DAPT Substudy: No Apparent Benefit of Long-term DAPT in BMS Patients
Patients treated with BMS receive no benefit from continuing dual antiplatelet therapy (DAPT) past 12 months if no major bleeding occurs, according to an analysis of the DAPT Study published in the March 17, 2015, issue of the Journal of the American Medical Association. However, the researchers acknowledge, the BMS cohort may have been underpowered to identify a difference in outcomes.
Results from both the original DAPT Study and this subanalysis were presented at the 2014 American Heart Association Scientific Sessions in Chicago, IL. The overall study found substantial reductions in stent thrombosis and MACCE (driven by a decrease in MI) with 30 vs 12 months of DAPT in almost 10,000 DES-treated patients from August 2009 to July 2011. However, an increase in moderate/severe bleeding was seen with prolonged thienopyridine use.
For the substudy, researchers led by Laura Mauri, MD, MSc, of Brigham and Women’s Hospital (Boston, MA), looked at 1,687 patients who received BMS and either 12 months (n = 845) or 30 months (n = 842) of aspirin and a thienopyridine (clopidogrel or prasugrel [Effient; Eli Lilly/Daiichi Sankyo]) during the same study period. Patients in the short-term group were given a placebo for the period between 12 and 30 months.
While DES-treated patients were more likely to have histories of diabetes, hypertension, and previous PCI and have longer lesions with smaller reference vessel diameters, those treated with BMS were more likely to present with STEMI or NSTEMI and were more likely to have thrombus in the treated lesion.
MACCE, Stent Thrombosis Similar Between Groups
Among BMS-treated patients, there were no differences between short-term and extended DAPT in the incidence of stent thrombosis or MACCE (death, MI, and stroke) between 12 and 30 months after the index procedure. However, prolonged therapy yielded more BARC type 2, 3, or 5 bleeding events and a trend toward increased GUSTO bleeding (table 1).
Severe and fatal bleeding events were rare and did not differ between treatment groups.
Post hoc analysis suggested that BMS-treated patients were less likely than DES-treated patients to derive protection from continued DAPT against stent thrombosis (HR 0.49 vs 0.29; P = .42 for interaction) and MACCE (HR 0.92 vs 0.71; P = .32 for interaction).
Rates of stent thrombosis and MACCE in the overall cohort, including both DES- and BMS-treated patients, were lower with continued thienopyridine (P < .001 for both endpoints).
Absence of Interaction Merits Cautious Interpretation
“The major limitation of the BMS randomized comparison of DAPT duration is small sample size and lack of power, which limits the interpretability of the findings,” Dr. Mauri and colleagues say. They add that “an adequately powered randomized BMS cohort would require approximately 8,000 additional patients, which was practically not feasible” given the prevailing use of DES in contemporary practice.
“The lack of apparent treatment interaction between DES and BMS supports the combined analysis of treatment effects of continued duration of therapy independent of stent type,” the investigators write.
However, they caution, due to the lack of power, “true differences in treatment effect size may not have been detected, and any interpretation that continued thienopyridine therapy beyond 1 year… may prevent ischemic events independent of stent type (DES or BMS) should be considered hypothesis generating.”
Kereiakes DJ, Yeh RW, Massaro JM, et al. Antiplatelet therapy duration following bare metal or drug-eluting coronary stents: the Dual Antiplatelet Therapy randomized clinical trial. JAMA. 2015;313:1113-1121.
- DAPT Study Shows Benefit of Long-Term Treatment After DES Implantation
- ZEUS Published: ZES With Personalized DAPT Bests Bare-Metal Stent in ‘Uncertain’ DES Candidates
- Extending Clopidogrel Past 1 Year Improves Outcomes in DES, But Not BMS Patients
- The DAPT Study was sponsored by the Harvard Clinical Research Institute and funded by Abbott, Boston Scientific, Bristol-Myers Squibb/Sanofi Pharmaceuticals partnership, Cordis, Daiichi Sankyo, Eli Lilly, Medtronic, and the US Department of Health and Human Services.
- Dr. Mauri reports receiving grants from Abbott, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cordis, Eli Lilly, Daiichi Sankyo, Medtronic, and Sanofi-Aventis and personal fees from Biotronik, Medtronic, and St Jude.