Are Drug Eluting Stents Worth Triple Therapy?

A pproximately 8% patients undergoing percutaneous coronary intervention are on anticoagulation, which creates difficult choices regarding stent type and antiplatelet use. Drug eluting stents (DES) are usually preferred over bare metal stents (BMS) because of less restenosis and fewer repeat revascularization procedures. However, DES require a longer duration of dual antiplatelet therapy to minimize the chance of stent thrombosis. Typically, this is 6 months of dual antiplatelet therapy for DES compared with 1 month for BMS in patients with stable ischemic heart disease. In a patient already on anticoagulation, adding dual antiplatelet therapy (now triple therapy) poses a significant risk of bleeding: a 2to 3-fold increase per recent studies. The need for triple therapy can be reduced by using a BMS, but is the decreased risk of bleeding worth the increased restenosis risk? Ideally, we would know the benefits and risks of double versus triple therapy, different durations of each strategy, DES versus BMS, and the various permutations. Current European guidelines recommend only 1 month of triple therapy following a DES in those at high risk for bleeding, whereas North American guidelines suggest that triple therapy can be stopped after 3 months; with a switch to dual therapy, this is only a IIb recommendation. However, this is only a IIb recommendation indicating it “may be considered” instead of using the usual 6 months of DAPT. These recommendations are supported, in part, by the ISAR-TRIPLE (Intracoronary Stenting andAntithrombotic Regimen-Testing of a 6-Week Versus a 6-Month Clopidogrel Treatment Regimen in Patients with Concomitant Aspirin and Oral Anticoagulant Therapy Following Drug-Eluting Stenting) study, which compared 6 weeks to 6 months of clopidogrel on top of warfarin and aspirin for those undergoing DES implantation. Among 614 patients, the primary end point of death, myocardial infarction (MI), stent, thrombosis, stroke, or major bleeding at 9 months was slightly, but not significantly, higher in those treated with the shorter 6-weeks of clopidogrel (9.8% versus 8.8%, P=0.63). The secondary end point of Thrombolysis in Myocardial Infarction major bleeding was also slightly, but not significantly, higher in the shorter triple therapy duration arm (5.3% versus 4.0%; P=0.44). Although seemingly small, an absolute 1% difference in death would be important to exclude, arguing for confirmatory studies. The benefits and harms of 1 month of triple therapy as recommended by the European guidelines versus 3 months as suggested by the North American guidelines are even less clear. A recent meta-analysis concluded that triple therapy may offer no benefit over anticoagulation with 1 platelet agent while increasing bleeding. This review of observational studies (N=9) and randomized, controlled trials (n=2) including over 7000 patients compared outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (single antiplatelet therapy and anticoagulant) in patients taking long-term anticoagulants after percutaneous coronary intervention. At a mean 11 months of follow-up,major bleedingwas higher in triple than double therapy (6.6% versus 3.8%; P<0.01). There was no difference in all-cause mortality (relative risk [RR], 0.98; 95% confidence interval [CI], 0.68–1.43), major adverse cardiac events (RR, 1.03; 95% CI, 0.8–1.32), and thromboembolic events (RR, 1.02; 95% CI, 0.49–2.10), though there were nonsignificant trends toward reduced MI (RR, 0.85; 95% CI, 0.67–1.09) and stent thrombosis (RR, 0.77; 95% CI, 0.46–1.3). The studies often included both DES and BMS stents. Thus, it was not clear whether the lack of benefit of triple versus dual therapy for stenting is the same for DES and BMS. Based on this literature demonstrating a clear bleeding risk with triple therapy without a clear benefit, and the guideline recommendations recommending limitation in duration of triple therapy, one would expect that BMS would be used in those with a very high risk of bleeding where there would be less of a need for antiplatelet therapy. However, the results presented in this issue of JAHA suggest that practitioners do not share this concern. Vora et al evaluated over 14 000 patients with atrial fibrillation undergoing acute percutaneous coronary intervention with acute myocardial infarction. Overall, DESwas used in 59% of patients The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the VA Palo Alto Health Care System, Palo Alto, CA. Correspondence to: Paul Heidenreich, MD, MS, Department of Medicine, VA Palo Alto Health Care System, 111c, 3801 Miranda Ave, Palo Alto, CA 94304. E-mail: [email protected] J Am Heart Assoc. 2017;6:e006983. DOI: 10.1161/JAHA.117.006983. a 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.