SAN FRANCISCO – Continued thienopyridine therapy beyond 1 year in patients treated with an everolimus-eluting stent was associated with significantly lower rates of myocardial infarction and thrombosis, but an increased risk of bleeding, study results have shown.
Dr. James B. Hermiller of St. Vincent´s Medical Group, Indianapolis, presented the data at the Transcatheter Cardiovascular Therapeutics annual meeting. The results were also published online (JACC: Cardiovasc Interv 2015. doi: 10.1016/j.jcin.2015.10.001).
In a post hoc analysis of a subset of patients from the DAPT (Dual Antiplatelet Therapy) study, Dr. James B. Hermiller Jr. and his colleagues evaluated major adverse cardiac and cerebrovascular event (MACCE) and bleeding events in 4,703 patients who’d been treated with an everolimus-eluting stent and 1 year of therapy with thienopyridine and aspirin before being randomly assigned to 18 additional months of the same DAPT, or an additional 18 months of aspirin plus placebo.
Dr. James B. Hermiller Jr.
The original DAPT Study, a multisite, international, double-blinded, trial of 25,682 coronary stent patients was done to evaluate the efficacy and safety of various combinations of types of drug-eluting stents plus DAPT.
Results from the subanalysis of the everolimus-eluting stent group were that at 12-30 months post percutaneous intervention, those given additional DAPT had significantly reduced thrombosis (P =.04) and MI (P =.01), compared with aspirin-only controls, but the DAPT test cohort had more moderate to severe bleeding complications (P = .01). Composite death, MI, or stroke rates were also better in the placebo group (P = .42), Dr. Hermiller said at the meeting sponsored by the Cardiovascular Research Foundation.
The continuous-DAPT group had a stent thrombosis rate of 0.3%, compared with 0.7% of the 12-month–only group (hazard ratio, 0.38). The rate of MI in the test group was 2.11% vs. 3.2% in controls (HR, 0.63). The DAPT test group had a 2.5% rate of increased bleeding vs. 1.3% in the placebo group (HR, 1.79).
Patients in the subanalysis were typically older than across all original study groups – typically, men in their early 60s who were more likely to have been treated with clopidogrel (84.4% vs. 48.2%), and to have a slightly lower body mass index, although they were still obese (30.3 vs. 30.8 kg/m2).
The subanalysis group also had a slightly higher rate of history of cancer (P less than .001), a data point that Dr. Hermiller and his coauthors noted in the study accounted for the DAPT continuation group’s significantly increased all-cause mortality, compared with the placebo group (2.2% vs. 1.1%, P =.02).
In an interview, Dr. Spencer B. King, president of the Heart and Vascular Institute of St. Joseph’s Health System in Georgia, and comoderator of the session where the data were presented, also emphasized this finding’s importance, since “cancer increases bleeding risk and is one of the conditions in which prolonged DAPT should usually be avoided.”
The most frequent cause of noncardiovascular death in the DAPT-continuation group was cancer: 18 of the test group vs. 4 in the placebo group (P =.002); 3 of the study group’s cancer deaths involved bleeding. Overall, the second most common cause of death was bleeding, which occurred more in the DAPT test group than in placebo (P = .04).
Dr. Hermiller and his coauthors wrote that the therapeutic window for continued thienopyridine therapy “may be narrow” since the number needed to treat to benefit for stent thrombosis was 235 over 18 months. For MI it was 98. The number needed to treat to harm for moderate or severe bleeding was 84.
“Therefore, meticulous assessment of bleeding risk should always impact decisions regarding thienopyridine therapy duration.”
However, they also noted that current data suggest a net benefit to continuing therapy with absolute reductions in stent thrombosis or MI of about 0.2%, an effect that was exceeded in the everolimus-eluting stent patient subset.
Dr. Hermiller is a consultant for Abbott Vascular, Boston Scientific, Medtronic, and St. Jude Medical. The study also was sponsored by the Harvard Clinical Research Institute Harvard Clinical Research Institute and funded by Abbott, Boston Scientific Corporation, Cordis Corporation, Medtronic, Bristol-Myers Squibb Company/Sanofi Pharmaceuticals Partnership, Eli Lilly and Company, and Daiichi Sankyo Company Limited and the U.S. Department of Health & Human Services.
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