The key points of dual antiplatelet therapy are that there is NO mortality benefit for DAPT vs ASA alone; there is a small but significant decrease in coronary stent thrombosis and major adverse cardiac events, but there is also an increased risk of major bleeding.
One trial — the industry-supported, placebo-controlled DAPT study — involved nearly 10,000 patients who had received drug-eluting coronary stents. Patients were randomized to receive dual antiplatelet therapy with aspirin plus a thienopyridine (clopidogrel or prasugrel [Effient]) for either 12 or 30 months. During the 18-month exposure to dual therapy versus aspirin alone, the dual-therapy group experienced significantly lower incidences of stent thrombosis (0.4% vs. 1.4%) and major adverse cardiovascular events (4.3% vs. 5.9%). However, moderate-to-severe bleeding occurred significantly more often in the dual-therapy group (2.5% vs. 1.6%). Cardiovascular-related mortality was similar in the two groups (≈1%), but noncardiovascular-related mortality was significantly higher with dual therapy (1% vs. 0.5%).
In a second randomized trial (the ITALIC study), nearly 2000 recipients of everolimus-eluting coronary stents received dual antiplatelet therapy (aspirin plus clopidogrel) for 6 months and then were randomized to dual therapy or aspirin alone. The trial excluded patients who had tested positive for aspirin resistance. After 6 months of exposure to dual therapy versus aspirin alone, the two groups experienced no significant differences in a composite cardiovascular endpoint or in major bleeding complications. This trial was sponsored by the stent manufacturer.
The third report is a meta-analysis that focused on mortality outcomes in 14 randomized trials in which extended-duration dual antiplatelet therapy (mostly aspirin plus clopidogrel) and aspirin alone were compared. Nine trials involved patients who were randomized after undergoing percutaneous coronary intervention (PCI) and a period of post-PCI dual therapy; the others involved populations with diagnoses such as stroke, peripheral vascular disease, and atrial fibrillation. Trial durations ranged from 6 to 43 months. No difference was noted in all-cause or cardiovascular-related mortality between the extended dual-therapy and non–dual-therapy groups.
Mauri L et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014 Dec 4; 371:2155.
Colombo A and Chieffo A.Dual antiplatelet therapy after drug-eluting stents — How long to treat? N Engl J Med 2014 Dec 4; 371:2225.
Gilard M et al. 6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: The randomized, multicenter ITALIC trial. J Am Coll Cardiol 2015 Mar 3; 65:777.
Elmariah S et al. Extended duration dual antiplatelet therapy and mortality: A systematic review and meta-analysis. Lancet 2014 Nov 16; [e-pub].