Antiplatelet agents added to anticoagulation with warfarin and other vitamin K antagonists was associated with more major bleeding but not better outcomes following transcatheter aortic valve replacement (TAVR) in patients with atrial fibrillation (Afib), a multicenter observational study showed.
On multivariable adjustment, major or life-threatening bleeding was more likely in Afib patients on both warfarin and antiplatelet agents (24.4% versus 14.9% for those on vitamin K antagonists alone, HR 1.85, 95% CI 1.05-3.28). Josep Rodés-Cabau, MD, of Canada’s Quebec Heart & Lung Institute, and colleagues reported the findings in JACC: Cardiovascular Interventions.
Outcome rates were largely similar between combo and monotherapy groups over a median of 13 months:
- Stroke (5.2% versus 5%, HR 1.25, 95% CI 0.45-3.48)
- Major adverse cardiovascular events (16.3% versus 13.9%, HR 1.33, 95% CI 0.75-2.36)
- Death (19.2% versus 22.8%, HR 0.93, 95% CI 0.58-1.50)
- Cardiovascular death (9.8% versus 9.9%, HR 1.09, 95% CI 0.54-2.22)
“These findings suggest that prescribing an antiplatelet agent to Afib patients already anticoagulated post-TAVR is unlikely to confer added clinical benefit while potentially being harmful,” the researchers wrote.
“Recommendations pertaining to antiplatelet treatment after TAVR in patients in sinus rhythm stem from a consensus of experts and are based essentially on the assumption that stent implantation requires dual-antiplatelet treatment for at least 6 months,” Thierry Lefèvre, MD, of Institut Cardiovasculaire Paris Sud in France, commented in an accompanying editorial.
In light of Rodés-Cabau’s study and other ongoing investigations on new anticoagulation agents such as apixaban (Eliquis) and dabigatran (Pradaxa), Lefèvre suggested that “one can anticipate that current guidelines will be completely overhauled within the next 2 to 3 years.”
For their study, Rodés-Cabau and colleagues included patients who had undergone TAVR. Participants were divided among those who just got monotherapy with vitamin K antagonists (n=101); those who got dual antithrombotic therapy with aspirin or clopidogrel (Plavix) on top (n=463); and a final group of patients who got triple therapy consisting of warfarin, clopidogrel, and aspirin (n=57).
“The number of study participants was relatively low, especially within the triple therapy group,” the authors acknowledged.
Among other limitations of their investigation, “confounding by indication could be present, and patients receiving any antiplatelet therapy could present higher vascular risk profile than patients under vitamin K antagonist monotherapy. For this reason, the extrapolation of the results of our study in patients with concomitant coronary artery disease should be made with caution despite the statistical adjustments performed.”
“Despite the limitations of performing a subanalysis from an observational study, our results suggest that patients receiving double therapy and concomitant aspirin harbored the highest risk of bleeding, whereas patients receiving clopidogrel presented with a … bleeding risk [similar to that of] patients receiving monotherapy.”
In lieu of aspirin, “these results suggest that adding clopidogrel to vitamin K antagonists in those patients with a mandatory indication for antiplatelet therapy (i.e., recent stenting) could represent a relatively safer strategy in those patients already anticoagulated undergoing TAVR,” according to Rodés-Cabau’s group.
“If an oral anticoagulant must be combined with an antiplatelet treatment, it seems preferable to choose clopidogrel rather than aspirin,” agreed Lefèvre.
The editorialist pointed out that the study “indirectly raises the issue of short- or midterm anticoagulation therapy after TAVR for patients in sinus rhythm.”
“Indeed, although rare cases of valve thrombosis successfully treated with anticoagulant agents have been reported, several studies published since 2015 have shown that systematic follow-up using multislice computed tomography after TAVR revealed the presence of partial thrombosis of one or several cusps in 10% to 15% of cases, which, though asymptomatic and successfully treated with anticoagulant medications, could potentially increase the risk for valve thrombosis or stroke,” the editorialist wrote.
Rodés-Cabau disclosed receiving research support from Edwards Lifesciences, Medtronic, and St. Jude Medical.
Lefèvre reported proctoring for Edwards Lifesciences.
JACC: Cardiovascular Interventions
Altisent OA, et al “Warfarin and antiplatelet therapy versus warfarin alone for treating patients with atrial fibrillation undergoing transcatheter aortic valve replacement” JACC Cardiovasc Interv 2016; 9: 1706-17.
JACC: Cardiovascular Interventions
Lefèvre T “Anticoagulation treatment after transcatheter aortic valve replacement: striking the right balance” JACC Cardiovasc Interv 2016; 9; 1718-20.