Underdosing of direct oral anticoagulants harmful in AF
Among patients with nonvalvular atrial fibrillation taking direct oral anticoagulants for stroke prevention, those who took an off-label lower dose had greater risk for stroke, MI and death compared with those who took the standard dose, researchers reported at the International Stroke Conference.
The researchers also found that the off-label lower dose did not reduce bleeding risk compared with the standard dose.
Ronen Arbel, PhD, chairperson of the high-tech marketing department at Sapir Academic College in Sderot, Israel, and colleagues analyzed patients from Clalit Health Services who were diagnosed with nonvalvular AF between 2011 and 2016.
During the study period, 3,395 patients were treated with a direct oral anticoagulant at the standard dose and 2,438 patients were treated with a direct oral anticoagulant at an off-label lower dose. Doses were determined based on electronic drug dispensing records.
The primary efficacy endpoint was stroke, MI or death. The primary safety endpoint was major bleeding.
After adjustment for 21 variables including comorbidities, socioeconomic factors and concomitant medications, the reduced-dose group had elevated risk for stroke/MI/death compared with the standard-dose group (adjusted HR = 1.38; 95% CI, 1.13-1.69), according to the researchers.
However, Arbel and colleagues found no difference between the groups in risk for major bleeding (aHR = 1.34; 95% CI, 0.92-1.95).
“In this cohort of patients [with nonvalvular AF] treated in routine clinical practice, off-label lower dose of [direct oral anticoagulants] was associated with a higher risk of mortality, stroke and myocardial infarction and was not associated with a reduced bleeding rate,” the researchers wrote in an abstract. “Our findings provide further support for encouraging adherence to the per-label dosage of [direct oral anticoagulant] therapy.” – by Erik Swain
Arbel R, et al. Abstract 36. Presented at: International Stroke Conference; Feb. 6-8, 2019; Honolulu.
Disclosures: The authors report no relevant financial disclosures.