug-eluting stent (DES) implantation remains a point of debate. Current guidelines advise that dual-antiplatelet therapy should be administered for 6–12 months following implantation of a DES, but in clinical practice dual-antiplatelet therapy is often continued well beyond a year. Collet and colleagues (2014) studied patients previously followed in the ARCTIC-Monitoring study (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption versus Continuation 1 Year after Stenting), in which French patients were randomized to conventional antiplatelet therapy or platelet function testing, which then guided antiplatelet therapy treatment. Patients who had had no major events in 1 year of follow-up and who remained on aspirin and either clopidogrel or prasugrel were randomized to thienopyridine discontinuation or continuation of dual-antiplatelet therapy for an additional 6–18 months: the ARCTIC-Interruption phase of the trial. The primary endpoint was a composite of myocardial infarction, all-cause death, stroke, transient ischemic attack, urgent coronary revascularization, and stent thrombosis.

A total of 1259 patients were enrolled in ARTIC-Interruption—approximately half of the ARTIC-Monitoring population. The most common reason for exclusion from ARCTIC-Interruption was physician decision. In all, 624 patients were assigned to thienopyridine discontinuation. During follow-up, there was a progressive increase in noncompliance to dual-antiplatelet therapy in the treatment continuation arm, and there was a small rate of crossover from thienopyridine discontinuation to dual-antiplatelet therapy. Analysis was performed according to intention-to-treat. Event rates were low during the 17-month follow-up period, with 1% event rates of myocardial infarction, death, urgent revascularization, stent thrombosis, and stroke. There was no difference between groups in the rate of the composite endpoint or in predefined secondary endpoints. Bleeding events were less frequent in the group no longer taking thienopyridines [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.07–0.91], but there was no significant difference in major bleeding events (HR, 0.15; 95% CI, 0.02–1.20). Mortality rates were higher in patients with high platelet reactivity to adenosine diphosphate while on dual-antiplatelet therapy prior to randomization in ARCTIC-Interruption (HR, 5.07; 95% CI, 1.63–15.76), but there was no relationship between platelet reactivity and ARCTIC-Interruption treatment arm on patient outcomes (p = .78). The authors also performed a meta-analysis, combining data from ARCTIC-Interruption with data from other published studies examining long-term thienopyridine therapy, and found no significant benefit of continued thienopyridine therapy on the combined endpoint or on individual components of the combined endpoint. There was, however, a twofold increase in bleeding event rates with continued dual-antiplatelet therapy.

These results suggest that continued dual-antiplatelet therapy extending beyond 1 year after DES implantation has no significant benefit in low-risk patients, and it carries a risk of increased bleeding events. Unfortunately, no conclusions can be drawn regarding high-risk patients. Further research will be required to determine the utility of long-term thienopyridine therapy in high-risk patients as well as the appropriate duration of such therapy in low-risk patients (e.g., 12 months vs <12 months).