CHANGES OVER TIME IN TREATMENT PERSISTENCE OF ORAL ANTICOAGULANTS IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

Abstract Background A recent systematic review highlighted significant gaps in the evidence on atrial fibrillation (AF) patients' adherence to oral anticoagulants (OAC). Current evidence suffers from short follow-up times, focuses on the first OAC and does not take switching into account. There is also lack of observational data on adherence to warfarin due to its varying dose that complicates the calculations. As such there is lack of evidence on comparative adherence between VKAs and DOACs and whether the convenience of DOACs translates into better adherence in AF patients. Purpose Our objective was to measure AF patients' long-term OAC adherence and compare the impact of taking direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) on adherence, while accounting for switching. Methods Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996–2019), incident adult cases of AF were identified. The primary measure of adherence was proportion of days covered (PDC). Consecutive rolling 90-day windows were created for each patient starting from their first OAC prescription fill date until the end of their follow-up. The PDC for each 90-day rolling window was calculated and averaged to yield mean adherence over the follow-up period for each patient. Permanent medication discontinuation resulted in a PDC of 0 for all subsequent rolling windows after their supply ran out. As such, both poor execution and non-persistence were measured simultaneously. The association between drug class and adherence was assessed using generalized mixed effect linear regression models with drug class treated as time-varying covariate to account for switching. Results The study cohort was 30,264 AF patients [mean age 72.2 years (SD11.0), 44.6% female, mean CHA2DS2-VASc 2.94 (SD1.4)] with mean follow-up of 7.7 (SD 4.8) years. The mean PDC was 0.71 (SD 0.27) with 51% of the cohort having mean PDC values below the conventional threshold of adherence (PDC<0.8). Adherence dropped over time with the greatest decline in the first two years after therapy initiation. After controlling for all other confounders and accounting for switching, taking VKA compared to DOAC was, on average, associated with a 1-day decrease in number of days of medication-taking per year. Conclusion AF patients' OAC adherence was below the conventional threshold of 0.8, and dropped over time, particularly in the first two years. Drug class had no clinically meaningful impact on medication adherence. Our study highlights the need for effective adherence interventions particularly early in OAC therapy. Our findings also emphasizes that prescribers should not assume inherently better adherence for DOACs and should instead choose OAC in conversation with the patient and in accordance with their values and preferences. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research grant

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COMPARISON OF TREATMENT PERSISTENCE IN THE REAL-WORLD USE OF NOVEL ORAL ANTICOAGULANTS AMONG PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)30793-8 ◽

2016 ◽

Vol 67 (13) ◽

pp. 792 ◽

Cited By ~ 1

Author(s):

Cinira Lefevre ◽

Michelle Johnson ◽

Shuk-Li Collings ◽

David Evans ◽

Sebastian Kloss ◽

...

Keyword(s):

Atrial Fibrillation ◽

Real World ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

Treatment Persistence ◽

The Real

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Shifting from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: predictors, patterns and temporal trends

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02295-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Arthur Shiyovich ◽

Varda Shalev ◽

Gabriel Chodick ◽

Matanya Tirosh ◽

Amos Katz ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Temporal Trends ◽

Female Gender ◽

Healthcare Services ◽

Vitamin K Antagonist ◽

Incident Cases ◽

Over Time

Abstract Background Non-Vitamin K antagonist oral anticoagulants (NOACs) emerged as an alternative with comparable or superior efficacy and safety to vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). Objectives The aim of the current study was to investigate the patterns, predictors, timelines and temporal trends of shifting from VKAs to NOACs. Methods In this retrospective observational study, the computerized database of a large healthcare provider in Israel, Maccabi Healthcare Services, was searched to identify patients with AF for whom either a VKA or NOAC was prescribed between 2012 and 2015. Time from diagnosis to therapy initiation and to shifting between therapies was evaluated. Results Out of 6987 eligible AF incident patients, 2338 (33.4%) initiated treatment with a VKA and 2221 (31.7%) with a NOAC. In addition, 5259 prevalent patients were analyzed. During the study period, NOAC prescriptions proportion among the newly diagnosed cases increased from 32 to 68.4% (p for trend < 0.001). The median time from diagnosis to first dispensing was greater in NOAC than VKA and decreased among patients treated with NOAC during the study period (2012: 1.9 and 0.3 months, 2015: 0.7 and 0.2 months, respectively). During follow-up, 3737 (49%) patients (54.3% and 47.1% of the incident and prevalent cases, respectively), shifted from a VKA to a NOAC, after a median of 22 months and 39 months in the incident and prevalent cases, respectively, decreasing throughout the study period. Female gender, younger age, southern district, higher CHADS2 and CHA2DS2-VASC score, non-smoking, and treatment with antiplatelets were associated with a greater likelihood for therapy shift. Shifting from a NOAC to a VKA decreased over time from 8 to 4.5% in 2012 to 0.5% and 0.7% in 2015 in the incident and prevalent groups, p < 0.001 respectively. Conclusions Shifting from VKA to NOAC occurred in 50% of the cases, more frequently among incident cases, and younger patients with greater stroke risk. Shifting from a NOAC to a VKA was much less frequent, yet it occurred more often in incident cases and decreased over time. A socially and economically sensitive program to optimize the initiation of OAC therapy upon diagnosis is warranted.

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P4783Treatment persistence of patients with atrial fibrillation on VKA or NOAC: Data from GLORIA-AF Phase III 1-year interim analysis

European Heart Journal ◽

10.1093/eurheartj/ehz745.1159 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

G Y H Lip ◽

H.-C Diener ◽

S J Dubner ◽

J L Halperin ◽

K J Rothman ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Interim Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Phase Iii ◽

Treatment Persistence ◽

Geographical Regions ◽

Dosing Regimens ◽

The Impact

Abstract Background Oral anticoagulation (OAC) persistence is important for optimizing stroke prevention in patients with atrial fibrillation (AF); non-vitamin K oral anticoagulants (NOACs) generally show better persistence than vitamin K antagonists (VKAs), while the impact of dosing regimens remains unclear. We compared treatment persistence of NOACs and VKAs, and of NOAC dosing regimens in the prospective GLORIA-AF registry program. Methods Patients newly diagnosed with AF were enrolled in Phase III of GLORIA-AF (2014–2016) from 4 geographical regions (North America [NA], Europe, Asia and Latin America). Treatment persistence after 1 year for i) NOAC (dabigatran, rivaroxaban, apixaban, edoxaban) vs VKA, and ii) twice daily (bid, dabigatran, apixaban) vs once daily (od; rivaroxaban, edoxaban) NOAC treatment was analysed using multivariable Cox analysis; propensity score trimming was used to reduce bias due to unmeasured confounders. Missing data was handled by multiple imputation. Results Overall, 21,592 patients were enrolled (4970 [23%] patients on VKAs, 12,797 [59%] on NOACs, 2391 [11%] on antiplatelets, and 1426 [6.6%] received no therapy; 8 [0.04%] received other treatment). After trimming, 11,935 and 4484 patients treated with NOACs and VKAs, respectively, were compared. NOACs had better treatment persistence than VKAs (discontinuation hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.69–0.81). Other relevant associations were decreased OAC persistence for symptomatic AF, NA and Asia regions (Table). There was no difference in treatment persistence for patients on a bid (N=7842) vs od (N=4098) NOAC (discontinuation HR=0.94, 95% CI 0.86–1.02). Conclusion In this 1-year interim analysis of GLORIA-AF Phase III, treatment persistence was improved with NOACs vs VKAs, whereas for NOACs, dosing regimen (bid vs od) had no impact on treatment persistence. Acknowledgement/Funding The GLORIA-AF Registry program was funded by Boehringer-Ingelheim

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Decline in renal function and oral anticoagulation dose reduction among patients with atrial fibrillation

Heart ◽

10.1136/heartjnl-2019-315792 ◽

2020 ◽

Vol 106 (5) ◽

pp. 358-364 ◽

Cited By ~ 6

Author(s):

Taku Inohara ◽

DaJuanicia N Holmes ◽

Karen Pieper ◽

Rosalia G Blanco ◽

Larry A Allen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Dose Reduction ◽

Oral Anticoagulation ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

The Us ◽

Informed Treatment ◽

Over Time

ObjectiveNon-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline.MethodsWe included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing.ResultsAmong 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of −6.63 mL/min for NOACs and −6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year.ConclusionsIn the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction.

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