Low Adherence to All Oral Anticoagulants the Norm in Atrial Fib

Pam Harrison

March 08, 2016

ROCHESTER, MN — Fewer than half of patients with atrial fibrillation adhere to their anticoagulant regimen in a real clinical-practice setting, even if prescribed one of the new oral anticoagulants (NOACs) rather than a vitamin-K antagonist such as warfarin, a cohort study suggests[1]. The NOACs have been touted as more convenient to take, and adherence to them was better than warfarin adherence in the retrospective analysis, but there was still a substantial shortfall.

"We found that adherence to anticoagulation therapy was suboptimal. During a median of 1.1 years of follow-up, fewer than half of the patients took the medications consistently," note the authors, led by Dr Xiaoxi Yao (Mayo Clinic, Rochester, MN), in their report published in the February 2016 issue of the Journal of the American Heart Association. "We see that adherence to anticoagulation continues to be a challenge, regardless of the medication used."

The investigators used administrative claims from a large US insurance database to identify 64,661 patients with AF who had initiated treatment with warfarin or one of three NOACs between November 2010 and December 2014. Each patient's CHA2DS2-VASc was calculated based on nine possible points, higher scores indicating a higher risk of stroke. Almost 90% of patients had a CHA2DS2-VASc score of 2 or more.

The anticoagulant was warfarin in 59%, apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) in 6%, dabigatran (Pradaxa, Boehringer Ingelheim) in about 16%, and rivaroxaban (Xarelto, Bayer/Johnson & Johnson) in 19%, according to the group. End points included first hospital admission for either ischemic stroke or systemic embolism and major gastrointestinal (GI) bleeding, intracranial hemorrhage, or bleeding from other sites.

At the yearlong median follow-up, 47.5% of patients taking one of the NOACs had adhered to treatment for 80% or more of the study interval. That was modestly although signifcantly better than adherence among patients taking warfarin, in whom just 40.2% had 80% or more days covered by anticoagulation (P<0.001).

After adjustment for confounders, the predicted probability of patients being adherent varied by the anticoagulant taken as well as by stroke risk category, with those in the highest-risk category having slightly more consistent adherence than those at lower risk.

Adherence to Anticoagulant Agents in Multivariate Analysis

CHA2DS2-VASc score Apixaban (%) Dabigatran (%) Rivaroxaban (%) Warfarin (%) P (all NOACs pooled vs warfarin)
0 or 1 40.6 28.6 30.8 25.2 <0.001
2 or 3 51.9 46.9 48.8 37.3 <0.001
≥4 54.1 48.7 50.1 42.0 <0.001

During follow-up, 1150 patients were admitted for either an ischemic stroke or a systemic embolism. The incidence rate was lowest at 0.33 out of 100 person-years among patients with a CHA2DS2-VASc score of 0 to 1 and highest at 1.82 per 100 person-years in those with a CHA2DS2-VASc score of 4 or more.

"No significant effect was found between nonadherence and the risk of stroke in patients with a CHA2DS2-VASc score of 0 or 1," Yao notes.

In contrast, the risk of stroke in patients who did not take an oral anticoagulant for 6 months or more was 2.7-fold greater among those with a CHA2DS2-VASc score of 2 to 3 compared with those who were nonadherent for less than a week.

Similarly, the risk of stroke was 3.6-fold higher in patients with a CHA2DS2-VASc score of 4 or more among patients who missed their anticoagulant for 6 months or more compared with those who missed their anticoagulant for less than 1 week.

On the other hand, "nonadherence to an oral anticoagulant was related to lower risk of bleeding," study authors point out.

For those who did not take an anticoagulant for 6 months or more, the risk of bleeding was 54% lower for those in the lowest-stroke-risk group (score 0–1); 32% lower for those in the middle-risk group (score 2–3), and 21% lower for those in the highest-risk group (score ≥4).

Furthermore, the risk of having an intracranial hemorrhage was 77% lower in the lowest-risk group (score 0–1) for patients who did not take any anticoagulant for 3 months or more compared with patients who were nonadherent for less than a week.

In contrast, no significant association was seen between the risk of intracranial hemorrhage and nonadherence in those with a CHA2DS2 -VASc score of 2 or more.

"Among patients with CHA2DS2-VASc score ≥2, better adherence was associated with lower stroke risk and a relatively small increase in bleeding risk—in particular, no significant increase in intracranial bleeding," Yao confirms.

"Conversely, among patients with CHA2DS2-VASc score 0 or 1, better adherence was associated with no significant change in the risk of stroke but an increased risk of bleeding," she adds, concluding:

"In our study, because of the low adherence rates, it is likely the nonadherence in routine clinical practice was less the result of missing pills but rather failure to refill medications, resulting in discontinuation or long gaps between refills."

The study was supported by Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery. Yao had no relevant financial relationships; disclosures for the coauthors are listed in the article.


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