Oral anticoagulant persistence in patients with non-valvular atrial fibrillation: A cohort study using primary care data in Germany

PLoS One. 2017 Oct 10;12(10):e0185642. doi: 10.1371/journal.pone.0185642. eCollection 2017.

Abstract

This study examined characteristics and treatment persistence among patients prescribed oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). We identified 15,244 patients (51.8% male, 72.7% aged ≥70) with NVAF and no prior OAC therapy who were prescribed apixaban (n = 1,303), rivaroxaban (n = 5,742), dabigatran (n = 1,622) or vitamin-K antagonists (VKAs, n = 6,577) between 1-Dec-2012 and 31-Oct-2014 in German primary care (IMS® Disease Analyzer). We compared OAC persistence using Cox regression over patients' entire follow-up and using a data-driven time-partitioned approach (before/after 100 days) to handle non-proportional hazards. History of stroke risk factors (stroke/transient ischaemic attack [TIA] 15.2%; thromboembolism 14.1%; hypertension 84.3%) and high bleeding risk (HAS-BLED score≥3 68.4%) was common. Apixaban-prescribed patients had more frequent history of stroke/TIA (19.7%) and high bleeding risk (72.6%) than other OACs. 12-month persistence rates were: VKA 57.5% (95% confidence interval (CI) 56.0-59.0%), rivaroxaban 56.6% (54.9-58.2%), dabigatran 50.1% (47.2-53.1%), apixaban 62.9% (58.8-67.0%). Over entire follow-up, compared to VKA, non-persistence was similar with apixaban (adjusted hazard ratio 1.08, 95% CI 0.95-1.24) but higher with rivaroxaban (1.21, 1.14-1.29) and dabigatran (1.53, 1.40-1.68). Using post-hoc time-partitioned approach: in first 100 days, non-persistence was higher with apixaban (1.37, 1.17-1.59), rivaroxaban (1.41, 1.30-1.53) and dabigatran (1.91, 1.70-2.14) compared to VKA. Compared to apixaban, rivaroxaban non-persistence was similar (1.03, 0.89-1.20), dabigatran was higher (1.39, 1.17-1.66). After 100 days, apixaban non-persistence was lower than VKA (0.66, 0.52-0.85); rivaroxaban (0.97, 0.87-1.07) and dabigatran (1.10, 0.95-1.28) were similar to VKA. Furthermore, rivaroxaban (1.46, 1.13-1.88) and dabigatran (1.67, 1.26-2.19) non-persistence was higher than apixaban. This study describes real-world observations on OAC use, particularly early apixaban use following approval for NVAF, in Germany. We identified potential differential OAC prescribing and higher persistence with apixaban than other OACs after 100 days' treatment. Larger studies are needed with longer follow-up to establish long-term patterns.

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Cohort Studies
  • Dabigatran / therapeutic use*
  • Female
  • Germany
  • Hemorrhage / physiopathology
  • Humans
  • Hypertension / physiopathology
  • Ischemic Attack, Transient / physiopathology
  • Male
  • Primary Health Care
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • Risk Factors
  • Rivaroxaban / therapeutic use*
  • Stroke / prevention & control*
  • Thromboembolism / physiopathology
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • Vitamin K
  • apixaban
  • Rivaroxaban
  • Dabigatran

Grants and funding

This study was funded by Bristol-Myers Squibb, Paris, France (www.bmsfrance.fr) and Pfizer (www.pfizer.com). CL, DE, GH and GS were employed by Bristol-Myers Squibb at the time of the study and contributed to the study design, interpretation of results and manuscript. MJ, SC and AM were employed by OXON Epidemiology Ltd, which has received funding from Bristol-Myers Squibb to develop this study.