PARIS — Edoxaban (Savaysa) plus a P2Y12 inhibitor was non-inferior to the standard triple treatment (P2Y12 inhibitor, aspirin, and vitamin K antagonist or VKA) used to prevent bleeding among patients with atrial fibrillation (AF) following coronary stenting, the ENTRUST-AF PCI trial found.
Clinically relevant non-major or major bleeding events occurred in 17% of patients treated with the edoxaban-P2Y12 inhibitor combination versus 20% of patients on the triple regimen (HR 0.83, P=0.0010 for non-inferiority), reported Pascal Vranckx, MD, PhD, of Hasselt University in Belgium, and colleagues.
The composite of stroke, cardiovascular death, definite stent thrombosis or myocardial infarction, and systemic embolic events occurred in about 6% of patients on triple therapy and about 7% in the edoxaban group (HR 1.06, 95% CI 0.71-1.59), they reported at the European Society of Cardiology (ESC) congress and simultaneously in The Lancet.
“[In] patients with atrial fibrillation who underwent PCI [percutaneous coronary intervention], the edoxaban-based dual antithrombotic therapy was noninferior for bleeding compared with VKA-based triple antithrombotic regimen, without significant differences in ischaemic events,” said co-author Andreas Goette, MD, of St. Vincenz Hospital of Paderborn in Germany, during an ESC press conference.
Patients with AF who need an oral anticoagulant may also need PCI and a stent implantation if they have stable coronary artery disease (CAD) or have acute coronary syndrome (ACS), noted Kurt Huber, MD, of Wilhelminen Hospital in Vienna, who was not involved in the study. Treating patients with AF and CAD or ACS presents concern regarding the use of combination of antithrombotic drugs in cases needing PCI, he added.
The ENTRUST-AF PCI trial, along with AUGUSTUS, PIONEER AF-PCI, and REDUAL have addressed whether reducing triple therapy to dual therapy, by only using an oral anticoagulant along with one antiplatelet, would reduce bleeding complications and have a similar ischemic event rate, Huber highlighted. These trials have looked at each oral anticoagulant including apixaban (Eliquis), dabigatran (Pradaxa), edoxaban, and betrixaban (Bevyxxa), he added.
Triple therapy consists of an oral anticoagulant, aspirin, and usually clopidogrel, Huber noted. “This triple therapy might lead to severe bleeding complications in much higher frequency than if you compare it to monotherapy with an oral anticoagulant or an antiplatelet drug,” Huber told MedPage Today.
Triple therapy “should no longer be used for patients who are a candidate for a NOAC [novel oral anticoagulants],” emphasized Christopher Granger, MD, of Duke University in Durham, North Carolina, who was not involved in the study.
Aspirin use along with clopidogrel should be used for a relatively limited period of time, Granger told MedPage Today. “This is where the controversy comes in; we’re not sure how long it should be used.”
“I think [what] the guidelines and the North American consensus document will end up saying is to use … for the typical patient, somewhere between a few days, maybe 1 week, and maybe 1 month of aspirin when we use a NOAC and clopidogrel after, let’s say, coronary stenting,” Granger stated.
“The data shows us that at least 2 weeks of aspirin — at least two weeks of triple therapy before you skip aspirin — are important to avoid acute thrombotic events, and then you can quite safely skip aspirin. This will have no impact on ischemic events, but it clearly could have a reduction of bleeding events,” Huber said.
For patients with greater thrombotic potential, like those with ACS or undergoing complex PCI, extending the duration of aspirin use, or considering more potent P2Y12 inhibition, can be decided by taking into account the individual risk of ischemic event or bleeding, noted Davide Capodanno, MD, PhD, of the University of Catania in Italy, and Dominick Angiolillo, MD, PhD, of the University of Florida in Jacksonville, in an accompanying Lancet editorial.
For the trial, 755 participants were randomized to the triple regimen and 751 to the edoxaban regimen at 186 sites in 18 countries. Mean age was about 70 and about 26% were women. From PCI to randomization, the median time was 45.1 hours. All patients had undergone successful PCI with stent placement and would require anticoagulant treatment for AF for at least 1 year.
Patients were randomized within 5 days following PCI to either a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor at investigators’ discretion) for 12 months plus 60 mg of edoxaban taken once daily or to standard therapy with a P2Y12 inhibitor in combination with a vitamin K antagonist and aspirin of 100 mg once daily for 1 to 12 months.
If one or more factors including body weight that was ≤60 kg (about 133 lbs), concomitant use of specified potent P-glycoprotein inhibitors, or creatinine clearance of 15 to 50 mL/min were present, then the edoxaban dose was lowered to 30 mg per day.
Limitations included that the trial only enrolled patients undergoing PCI, involved a relatively small sample size, had a landmark analysis at 14 days that was not pre-specified, and did not include information on the duration for aspirin use in the warfarin plus P2Y12 inhibitor plus aspirin arm, noted ESC discussant Renato Lopes, MD, MHS, PhD, also of Duke.
Lopes pointed out that, considering the study design, it is unclear if the numerical reductions in bleeding after 2 weeks resulted from aspirin avoidance or edoxaban use.
ENTRUST-AF PCI was funded by Daiichi Sankyo. Some co-authors are company employees.
Vranckx disclosed relevant relationships with AstraZeneca, Terumo, Daiichi Sankyo, and Bayer. Goette disclosed support from Josef-Freitag-Stiftung and Deutsche Herzstiftung. Co-authors disclosed multiple relevant relationships with industry.
Huber disclosed no relevant relationships with industry.
Capodanno disclosed relevant relationships with, and support from Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi. Angiolillo disclosed relevant relationships with, and support from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, The Medicines Company, CeloNova, St Jude Medical, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, and Renal Guard Solutions.