Physicians' Academy for Cardiovascular Education

Nonrecommended dosing of NOACs associated with higher risk of all-cause mortality in AF

Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants

Literature - Camm AJ, Cools F, Virdone S, et al. - J Am Coll Cardiol 2020;76:1425–36;

Introduction and methods

Novel oral anticoagulants (NOACs) are approved in most countries in the world, but differences exist with regard to regulatory authority-specific guidance that takes into account baseline characteristics of the patients, such as kidney function, low body weight, age, bleeding risk and drug-drug interactions. Country-specific guidelines vary for the different NOACs [1-3] and confusion about correct prescription may lead to inappropriate dosing (both underdosing and overdosing).

This study examined the patterns of NOAC prescription with regard to dosing, the impact of NOAC dosing on rate of events at 2-year follow-up and predictors of underdosing in newly diagnosed AF patients in the GARFIELD-AF registry.

The GARFIELD-AF registry enrolled patients with AF diagnosed within the previous 6 weeks, with at least 1 risk factor for stroke and no valvular disease. For this analysis patients from cohort 3 to 5 were enrolled (n=34926). Those not on any NOAC, with more than 1 NOAC type simultaneously, or no information on starting date, no CKD stage information, unavailable dose information were excluded, leaving 10426 patients. Rules of prescription for the NOACs rivaroxaban, apixaban, edoxaban and dabigatran were reviewed for definition of recommended dosing, underdosing or overdosing. 4491 (43.1%) Patients received rivaroxaban, 3290 (31.6%) apixaban, 2359 (22.6%) dabigatran and 286 (2.7%) edoxaban.

Main results


Most AF patients who were enrolled in the GARFIELD-AF registry received appropriate dosing of NOACs. Underdosing was not uncommon though, but overdosing rate was low. Nonrecommended doses and underdosage were associated with increased risk of mortality, but not with increased risk of stroke-related death. Nonrecommended dosing was not associated with bleeding compared to those who received recommended doses, but those who received underdosing had reduced bleeding compared to those with recommended doses.


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Find this article online at J Am Cardiol Coll

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