NEW YORK (Reuters Health) - While non-vitamin K antagonist oral anticoagulants (NOACs) offer safe and effective prevention of stroke or systemic embolism in patients with atrial fibrillation (AF), and simpler administration than warfarin, they too can require careful dose adjustment, U.S. researchers say.
"While these new drugs are relatively easier to manage than warfarin (coumadin), there are still dose adjustments that need to be made for certain patients," co-author Dr. Benjamin A. Steinberg of the University of Utah in Salt Lake City told Reuters Health in an email. "And while the dosing of NOACs will change less frequently than with warfarin, it is important to periodically assess a patient's dose, as factors like renal function and concomitant medications can change."
"Our data suggest most patients are receiving the appropriate dose for stroke prevention in atrial fibrillation," he added. "However, a minority was not, and the use of off-label dosing was associated with worse clinical outcomes."
Off-label NOAC doses were found in about one in eight patients in U.S. community practice, the researchers report.
Further, patients who received higher-than-recommended doses had significantly greater all-cause mortality (adjusted hazard ratio: 1.91). Those receiving lower-than-recommended doses had significantly more cardiovascular hospitalizations (aHR: 1.26) than those prescribed the recommended doses.
In an editorial, Dr. Daniel M. Witt and Dr. Alisyn L. Hansen of the University of Utah College of Pharmacy wrote, "Unfortunately, these results likely underestimate the true magnitude of non-approved NOAC doses in real-world clinical practice and represent an important warning to clinicians prescribing NOACs."
"Oral anticoagulants are high-risk medications," they cautioned, noting that "precise dosing decisions" are needed "regardless of whether warfarin or NOACs are prescribed."
For the study, released online on December 12 by the Journal of the American College of Cardiology, the researchers used data from the ORBIT-AF II registry of patients with AF, which is sponsored by Janssen Scientific Affairs LLC.
The study group included 5,738 patients: 425 treated with dabigatran (7.4%), 3,078 with rivaroxaban (53.6%), and 2,235 with apixaban (39%).
Compared to those whose doses were consistent with the specific NOAC's FDA-approved package insert, patients who received under- or over-doses of NOACs were significantly older (median 79 and 80 years of age vs. 70 years of age, respectively), more likely to be female, and more likely to have high ORBIT bleeding scores.
The researchers noted the difficulty in gauging the intentions of physicians who prescribed higher- or lower-than-recommended NOAC doses. Still, they suggest, "the underlying risks of the cohort suggest potential intentional deviation from approved doses."
They noted, for example, that underdosed patients had significantly higher ORBIT bleeding scores than those given recommended doses. "Physicians may be tailoring the doses of these medications to the specific patient's underlying risk," the report concluded.