Apixaban Plus P2Y12 Inhibitor Provides Superior Safety vs VKAs in ACS With AF

An apixaban-based antithrombotic regimen and a P2Y12 inhibitor without aspirin is superior to regimens that include vitamin K antagonists (VKA), aspirin, or both in terms of safety and similar in terms of efficacy in patients with atrial fibrillation (AF) who have acute coronary syndrome (ACS) managed either medically or with percutaneous coronary intervention (PCI), according to research results published in Circulation.

Using data from the AUGUSTUS trial (ClinicalTrials.gov identifier: NCT02415400), investigators evaluated the safety and efficacy of the antithrombotic regimens used in the trial in 3 prespecified, mutually exclusive patient subgroups: AF and ACS treated medically, AF and ACS undergoing PCI, and AF and stable coronary artery disease undergoing elective PCI.

Briefly, the AUGUSTUS trial was an international, randomized clinical trial utilizing a 2×2 factorial design in which patients with AF and ACS and/or undergoing PCI were randomly assigned to either apixaban or vitamin K antagonists (VKA) and aspirin or placebo.

The current study included data from 4614 patients from 492 sites in 33 countries. Of these patients, 61.2% had ACS; 38.8% underwent elective PCI. Among those with ACS, 39% were treated medically, whereas the other 61% of patients underwent PCI. Overall, patients with ACS were younger, more likely to be women, and had a higher incidence of cardiovascular risk factors.

Just over 8% of patients in the medically managed ACS group treated with apixaban or VKA experienced the primary safety end point of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant nonmajor (CRNM) bleeding, compared with 12.8% in the ACS PCI group and 15% in the elective PCI group. Investigators noted a lower bleeding risk with apixaban compared with VKA across all 3 groups (hazard ratios [HRs] 0.44, 0.68, and 0.82, respectively).

In terms of secondary efficacy outcomes, risks for death or hospitalization were lower among apixaban-treated patients in the medically managed ACS group (HR 0.71) compared with the ACS PCI and elective PCI groups (HRs 0.88 and 0.87, respectively). No difference in the risk for death or ischemic events in apixaban vs VKA was noted.

In aspirin- or placebo-treated patients, the primary safety end points of ISTH major or CRNM bleeding were noted in 8.4% of patients in the medically managed ACS group, 12.8% in the ACS PCI group, and 14.8% in the elective PCI group. A higher risk of bleeding with aspirin than with placebo was consistent across all 3 groups (HRs 1.49, 2.02, and 1.91, respectively). No difference in risk for death, hospitalization, or ischemic events was noted.

Across all 3 subgroups, the percentage of patients reaching the primary safety end point was lowest among patients treated with apixaban and placebo and highest among those receiving VKA and aspirin. Cumulative incidence of hospitalization or death was lower among those treated with apixaban and placebo across all 3 groups as well.

One study limitation is the underpowered results for the 3 subgroups; another is the study’s lack of address of the optimal treatment duration for combined anticoagulation and antiplatelet treatment.

“[A]nticoagulation with apixaban, at the dose labeled for stroke prevention in patients with AF, combined with a P2Y12 inhibitor without aspirin should be considered in patients with AF and ACS, managed medically or with PCI, or those with AF undergoing elective PCI.”

Disclosure: This clinical trial was supported by Bristol-Myers Squibb and Pfizer, Inc. Multiple authors report affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Windecker S, Lopes RD, Massaro T, et al; Augustus Investigators. Antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome treated medically or with percutaneous coronary intervention or undergoing elective percutaneous coronary intervention: insights from the AUGUSTUS trial [published online September 26, 2019]. Circulation. doi:10.1161/CIRCULATIONAHA.119.043308