People with valvular atrial fibrillation (AF) who are new users of direct oral anticoagulants (DOACs) experienced lower risks for ischemic stroke, systemic embolism (SE), and major bleeding compared with new warfarin users. This is according to study results published in the Annals of Internal Medicine.
Increasingly, DOACs are being used in place of warfarin in patients with valvular AF, but effectiveness and safety evidence is lacking. To address this, researchers conducted a retrospective, new-user, propensity score-matched, cohort study to compare safety and effectiveness of DOACS vs warfarin, including the in-class effects of apixaban, rivaroxaban, and dabigatran vs warfarin.
Patients with at least 1 dispensed prescription for either a DOAC or warfarin between 2010 and 2019 were included. Investigators used data from the 12 months prior to the first eligible prescription fill to determine patient characteristics, eligibility, and prior drug use. Patients with an AF diagnosis during the study period, determined via 1 outpatient or 2 inpatient encounters, were also included. To analyze the primary outcomes, DOAC users were matched 1:1 without replacement to a warfarin user.
The primary effectiveness outcome was a composite of ischemic stroke or SE. Primary safety outcome was major bleeding, defined as a composite of gastrointestinal or intracranial bleeding.
The cohort included 46,276 new DOAC users and 34,967 new warfarin users (82% White). Compared with warfarin users, DOAC users were younger (79 vs 82 years of age) and had a higher prevalence of hypertension (88% vs 85%), hyperlipidemia (64% vs 61%), and peripheral vascular diseases (29% vs 22%). Other baseline characteristics were similar.
Following propensity score matching, 28,168 additional new DOAC users and 28,168 new warfarin users were included.
During the course of the study period, prescribing trends generally shifted away from warfarin and toward DOACS. Median follow-up time was 134 and 124 days for DOAC and warfarin users, respectively. Patients were most frequently censored due to treatment discontinuation (74%), end-of-study enrollment (21%), and initiation of or switching to the study comparator (0.8%).
Within the matched sample, 787 patients in the DOAC group and 1211 patients in the warfarin group experienced a stroke or an SE (3.9 vs 6.0 events per 100 person-years; hazard ratio [HR], 0.64; 95% CI, 0.59-0.70). Compared to warfarin, the absolute reduction of stroke or SE probability in DOACs was 0.015 and 0.026 at 6 months and 1 year.
Major bleeding events were less common in the DOAC group compared with the warfarin group (1465 vs 2155 patients, respectively; 7.1 vs 10.6 events per 100 person-years, HR, 0.67; 95% CI, 0.63-0.72). Absolute reduction in the probability of major bleeding with DOAC vs warfarin was 0.019 and 0.035 in 6 months and 1 year of DOAC treatment initiation, respectively.
Sensitivity analysis results were similar to the primary study findings, according to researchers, although CIs for pulmonary valve disease and mitral regurgitation were not statistically significant. Risk for major bleeding events was lower with DOACs compared with warfarin (HR, 0.54; 95% CI, 0.47-0.61).
Compared with patients with valvular AF, those without valvular AF were younger (78 vs 81 years old) and had a lower prevalence of HF (28% vs 47%), anemia (14% vs 21%), and chronic kidney disease (28% vs 36%). In a matched sample, there were 1815 and 2871 incidences of stroke or SE among 76,298 DOAC users and 76,298 warfarin users, respectively (3.1 and 4.5 events per 100 person-years; HR, 0.63; 95% CI, 0.59-0.67).
Study limitations include a lack of data on lifestyle variables, over-the-counter prescriptions, and valvular disease severity, as well as the use of prescription refill data to determine drug exposure and the relatively short follow-up period. Results may not be generalizable to patients with valvular AF who do not have commercial health insurance or those with surgical or transcatheter valve replacement who do not have AF.
“These real-world data suggest that patients with valvular AF who were new users of DOACs had a lower rate of ischemic stroke or [systemic embolism] and major bleeding than new users of warfarin,” the researchers concluded. “These data should guide anticoagulant choices for patients with valvular AF.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Dawwas GK, Diertrich E, Cuker A, Barnes GD, Leonard CE, Lewis JD. Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with valvular atrial fibrillation. A population-based cohort study. Ann Intern Med. Published online March 29, 2021. doi:10.7326/M20-6194