ISAR-SAFE: Another Randomized Trial Finds 6 Months of DAPT as Good as 12 Months

CHICAGO, IL—Data from a large randomized trial suggest that 6 months of dual antiplatelet therapy (DAPT) with clopidogrel is noninferior to 12 months of the therapy after drug-eluting stent (DES) implantation. The results of ISAR-SAFE were presented by Stefanie Schulz-Schüpke, MD, of Deutsches Herzzentrum München (Munich, Germany), on November 16, 2014, at the American Heart Association Scientific Sessions.

Patients were recruited from 40 international centers between October 2008 and April 2014. All but 11% received newer-generation DES, predominantly EES (47.5%). The average age was about 67 years, one-quarter of patients had diabetes, and about 40% presented with ACS. Those who remained on clopidogrel 6 months after DES implantation were randomized to 6 more months on the drug (n = 2,003) or a placebo (n = 1,998), and they were followed for 9 additional months (15 months post-intervention). 

At follow-up, rates of the composite of death, MI, definite/probable stent thrombosis, stroke, and TIMI major bleeding (primary endpoint) were low and similar between the 6- and 12-month DAPT groups. Nor were there any differences in efficacy or safety endpoints (table 1).

Table 1. Outcomes at 9 Months Post Randomization by DAPT Duration


The results met the prespecified criteria for noninferiority of shorter vs longer DAPT (P for noninferiority < .001).

Moreover, the findings were consistent across multiple subgroups, with the exception of age > 75 years (P for interaction = .03). 

Dr. Schulz-Schüpke said that the results should be interpreted cautiously because the trial was halted prematurely due to lower-than-expected event rates and slow recruitment.

In a discussion, Gilles Montalescot, MD, PhD, of Centre Hospitalier Universitaire Pitié-Salpêtrière (Paris, France), pointed out that the trial enrolled only about two-thirds of the intended number of patients, the noninferiorty margins were wide, the study treatment was not followed in about 14% of patients, and some patients were lost to follow-up. 

In addition, he noted, ISAR-SAFE looked at net clinical benefit. Yet when investigators evaluate shorter DAPT, the expectation is that it may achieve improved safety—mainly reduced major bleeding—with comparable ischemic protection, and this study was unable to show that.

Nonetheless, Dr. Montalescot said, the results are aligned with those of several prior studies, and DAPT interruption at 6 months may be possible, even in ACS patients, provided they are at low ischemic risk.

  


Source:
Schulz-Schüpke S. Randomized, double-blind trial of 6 versus 12 months of dual antiplatelet therapy after DES implantation (ISAR-SAFE). Presented at: American Heart Association Scientific Sessions; November 16, 2014; Chicago, IL.

 

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ISAR-SAFE: Another Randomized Trial Finds 6 Months of DAPT as Good as 12 Months

Disclosures
  • ISAR-SAFE was supported by Abbott Vascular.
  • Dr. Schulz-Schüpke reports no relevant conflicts of interest.
  • Dr. Montalescot reports receiving research grants from and serving on the speakers’ bureau or advisory board of multiple pharmaceutical and device companies.

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