CHICAGO – Atrial fibrillation patients treated with an anticoagulant plus four or more other medications had significantly more bleeding complications than did those on fewer medications in a retrospective study.
“This is the first study examining polypharmacy in patients with nonvalvular atrial fibrillation,” Dr. Jonathan P. Piccini said at the American Heart Association Scientific Sessions. The main consequence is, “We should do everything we can to reduce the number of medications a patient receives,” he said.
Dr. Jonathan P. Piccini
His exploratory, retrospective analysis of data from more than 14,000 patients enrolled in an anticoagulant treatment trial showed that atrial fibrillation patients on an oral anticoagulant and taking a total of 10 or more medications concurrently had a 46% increased rate of a major bleed or clinically relevant nonmajor bleed. Patients taking five to nine medications had a 17% increased rate for this primary bleeding endpoint. Both increases were statistically significant, reported Dr. Piccini, a cardiologist at Duke University in Durham, N.C. Major bleeds alone were 90% higher in patients on at least 10 drugs and 47% higher in patients on 5-9 total drugs, compared with those on 4 or fewer, also statistically significant differences.
“Increasing medication use was associated with an increased risk of bleeding but not stroke,” he said. In addition, because the data came from a large trial that had compared the new oral anticoagulant rivaroxaban (Xarelto) with warfarin, the analysis was able to show that this polypharmacy effect was similar regardless of which anticoagulant patients took.
Polypharmacy was common among the 14,264 patients (average age, 73 years) enrolled in the trial, as 51% were on 5-9 drugs and 13% were on 10 or more drugs, with a minority of 36% forming the comparator group taking 4 or fewer medications.
The analysis used data collected from 14,264 patients enrolled in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial, which was designed as a pivotal trial comparing the safety and efficacy of the new oral anticoagulant rivaroxaban with warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (N. Engl. J. Med. 2011;365:883-91). Dr. Piccini and his associates assessed various measures of bleeding as well as strokes, vascular deaths, and all-cause deaths in the patients by their number of concomitant medications based on data collected at baseline when patients entered the trial. The relative hazard rates the investigators calculated were adjusted for all “clinically important covariates,” but Dr. Piccini acknowledged that residual confounding accounted for by the adjustments likely remained.
All-cause death was also significantly increased in patients taking at least 10 (a 43% increase) or 5-9 drugs (a 25% increase), compared with patients on 4 or fewer drugs. But the rate of stroke or nonstroke embolism was not significantly increased among patients on five or more drugs. The combined rate of stroke, nonstroke embolism, and vascular death was a statistically significant 25% higher in patients on at least 10 drugs, compared with those on 4 or fewer drugs, but there was no significant increase in patients on 5-9 drugs.
The link between higher numbers of concomitant medications and an increased bleeding rate likely has two explanations, Dr. Piccini said. It could happen because the drugs themselves promote bleeding, and because the need to prescribe multiple drugs is a marker for patients who are sicker and have more comorbidities and a higher underlying risk of bleeding.
ROCKET AF was sponsored by Janssen and Bayer. Dr. Piccini has been a consultant to and has received research funding from Janssen, Bayer, and several other companies.
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