PCI in Patients on Warfarin: Do We Need Dual Antiplatelet Therapy?
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco.
Source: Dewilde WJ, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial. Lancet 2013;381:1107-1115.
Many patients need to take long-term oral anticoagulants (OAC) for indications such as atrial fibrillation (AF) or mechanical prosthetic valves. When these patients also require percutaneous coronary intervention (PCI), the concurrent requirement for dual anti-platelet therapy (DAPT) plus OAC increases the risk of serious bleeding. It is not known whether aspirin remains necessary in combination with clopidogrel plus warfarin in these patients. To address this question, Dewilde and colleagues performed a multicenter, randomized, controlled trial in 15 centers in Belgium and the Netherlands. From November 2008 to November 2011, adults receiving OAC and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. The secondary endpoint was a composite of death, myocardial infarction (MI), stroke, target-vessel revascularization, and stent thrombosis (according to the Academic Research Consortium criteria).
A total of 573 patients were enrolled and 1-year data were available for 279 (98.2%) patients assigned double therapy and 284 (98.3%) assigned triple therapy. Mean ages were 70.3 ± 7.0 years and 69.5 ± 8.0 years, respectively. Compliance at 1 year was approximately 80% with clopidogrel in both groups and 67% with aspirin in the triple therapy group. Bleeding episodes were seen in 54 (19.4%) patients receiving double therapy and in 126 (44.4%) receiving triple therapy (hazard ratio [HR] 0.36; 95% CI, 0.26-0.50; P < 0.0001). In the double therapy group, six (2.2%) patients had multiple bleeding events, compared with 34 (12.0%) in the triple therapy group. Eleven (3.9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9.5%) patients in the triple therapy group (odds ratio from Kaplan-Meier curve 0.39; 95% CI, 0.17-0.84; P = 0.011). The lower bleeding rate with double therapy was consistent across the subgroups of age, sex, presentation of an acute coronary syndrome, indication for OAC, and stent type. Interestingly, there was no excess of ischemic outcomes in the double therapy group. The rates of the combined secondary endpoint were 11.1% in the double therapy group and 17.6% in the triple therapy group. After correction for baseline characteristics, the HR remained similar (0.56, 95% CI, 0.35-0.91). The authors conclude that use of clopidogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events.
Commentary
As patients age, the likelihood of developing disease that requires OAC or DAPT increases. Thus, it is quite frequent to encounter patients who have indications for both. There have been surprisingly few data on this patient cohort to date, and this study by Dewilde and colleagues addresses this key issue. The study is strengthened by its randomized, controlled, multicenter design with adjudication of all clinical events by a blinded clinical endpoint committee. However, it was an open-label trial and that may introduce some potential confounding. The study was powered to assess bleeding endpoints, not ischemic endpoints. However, the rate of ischemic events numerically favored the double therapy group. The authors caution that this requires further validation, but there is no signal that suggests a downside to withholding aspirin in this patient group. How can we explain lower bleeding and lower thrombotic endpoint rates in the double therapy group in this study? Thrombin itself is an activator of platelets, so the use of OAC not only inhibits thrombin, but also secondarily has some antiplatelet effect. The authors suggest that this may lessen the effect of inhibiting cyclo-oxygenase with aspirin.
There are several limitations that should be pointed out in interpreting this study. The open-label study may introduce bias, as mentioned before. Second, there are some incomplete data. In particular, the time spent in therapeutic range on warfarin is not reported and may have a significant influence on bleeding. Also, there were baseline differences between groups, but it is not clear which differences were statistically significant and were accounted for in the multivariable analysis. Third, the results are not stratified by the patient’s bleeding risk. It would have been helpful to know if there were certain clinical predictors that could guide us in which subgroups to use this approach. Fourth, we now have ticagrelor and prasugrel, and their role in conjunction with OAC is still to be defined. Despite these limitations, this study suggests that for our patients requiring OAC and DAPT, it may be reasonable to withhold aspirin and just use OAC + clopidogrel. My approach is to assess each patient’s individual bleeding risk and to consider withholding aspirin if their bleeding risk is high.
Many patients need to take long-term oral anticoagulants (OAC) for indications such as atrial fibrillation (AF) or mechanical prosthetic valves.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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