The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is uncertain. Although observational studies have suggested DAPT for longer than a year post-PCI reduces ischemic events, other studies suggest longer durations of DAPT confer no benefits despite increased bleeding risk. This randomized controlled trial evaluated patient outcomes with 12-months vs 30-months of DAPT after PCI. A total of 22866 patients after PCI with a drug-eluting stent (approximately 40% in the context of an ACS) were enrolled. After 12 months of standard DAPT (with either clopidogrel or prasugrel alongside aspirin) a total of 9961 patients who had tolerated DAPT without complications and who had not undergone any further procedures were randomly assigned to continue receiving DAPT treatment or to aspirin and placebo for an additional 18 months. The co-primary end-point was stent thrombosis and major adverse cardiovascular events (MACE) with a primary safety end-point of moderate or severe bleeding. Long-term continuation of DAPT significantly reduced the rate of stent thrombosis (0.4% vs. 1.4%; HR, 0.29 [95% CI, 0.17 to 0.48]; P<0.001) and MACE (4.3% vs. 5.9%; HR, 0.71 [95% CI, 0.59 to 0.85]; P<0.001) with an approximate 50% reduction in infarcts related to the non-stented artery (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). This reduction in ischemic events did not translate into all-cause mortality benefit, potentially due to an excess of malignancies in the DAPT group (2.0% vs. 1.5%, HR, 1.36 [95% CI, 1.00 to 1.85]; P=0.052). Bleeding events with extended DAPT were more frequent (2.5% vs. 1.6%, P=0.001).
Conclusions: Extending DAPT to 30 months after PCI reduces the risk of stent thrombosis and myocardial infarction among patients who have already tolerated 12 months of DAPT well. These benefits are balanced by an increased bleeding risk and no overall mortality benefit. Future study may guide approaches to select patients for which the benefits of extended DAPT outweigh the risks.
Summarized by Hussain Contractor and Steven M. Bradley
Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J,Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Lee PV, Rinaldi MJ, Massaro JM; the DAPT Study Investigators. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents. N Engl J Med. 2014 Dec 4;371(23):2155-66.