Poor Adherence to Dabigatran Common, Linked with Worse Clinical Outcomes

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Approximately 1 in 4 patients with nonvalvular atrial fibrillation (A-fib) who are prescribed dabigatran do not take it as directed and are therefore at increased risk for adverse clinical events, according to a Veterans Affairs (VA) study published online April 7, 2014, ahead of print in the American Heart Journal.

P. Michael Ho, MD, PhD, of VA Eastern Colorado Health Care System (Denver, CO), and colleagues enrolled 5,376 patients with nonvalvular A-fib who were prescribed dabigatran between October 2010 and September 2012 at VA hospitals nationwide. Dabigatran adherence was measured in proportion of days covered (PDC; total number of nonhospitalized days in which dabigatran was supplied divided by the observation time interval) with nonadherence defined as PDC < 80%.

One-Quarter of Patients Found Nonadherent

After a median follow-up period of 244 days and a median number of 5 refills, 27.8% of patients were found to be nonadherent. These patients were more likely to be younger and less likely to be Caucasian compared with those classified as adherent. Adherent patients had a lower burden of depression, drug abuse, and alcohol abuse and were less likely to be on concomitant clopidogrel compared with nonadherent patients.

Median PDC at 1 year was 94%. Among nonadherent patients, the median number of gaps was 2 with a median gap length of 24 days. Moreover, 23% of patients had a gap in dabigatran use lasting longer than 30 days.

Death and stroke occurred at a rate of 5% over the study period. Multivariable analysis found that a decrease in PDC by 10% was associated with an increased risk of all-cause death and stroke (primary endpoint). There was a consistent association for the individual outcome of stroke, but it was not significant due to the low number of total strokes. Additionally, adherence was not associated with nonfatal bleeding events or MI (table 1).

Table 1. Association Between Adherence and Outcomes

 

Number of Events

Adjusted HR
(95% CI)a

All-Cause Mortality and Stroke

247

1.13 (1.08-1.19)

Stroke

31

1.13 (0.97-1.33)

Nonfatal Bleeding

96

1.04 (0.94-1.13)

MI

20

0.97 (0.78-1.21)

aPer 10% decrease in PDC.

Prior warfarin use was associated with better adherence to dabigatran (OR 1.25; 95% CI 1.12-1.37).

Closer Follow-up Necessary

“The results of this study support that initiating dabigatran in atrial fibrillation patients in of itself is not adequate to reduce the stroke risk,” Dr. Ho and colleagues write. “Since dabigatran and the other new oral anticoagulation agents do not require routine laboratory monitoring, they may require closer clinical follow-up to ensure adequate adherence.”

According to the researchers, causes of nonadherence to dabigatran could include:

  • Lack of close follow-up such as that seen in a trial setting
  • Twice daily dosing
  • GI side effects
  • Multiple prescription use given the high comorbidity burden
  • Financial reasons

Similar studies of warfarin use, the authors report, “have shown that adherence improves with attendance at high-performing anticoagulation clinics. Consistent with this observation, individuals transitioned from warfarin had [higher odds] of being adherent to dabigatran compared to individuals started on dabigatran de novo. Thus, multi-modal interventions aiming at improving adherence to dabigatran may be beneficial and future studies should evaluate the effect of regular follow-up on dabigatran adherence.”

The results “suggest the advantages of dabigatran relative to warfarin in terms of laboratory monitoring and reduced interactions must be weighed against the implications of nonadherence on patient outcomes,” they conclude. “Further, these findings highlight the need for concerted efforts to bolster adherence to dabigatran to ensure optimal patient outcomes.”

Study Details

Mean patient age was 71.3 years and 98.3% were male. More than one-third of the population had congestive heart failure (38.3%) or diabetes (42.3%), while most had hypertension (88.1%) and 12% had prior stroke. Chronic kidney disease (12.5%), alcohol abuse (12.8%), liver disease (3.3%), and prior bleeding events (8.2%) were relatively uncommon.

 


Source:
Shore S, Carey EP, Turakhia MP, et al. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the Veterans Health Administration. Am Heart J. 2014;Epub ahead of print.

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Disclosures
  • Dr. Ho reports no relevant conflicts of interest.

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