Early real-world evidence of persistence on oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a cohort study in UK primary care.
OBJECTIVE
To examine the characteristics and persistence in patients newly initiated with oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF).


METHODS
Cohort study in Clinical Practice Research Datalink.


METHODS
UK primary care.


METHODS
15 242 patients with NVAF newly prescribed apixaban, rivaroxaban, dabigatran or vitamin K antagonists (VKAs) between 1 December 2012 and 31 October 2014. 13 089 patients were OAC naïve.


METHODS
Patient characteristics and risk of non-persistence compared to apixaban using Cox regression models over the entire follow-up and using a time-partitioned approach to handle non-proportional hazards.


RESULTS
Among the OAC naïve patients, VKAs were most common (78.1%, n=10 218), followed by rivaroxaban (12.1%, n=1589), dabigatran (5.7%, n=741) and apixaban (4.1%, n=541). High baseline stroke risk (CHA2DS2VASc ≥2) ranged from 80.2% (dabigatran) to 88.4% (apixaban and rivaroxaban). History of stroke and bleeding was the highest among apixaban (23.7% and 31.6%) and lowest among VKA patients (15.9% and 27.5%). Across the entire follow-up period, adjusting for differences in characteristics, there was no evidence of a difference in non-persistence between VKA and apixaban (HR 0.92 (95% CI 0.68 to 1.23)). Non-persistence was higher with dabigatran (HR 1.67 (1.20 to 2.32)) and rivaroxaban (HR 1.41 (1.02 to 1.93)) than apixaban. Using the partitioned approach, non-persistence was lower with VKA (HR 0.33 (0.22 to 0.48)), and higher with dabigatran (HR 1.65 (1.08 to 2.52)) compared to apixaban in the first 2 months of follow-up. After 2 months, non-persistence was higher with VKA (HR 1.70 (1.08 to 2.66)) and dabigatran (HR 2.10 (1.30 to 3.41)). Pooling OAC naïve and experienced patients, non-persistence was also higher with rivaroxaban compared to apixaban after 2 months of follow-up (HR 1.69 (1.19 to 2.39)).


CONCLUSIONS
Observed differential prescribing of OACs can result in channelling bias in comparative effectiveness research. Persistence patterns changed over follow-up time, but there are indications of improved persistence rates with apixaban over other OACs in the UK. A larger study with longer follow-up is needed to corroborate findings. This study is registered on ClinicalTrials.gov (NCT02488421).
OXON Epidemiology, London, UK.
Michelle E
ME
Johnson
Department of Worldwide Health Economics & Outcomes Research, Bristol-Myers Squibb, Paris, France.
Cinira
C
Lefèvre
OXON Epidemiology, London, UK.
Shuk-Li
SL
Collings
Department of Worldwide Health Economics & Outcomes Research, Bristol-Myers Squibb, Paris, France.
David
D
Evans
Pfizer, Berlin, Germany.
Sebastian
S
Kloss
Medical Department UK, Bristol-Myers Squibb, London, UK.
Essra
E
Ridha
OXON Epidemiology, London, UK.
Andrew
A
Maguire
atrial fibrillation; discontinuation patterns; oral anticoagulation
Am J Med. 2006 May;119(5):448.e1-19
16651058
J Am Coll Cardiol. 2014 May 27;63(20):2141-7
24657685
Europace. 2015 Jul;17(7):1007-17
26116685
Clin Appl Thromb Hemost. 2013 Nov-Dec;19(6):619-31
23698729
Stat Med. 1991 Apr;10(4):577-81
2057656
Circ Cardiovasc Qual Outcomes. 2013 Sep 1;6(5):567-74
23922182
J Clin Epidemiol. 2002 Apr;55(4):358-63
11927203
Rev Clin Esp. 2015 Mar;215(2):73-82
25288530
Heart. 2001 Sep;86(3):284-8
11514479
Circ Cardiovasc Qual Outcomes. 2010 Nov;3(6):624-31
20959565
Thromb Haemost. 2016 Jan;115(1):31-9
26246112
Clin Cardiol. 2014 Jan;37(1):32-47
24254991
Europace. 2016 Aug;18(8):1150-7
26830891
N Engl J Med. 2009 Sep 17;361(12):1139-51
19717844
Am Heart J. 2014 Oct;168(4):487-94
25262258
Am J Cardiol. 2012 Aug 1;110(3):453-60
22537354
Am J Med. 2002 Oct 1;113(5):359-64
12401529
Stroke. 2005 Jun;36(6):1115-9
15879330
Int J Epidemiol. 2015 Jun;44(3):827-36
26050254
Eur Heart J. 2012 Nov;33(21):2719-47
22922413
Br J Clin Pharmacol. 2010 Jan;69(1):4-14
20078607
Europace. 2015 Apr;17(4):530-8
25694537
Thromb Res. 2015 Aug;136(2):250-60
26073321
N Engl J Med. 2011 Sep 15;365(11):981-92
21870978
Heart. 2006 Aug;92 (8):1064-70
16387813
Eur J Clin Pharmacol. 2016 Mar;72 (3):329-38
26613954
Pharmacoepidemiol Drug Saf. 2005 Jul;14 (7):443-51
15898131