SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.
The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by, at the Transcatheter Cardiovascular Therapeutics annual meeting.
“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,”, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.
In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.
At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).
Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).
Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.
“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”
, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”
Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”
The study results were published online at the time of presentation (Circulation 2019 Sep 26..
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.
SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.