Current treatment guidelines recommend that patients undergoing drug-eluting stent (DES) percutaneous coronary intervention (PCI) take dual antiplatelet therapy (DAPT) consisting of aspirin plus an adenosine diphosphate receptor inhibitor for at least 12 months after the procedure [Levine GN et al. J Am Coll Cardiol. 2011]. The Safety and Efficacy of Six Months Dual Antiplatelet Therapy After Drug-Eluting Stenting [ISAR-SAFE; Byrne RA et al. Am Heart J. 2009] trial was designed to determine whether 6 months of DAPT treatment was noninferior to 12 months. Patients undergoing DES PCI received open-label DAPT (aspirin plus clopidogrel) for 6 months and then were randomized 1:1 to aspirin plus blinded clopidogrel for 6 additional months (12-month group) or aspirin plus placebo (6-month group). Stefanie Schulz-Schüpke, MD, Deutsches Herzzentrum München, Munich, Germany, presented the results of the ISAR-SAFE trial.

This was an investigator-initiated, international, randomized, double-blind, placebo-controlled trial that recruited patients at 40 centers from October 2008 to April 2014. Eligible patients took clopidogrel for 6 months after DES placement. Patients were excluded if they had signs or symptoms of ischemia or lesions requiring revascularization, had active bleeding or a history of intracranial bleeding, had an STEMI or non-STEMI in the 6 months since DES placement, had a previous stent thrombosis (ST), had a DES in the left main coronary artery in the index PCI, were taking oral anticoagulants, or were planning surgery within 6 months that required the discontinuation of antiplatelet therapy.

The primary end point was a composite of death, myocardial infarction (MI), ST, stroke, or TIMI major bleeding at 9 months after randomization (15 months after the index PCI). Secondary end points were the individual components of the primary end point. The investigators planned to enroll 6000 patients, but the study was terminated early, when 4000 patients were randomized. This decision was made by the Data Safety Monitoring Board and the Steering Committee based on a lower-than-expected event rate (1.6% actual vs 10% estimated) and slow recruitment.

A total of 4005 patients were randomized, 1998 in the 6-month group and 2007 in the 12-month group. Demographic characteristics were similar between the 2 groups. The mean age was 67 years, the mean body mass index was 27 kg/m², 19% were women, 24% had diabetes, 15% were active smokers, and 25% had a prior MI. The 6-month group had an event rate of 1.5% in the primary composite end point compared with 1.6% in the 12-month group (observed difference, 0.1%; upper limit of 1-sided 95% CI, 0.5%; P _{Noninferiority} < .001). Other key results are presented in Table 1.

A subgroup analysis suggested that older patients may benefit from 6 months of DAPT, whereas younger patients may benefit from 12 months of DAPT (Table 2). No other factors had a significant interaction.

Although no differences in key clinical outcomes were seen between the 2 arms, Dr Schulz-Schüpke noted that these findings should be interpreted carefully due to the early termination of the study and the lower-than-anticipated event rates.