Patients on dual antiplatelet therapy (DAPT) do no better overall at 30 days after TAVR than those receiving aspirin alone, according to a meta-analysis published online May 6, 2015, ahead of print in Heart. Moreover, aspirin monotherapy may be associated with less major bleeding.

Based on these results, “the additive value of clopidogrel on top of aspirin may be questioned but warrants further investigation,” write Ronak Delewi, MD, of Academic Medical Center (Amsterdam, the Netherlands), and colleagues. “However, a large randomized trial with both ischemic and bleeding clinical endpoints is awaited regarding the efficacy and safety of [aspirin]-only versus DAPT.”

Investigators analyzed pooled patient-level data on 672 TAVR patients (mean age 82 years; 52.8% women) who were treated between 2002 and 2014 with either DAPT (n = 257) or aspirin (n = 415). Those who received vitamin K antagonists—either alone or in addition to antiplatelet drugs—or clopidogrel only were excluded.

Patients were drawn from 2 registry studies and 2 RCTs. Although initially the 2 treatment groups were only “moderately” balanced, the paper notes, propensity-score matching of 235 registry patients resulted in a final “well-matched” cohort of 434 patients (including 199 randomized trial subjects).

At 30 days, there were no differences between patients receiving aspirin monotherapy and those on DAPT for the risk of net adverse clinical events (NACE; all-cause mortality, ACS, stroke, and life-threatening or major bleeding as defined by Valve Academic Research Consortium criteria) or the individual components all-cause mortality and stroke. However, there was a trend toward reduced life-threatening or major bleeding with aspirin (table 1). 

Similar patterns were seen for separate analyses of the pooled randomized trials and of the matched cohort, except that the trend toward lower life-threatening or major bleeding with aspirin was not present in the randomized trials.

Data Question Current Guidelines

“These findings challenge current recommendations and may contribute to improving patient outcomes after [TAVR],” writes Bernard Iung, MD, of Bichat Hospital (Paris, France), in an accompanying editorial.

He notes that the current US guidelines recommending DAPT for 3 to 6 months after TAVR followed by long-term aspirin therapy rely “mainly on the extrapolation of antithrombotic regimens following coronary stenting.” However, he adds, the TAVR and stenting differ in several features that may affect thrombus formation.

In addition, Dr. Iung observes, major bleeding occurs more frequently than stroke early after TAVR, and though lower-profile catheters are reducing vascular complications and the need for a transapical approach, the risk of access-site bleeding remains. Thus, it must still be factored into the choice of antithrombotic regimen, he says.

“Uncertainties regarding the optimal antithrombotic therapy after [TAVR]… illustrate the need for well-designed studies evaluating the risks and benefits of different standardized therapeutic regimens,” he concludes.

One Size Does Not Fit All

“This pooled analysis is a good first attempt to answer an important question,” Philippe Généreux, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview. But since it is underpowered and the primary endpoint is measured at only 30 days, no firm conclusions can be drawn.

Moreover, it is impossible to generalize about the optimal antiplatelet therapy after TAVR, he commented. “Straightforward patients with few comorbidities may not need clopidogrel, though that question remains unresolved. And we may be able to define an appropriate antiplatelet and/or anticoagulant regimen for certain patient subsets, such as those who also have A-fib or CAD or who received a valve-in-valve procedure. But one size does not fit all,” he asserted.

The data “go in the direction of questioning” standard use of DAPT in TAVR patients, observed Josep Rodés-Cabau, MD, of Quebec Heart and Lung Institute (Quebec City, Canada), in a telephone interview with TCTMD. Even considering the very low stroke rate reported in the study, he said, “adding clopidogrel does not seem to have any benefit in terms of protecting against ischemic events.”

Does DAPT Still Make Sense?

Although DAPT made sense in the early days of TAVR when stroke held center-stage, Dr. Rodés-Cabau said, “I’m not sure that clopidogrel plays a major role in protecting against [the emboli and thrombus] of acute stroke, and now we see a clear tendency toward a higher rate of important bleeding events. At some point, the positive risk-benefit ratio associated with DAPT no longer holds—at least in the population we are treating with TAVR today.”

The issue is complicated by the fact that “the A-fib burden in the TAVR population is huge—up to 50%, taking into account A-fib that develops after the procedure,” Dr. Rodés-Cabau reported. These patients require anticoagulation, and the guidelines now recommend adding only 1 antiplatelet drug to warfarin, he said. On the other hand, a substantial number of TAVR patients require DAPT due to prior or concomitant PCI with DES.

The ongoing randomized ARTE trial should provide some help in adjudicating between single and dual antiplatelet therapy, Dr. Rodés-Cabau said, and the single therapy tested in that study—as in most others—is aspirin. “But we can speculate that clopidogrel might be superior in terms of ischemic protection and even for preventing bleeding, especially GI events,” he noted, adding that investigation of newer-generation antiplatelet drugs, such as ticagrelor and prasugrel, would be another “logical move.”

Although many practitioners—especially in the United States—still follow American College of Cardiology guidelines in prescribing 6 months of DAPT, adherence is becoming less strict, Dr. Rodés-Cabau suggested. Therapy is increasingly being tailored to individual patients based on their combined ischemic and bleeding risks as well as their overall clinical background, he said.  

“The reality is that antithrombotic treatment after TAVR is really complex,” Dr.  Rodés-Cabau concluded.

Sources: 
1. Hassell MECJ, Hildick-Smith D, Durand E, et al. Antiplatelet therapy following transcatheter aortic valve implantation. Heart. 2015;Epub ahead of print.
2. Iung B. Antithrombotic therapy after transcatheter aortic valve implantation [editorial]. Heart. 2015;Epub ahead of print.

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