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Reference: DAPT trial (N Engl J Med 2014 Dec 4;371(23):2155) (level 2 [mid-level] evidence)
Dual antiplatelet therapy is recommended for at least 12 months in patients having a percutaneous coronary intervention with a drug-eluting stent to reduce the risk of restenosis (Circulation 2011 Dec 6;124(23):e574-651). Extending the duration of DAPT may decrease the risk of stent thrombosis, but evidence on the efficacy of DAPT for > 1 year has been inconsistent (Am J Cardiol 2014 Jul 15;114(2):236, Am J Cardiol 2013 Feb 15;111(4):486). A recent randomized trial compared 12 vs. 30 months of treatment with thienopyridine (clopidogrel or prasugrel) plus aspirin (DAPT) in 9,961 patients (mean age 62 years, 75% male) having drug-eluting stent implantation.
All patients were treated with DAPT for 12 months before being randomized to a thienopyridine vs. placebo for an additional 18 months while aspirin therapy was continued indefinitely. Only patients adherent to therapy and without major adverse events during the first 12 months were eligible for randomization. Of the eligible patients, 50.9% had at least 1 risk factor for stent thrombosis. Between study months 12 and 30, extended 30-month DAPT was associated with reduced stent thrombosis (0.4% vs. 1.4%, p < 0.001 NNT 100) and reduced major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%. p < 0.001 NNT 63) compared to standard 12-month DAPT. Extended 30-month DAPT was not without risks, however, as extended DAPT was associated with increased risk of moderate-to-severe bleeding (2.5% vs. 1.6%, p = 0.001 NNH 111). On further analysis, an increased risk of bleeding was observed for moderate bleeding only, with no significant differences in severe bleeding between groups. All-cause mortality during the 18-month randomization period was 2% in patients with extended DAPT vs. 1.5% with placebo (p = 0.05). Increased risk of stent thrombosis and myocardial infarction were observed for the first 3 months after thienopyridine discontinuation, regardless of treatment duration.
This trial suggests that increasing the duration of DAPT to 30 months after implantation of a drug-eluting stent decreases the risk of stent thrombosis as well as major cardiovascular and cerebrovascular events. Extended DAPT therapy was associated with a small increase in all-cause mortality, but this finding was driven by an increase in cancer-related deaths in patients with a cancer diagnosis before randomization. The difference in all-cause mortality between groups was no longer significant if patients with cancer diagnoses before randomization were excluded from analysis. Concerns have previously been raised about whether prasugrel promotes the development or progression of cancer (Arch Intern Med 2010 Jun 28;170(12):1078). Overall, there appears to be a cardiovascular benefit with extended treatment, but patients with pre-existing cancer may not see an overall benefit.
For more information, see the Antiplatelet and anticoagulant drugs for coronary artery disease topic in DynaMed.