By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SOURCE: Hassell ME, et al. Antiplatelet therapy following transcatheter aortic valve implantation. Heart 2015. pii: heartjnl-2014-307053. doi: 10.1136/heartjnl-2014-307053. [Epub ahead of print].
Current guidelines both in the United States and in Europe recommend that patients post-transcatheter aortic valve replacement (TAVR) be treated with 3 to 6 months of dual antiplatelet therapy (DAPT), including low-dose aspirin and a thienopyridine, such as clopidogrel. The use of antiplatelet and antithrombotic medications following TAVR is currently based more on empiricism and experience than on hard data and is at least in part taken from the experience with coronary stenting. Dual antiplatelet therapy is associated with higher rates of bleeding compared with aspirin alone, but evidence supporting its efficacy post-TAVR is sparse.
Hassell et al pooled data from two randomized controlled trials (RCT) and two registry studies, collecting information on a total of 672 TAVR patients who were treated with either DAPT (n = 257) or aspirin alone (n = 415). Patients who were treated with warfarin and those who were treated with clopidogrel alone were excluded. After propensity matching, the ?nal analysis comprised 434 patients, including 235 patients from the matched cohorts and 199 patients from the RCTs.
Net adverse ischemic and thrombotic events, including stroke, were no different between the DAPT and the aspirin monotherapy groups at 30 days. With regard to individual endpoints, no signi?cant difference was observed between all-cause mortality (pooled odds ratio [OR] 0.91; 95% confidence interval [CI], 0.36-2.27; P = 0.83), acute coronary syndrome (pooled OR, 0.5; 95% CI, 0.05-5.51; P = 0.57), and stroke (pooled OR, 1.21; 95% CI, 0.36-4.03; P = 0.75). However, there was a trend toward less life-threatening or major bleeding with aspirin alone. Clinical outcomes were further assessed separately for the included studies. All-cause mortality and acute coronary events were not increased for the aspirin treatment group in both the RCTs and the matched cohorts.
The authors conclude the value of adding a thienopyridine (clopidogrel) to aspirin for post-TAVR patients is in question, and potentially places patients at increased hazard of bleeding without corresponding benefit.
Optimal antiplatelet and antithrombotic therapy following TAVR is an area that clearly warrants further study. The hazard for stroke post-procedure is greatest in the first 24 hours, when approximately 50% of events occur. These early events most likely occur as a result of embolic phenomena from the procedure, and are unlikely to be affected by oral antiplatelet therapy. Subsequently the risk of stroke remains elevated for up to 2 months. The current study suggests that DAPT does not have a significant beneficial effect on the risk of stroke during this period, and likely comes at a cost of increased bleeding.
The landscape for antithrombotics in TAVR has become more complicated recently, with multiple reports showing a small but significant incidence of valve thrombosis detectable by CT imaging, with a subset of these showing clinically significant hindrance of valve function. These cases seem to occur despite dual antiplatelet therapy and tend to be responsive to vitamin K antagonists.
Although the study by Hassell et al is not sufficient to change guidelines, it clearly calls attention to the low level of evidence supporting current recommendations and highlights the need for randomized studies to refine treatment. For now, there is room to individually tailor therapy for these patients. For example, DAPT is not absolutely required for patients with thrombocytopenia and high risk of bleeding, and TAVR patients with atrial fibrillation may do better with warfarin, either alone or in combination with a single antiplatelet agent. Meanwhile, there are no data at all on use of the novel oral anticoagulants in TAVR patients Randomized trials are ongoing and will ultimately provide much-needed evidence for treatment of this population.