Oral Anticoagulation, but Not DAPT, Protects TAVR Valves in FRANCE-TAVI Registry

August 25, 2018

MUNICH — Oral anticoagulation (OAC) in patients discharged after a successful transcatheter aortic valve replacement (TAVR) seemed to protect the valve implant from functional deterioration over the ensuing months yet was associated with an increased risk for death, in an analysis based on a French registry study.

The increased mortality risk of about 18% associated with OAC was ostensibly independent of whether there was atrial fibrillation (AF) in the multivariate analysis. But researchers question whether OAC really had such a bad effect on survival in the cohort study, noting that AF was a much stronger predictor of mortality and, not surprisingly, most patients receiving OAC also had AF.

Other predictors of poor survival after TAVR in the analysis based on the FRANCE-TAVI registry included being male and having chronic renal failure.

Importantly, dual antiplatelet therapy (DAPT) had no apparent effect on mortality and also didn't seem to protect the valve implant from functional deterioration, reported Jean-Philippe Collet, MD, PhD, Pitié-Salpêtrière Hospital, Paris, France, here at the European Society of Cardiology (ESC) Congress 2018.

DAPT is recommended after TAVR, but with few clinical trial data for guidance, OAC, a single antiplatelet agent, or OAC plus antiplatelets is sometimes used depending on patient characteristics, such as whether there is accompanying coronary disease or AF, Collet told  theheart.org | Medscape Cardiology.

But the growing proportion of patients undergoing TAVR who also have chronic ischemic disease and AF is a high-risk population in whom it may be best to avoid antiplatelet therapy while OAC is administered, to keep the risk of bleeding down, he said.

Collet is also senior author on study's publication, which appeared in the Journal of the American College of Cardiology, with lead author Pavel Overtchouk, MD, from the same center, to coincide with his presentation at the ESC sessions.

Little is known about the appropriateness of OAC or antiplatelet therapy after TAVR, commented Patrick Serruys, MD, PhD, from Erasmus Medical Center, Rotterdam, the Netherlands, as comoderator of the session featuring Collet's presentation.

The study's association between OAC and increased mortality was "quite convincing," he said, but not very independent as it was probably driven by its association with AF. Patients receiving OAC showed significantly less valve dysfunction, he noted, and OAC in practice goes hand in hand with AF, "which is well known as a killer."

In an interview, Collet agreed that the mortality increase with OAC is "probably" driven by associated AF, which was present in 70.8% of the patients receiving OAC. But the current analysis is not from a randomized trial and has other limitations, so it remains unknown whether the observed mortality increase on OAC actually comes from its association with AF.

The analysis followed 12,804 patients who underwent TAVR at 48 centers in France from 2013 to 2015, including 11,469 who survived to hospital discharge and were followed for mortality; valve implant function was followed in 2555 with sufficient documented echocardiographic data.

In the mortality analysis, 33.4% of the 11,469 patients were discharged on OAC. In multivariate analysis, with a follow-up averaging about 500 days, treatment with neither aspirin nor clopidogrel showed a significant association with survival.

Table 1. Independent Predictors of Mortality in the FRANCE-TAVI Registry

Predictors Hazard Ratio (95% Confidence Interval) P Value
Male sex 1.63 (1.44 - 1.84) <.001
History of AF 1.41 (1.23 - 1.62) <.001
Chronic renal failure 1.37 (1.23 - 1.53) <.001
Moderate-severe prosthetic-valve regurgitation 1.28 (1.11 - 1.50) .001
NYHA class III or IV heart failure 1.28 (1.14 - 1.46) <.001
Discharge oral anticoagulation 1.18 (1.04 - 1.35) .013

 

Of the 2555 patients with least two echocardiographic evaluations, 5.5% were found to have bioprosthetic valve dysfunction (BVD), defined as prosthetic valve gradient increased by at least 10 mm Hg or a new gradient at least 20 mm Hg.

In multivariate analysis, smaller TAVR prosthesis size and a history of TAVR were the strongest predictors of BVD, while discharge on OAC and TAVR catheter access by a route other than the femoral artery were protective against BVD.

Collet proposed that non–femoral-artery access for TAVR was a marker of diffuse atherosclerotic disease that included the femoral artery and therefore was associated with reduced risk.

Table 2. Independent Predictors of Risk for Bioprosthetic Valve Dysfunction

Endpoints OR (95% CI) P Value
Prosthesis size ≤ 23 mm 3.43 (2.41 - 4.89) <.001
Prior TAVR 2.96 (1.15 - 7.64) .025
Chronic renal failure 1.46 (1.03 - 2.08) .034
Discharge oral anticoagulation 0.54 (0.35 - 0.82) .005
Non–femoral-artery TAVR approach 0.53 (0.28 - 1.02) .049

OAC in the current analysis usually consisted of vitamin K antagonists (VKAs), Collet said. He speculated that the good safety record of the newer-generation non-VKA oral anticoagulants demonstrated in trials of nonvalvular AF will carry over to the post-TAVR setting.

He pointed to a crop of ongoing randomized trials exploring the safety and effectiveness of OAC with both VKA and non-VKA agents and of DAPT in patients who have undergone TAVR. Of special interest, he said, would be comparisons of OAC vs DAPT in TAVR patients without conventional OAC indications, such as AF.

Among those trials is the ongoing ATLANTIS, which is evaluating the non-VKA apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) vs standard care in patients with successful TAVR, regardless of whether they have a current OAC indication. It similarly includes GALILEO, which is comparing rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals) to DAPT after TAVR.

Other ongoing trials in this arena include ENVISAGE, looking at edoxaban (Savaysa/Lixiana, Daiichi Sankyo) after TAVR in patients with AF; POPULAR, which is exploring post-TAVR DAPT; AVATAR, testing antiplatelets on top of OAC in patients with an OAC indication; and AUREA, comparing OAC to antiplatelet therapy after TAVR.

Collet reports the following disclosures for the past 2 years: research grants or honorarium from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Fédération Française de Cardiologie, Lead-Up, Medtronic, Merck Sharpe & Dohme, Sanofi-Aventis, and WebMD. Disclosures for the other authors are in the report. Serruys recently disclosed serving as a consultant to and/or receiving fees or other honoraria from Abbott, Biosensors, Medtronic, and others.

European Society of Cardiology (ESC) Congress 2018. Presentation 72. Presented August 25, 2018.

J Am Coll Cardiol. Published online August 25, 2018. Abstract

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