Outcomes With Warfarin in Atrial Fibrillation: Individual Patient Data Analysis From Four Randomized Trials

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Warfarin is a key oral anticoagulant for stroke prevention in atrial fibrillation (AF).
• Updated outcome data are crucial, especially in regions with limited direct oral anticoagulant (DOAC) access.
• Risk stratification is essential for optimizing anticoagulation therapy.

Purpose of the Study:

• Identify predictors of adverse outcomes in patients treated with warfarin.
• Evaluate the performance of the TIMI-AF risk score in predicting outcomes.
• Compare the efficacy and safety of standard-dose DOACs versus warfarin across different risk strata.

Main Methods:

• Analysis of individual patient data from 58,634 participants in 4 randomized trials.
• Utilized trial-stratified Cox models to assess net clinical outcomes (NCO).
• NCO defined as all-cause death, disabling/fatal stroke, or intracranial/fatal bleeding.

Main Results:

• Older age, male sex, impaired kidney function, lower BMI, vitamin K antagonist-naïve status, and nonparoxysmal AF predicted increased NCO risk.
• Annualized NCO rates were 3.5% (low-risk), 7.6% (intermediate-risk), and 12.9% (high-risk) by TIMI-AF score.
• Standard-dose DOACs reduced NCO across all risk strata, with modest absolute benefit in low-risk patients.

Conclusions:

• Identified key predictors of adverse warfarin outcomes.
• Standard-dose DOACs demonstrated benefit across the risk spectrum for AF patients.
• Warfarin remains a reasonable choice for low-risk patients, particularly where DOAC access is limited.