The inquire of of how finest to take care of patients with atrial fibrillation after a profitable transcatheter aortic valve implantation (TAVI or TAVR) stays unsettled, with the bid component Xa inhibitor edoxaban (Savaysa, Daiichi Sankyo) proving noninferior to warfarin for a composite clinical endpoint however at the associated fee of additional bleeding within the ENVISAGE-TAVI AF trial.
The threat for International Society on Thrombosis and Haemostasis main bleeding turned into elevated 40% with edoxaban (9.7 vs 7.0 per 100 particular person-years; hazard ratio [HR], 1.40), which didn’t originate noninferiority (P = .93). The variation turned into pushed by extra gastrointestinal (GI) bleeding with edoxaban (HR, 2.03; 95% CI, 1.28 – 3.22) together with one fatal match.
Both the vital composite efficacy endpoint of ranking negative clinical events (NACE) and main bleeding, on the other hand, had been decrease within the 46.4% of patients whose each day dose of edoxaban turned into diminished from 60 mg to 30 mg.
“Subanalyses to additional explore this finding imply that patients enjoyable dose adjustment criteria and patients with out concomitant oral antiplatelet remedy might per chance moreover very well be cheap, acceptable candidates for edoxaban in step with attenuating bleeding effects, and we shall be conducting additional investigations on this topic,” senior author George Dangas, MD, PhD, Icahn School of Treatment at Mount Sinai, Original York Metropolis, concluded.
The outcomes had been reported at this time time in a Sizzling Line session at the digital European Society of Cardiology (ESC) Congress 2021 and published simultaneously on-line within the Original England Journal of Treatment.
Dangas identified that edoxaban turned into noninferior to warfarin for stroke or systemic embolism and nick encourage bleeding dangers in a popular population of patients with atrial fibrillation (AF) within the ENGAGE AF-TIMI 48 trial, which didn’t include patients undergoing TAVI. Then once more, results are much less decided with unusual oral anticoagulants (NOACs) in patients undergoing TAVI, the build roughly a third of patients contain AF or accomplish it after the direction of.
In the sleek ATLANTIS trial, apixaban (Eliquis, Pfizer/Bristol-Myers Squibb) turned into now not superior to popular worship a composite clinical raze result however didn’t expand bleeding, whereas the GALILEO trial turned into stopped upfront as a result of a elevated price of demise, thromboembolic events, and severe bleeding with rivaroxaban (Xarelto, Bayer/Janssen).
Look for discussant and ATLANTIS investigator Jean-Philippe Collet, MD, PhD, Sorbonne Université Pitié-Salpêtrière Properly being facility, Paris, France, acknowledged ENVISAGE-TAVI AF is the most uncomplicated lumber NOAC trial, demonstrating noninferiority against nutrition Ok antagonists (VKAs), however that the elevated threat for bleeding limits patient eligibility.
“The transition of NOACs to agree to is tricky because whether or now not NOACs are the total identical after TAVI appears to be like now not going. NOAC security depends upon on concomitant use of antiplatelet remedy and dosing,” he concluded. “Whether it’s time to replace the pointers is doubtful.”
In the end of the panel discussion, Collet acknowledged patient characteristics had been very different in ATLANTIS and that they warned investigators to now not proceed triple remedy as a result of the phobia of bleeding, primarily in step with the GALILEO results, which “doubtlessly explains why now we contain this type of distinction by manner of combination with antiplatelet remedy.”
Alec Vahanian, MD, University Paris-Descartes, France, one of many chairs of the newly updated European valvular heart illness guiding theory, identified that within the wake of ATLANTIS, “folks are doing what they honestly feel is trustworthy for the time being and plenty are now not bridging to 1 more anticoagulant after TAVI, that is to dispute, restarting a NOAC. But as you already know, in case you write a guiding theory, you love evidence.”
He agreed with Dangas and the panel that “many questions can contain to be answered sooner than we transfer to a guiding theory recommendation… Maybe whereas you pool your files you shall be ready to resolution in a larger manner this tough inquire of. So let’s explore in just a few years.”
An Aged AF Inhabitants With an OAC Indication
ENVISAGE-TAVI AF enrolled 1426 patients with AF and a demonstration for an oral anticoagulant (OAC) after profitable TAVI within the outdated 5 days at 173 centers. Patients had been randomly assigned to 60 mg/day of edoxaban or popular VKA management along with discretionary twin antiplatelet remedy for as a lot as three months after TAVI, or single antiplatelet remedy indefinitely. Launch air the united states, edoxaban dosing will be diminished if patients had renal failure or low physique weight or had been taking concomitant P-glycoprotein inhibitors.
The population turned into aged (common age, 82 years), shut to half had been female, larger than 80% had congestive heart failure, and the mean Society of Thoracic Surgeons threat ranking turned into 4.9.
After a median agree to-up of 548 days, the price of NACE — a composite of all-cause demise, myocardial infarction, ischemic stroke, systemic embolism, valve thrombosis, or main bleeding — turned into 17.3 per 100 particular person-years within the edoxaban community and 16.5 per 100 particular person-years with warfarin (HR, 1.05; P = .01 for noninferiority).
Superiority sorting out of edoxaban for efficacy turned into now not performed because noninferiority and superiority weren’t met for main bleeding.
There were no differences between the edoxaban and VKA groups for all-cause demise or ischemic stroke. No valve thrombosis turned into reported in either community.
Panelist Renato Lopes, MD, Duke University Medical Center, Durham, North Carolina, acknowledged meta-analyses contain shown a 58% expand in GI bleeding with NOACs over warfarin, seemingly because NOACs are metabolized to the GI tract moderately than the liver. “So finding a 40% expand in GI bleeding turned into a cramped bit expected” within the ENVISAGE-TAVI AF cohort.
Even supposing there are known pharmacologic differences between the NOACs, together with mechanism of movement and renal excretion, in popular, as an anticoagulant, these agents are extra identical than different, important Lopes. That acknowledged, it be crucial for clinicians to salvage what he’s been calling the “antithrombotic sweet device.”
“That manner that for every patient, together with the direction of the patient underwent, it be crucial to salvage the factual dose, the factual combination of agents, for the factual duration that will give us the finest low cost in ischemic events at a minimal mark of bleeding, which we all know is by no manner going to be zero,” Lopes acknowledged. And, “this trial provides to the associated fee of evidence with high quality of evidence to higher repeat what this sweet device shall be.”
Session chair Stephan Windecker, MD, Bern University Properly being facility, Inselspital, Bern, Switzerland, remarked that “it appears to be like appropriate love within the PCI [percutaneous coronary intervention] discipline, much less is extra and one crucial ingredient appears to be like to be antiplatelet remedy.”
The inquire of sponsor, Daiichi Sankyo, contributed to the trial invent, habits, and oversight; files prognosis; and manuscript writing. Dangas reported evaluate contracts with Daiichi Sankyo and Bayer. Coauthor disclosures are listed within the paper.
European Society of Cardiology (ESC) Congress 2021. Equipped August 28, 2021.
N Engl J Med. Published on-line August 28, 2021. Abstract
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