Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration

Abstract

Background: Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system.

Methods: We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques.

Results: Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction.

Conclusions: In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.

Figure 1

Pictorial representation of Proportion of Days covered calculation. Time periods labeled a, b, d, e and g represent time during which patient had dabigatran supply. Time period c represents duration of hospitalization and time period f represents duration following physician ordered prescription cancellation. Time period h represents total follow-up duration.

Figure 2

Cohort Creation. CHADS₂ score components include congestive heart failure (1 point), hypertension (1 point), age ≥75 years (1 point), diabetes mellitus (1 point), prior stroke (2 points), CHA₂DS₂VASc score components include congestive heart failure (1 point), hypertension (1 point), age ≥75 years (2 points), diabetes mellitus (1 point), prior stroke (2 points), vascular disease (1 point), age 65-74 years (1 point), female sex (1 point).

Figure 3

Distribution of Proportion of days covered across study cohort. x-axis displays proportion of days covered in increments of 10%, y-axis displays number of patients. Patients with PDC <80% were classified as non-adherent. Patients with PDC ≥80% were classified as adherent.