Oral anticoagulant use in patients with AF

Oral anticoagulant prescription trends, profile use, and determinants of adherence in patients with atrial fibrillation

Perreault S, de Denus S, White-Guay B, Côté R, Schnitzer M, Dubé M et al. Pharmacotherapy. 2020 Jan;40(1):40-54. doi: 10.1002/phar.2350.

• DOAC usage has increased over time, from 22.1% in 2011 to 87.3% in 2017
• One year after oral anticoagulant initiation, persistence rates ranged from 53% with warfarin to 77% with high-dose apixaban
• Adherence to OACs remains a significant challenge in patients with AF

Atrial fibrillation (AF) is a cause of embolic stroke that is expected to become more prevalent in the coming years (Colilla et al., 2013). Additionally, ischemic strokes that are associated with AF are known to have a higher severity and mortality (McGrath et al., 2013).

With the introduction of direct oral anticoagulants (DOACs), warfarin is no longer the only oral anticoagulant (OAC) available for patients with AF. The limitations of warfarin, such as the need for routine monitoring with the international normalised ratio (INR), has led to widespread enthusiasm for the arrival of DOACs that directly target specific clotting factors with rapid onset of action and lower risk for drug interactions.

Previous research has also shown that DOACs effectively prevent ischemic events in patients with AF (January et al., 2014; Hart et al., 2007; Culebras et al., 2014; Lip et al., 2018).

However, while real-life data in patients with AF is important for understanding patient exposure, data on the uptake and pattern of use OACs remains limited.

In this database cohort study (2011 to 2017, N=33,311), the authors aimed to assess drug use, persistence rate, switching rate, adherence level, and predictors of adherence in patients receiving oral anticoagulants.

Assessing OAC use with a database cohort

The authors built the cohort from the Régie de l’Assurance Maladie du Quebec (RAMQ) and Med-Echo administrative databases consisting of new adult OAC AF patients within 1 year following hospitalisation.

A new user was defined as a patient who had never been exposed to DOACs or warfarin in the year before the cohort entry. Patients were then identified who filled a claim of warfarin or DOAC within the 1 year after hospital discharge. The DOACs included: dabigatran 100 or 150 mg twice daily, rivaroxaban 15 or 20mg per daily, and apixaban 2.5 or 5mg twice daily.

They then assessed trends of OAC use; persistence rate, defined as a gap between refills of no longer than two times the duration of the previous prescriptions; and adherence level, defined as the proportion of days covered (PDC) over a 1-year period following initiation.

A retrospective analysis

The usage of DOACs and warfarin has changed significantly from 2011–2017. Of the total OAC claims, the proportions of warfarin claims decreased from 77.9% in 2011 to 12.7% in 2017. By the end of 2017, DOACs accounted for 87.3% of claims, of which apixaban and rivaroxaban accounted for 60.1% and 23.4%, respectively.

Figure 1: Trends of new users of OACs from 2011 to 2017. DOAC, direct oral anticoagulant.

One year after the initiation of OAC:

• The highest rate of persistence was with a high 5 mg dose of apixaban (77%) and the lowest rate of persistence was warfarin (53%).
• Approximately 75% of incident OAC users were considered to be “adherent” (PDC ≥ 80%) with a PDC of 95.6 – 98.1%, compared with “nonadherent,” with a mean PDC between 43.1% and 50.7%.
• The proportion of patients who switched treatments was 12.6%, of these 16.4% switched from warfarin to DOACs and 9.6% switched from DOACs to another OAC.

Interestingly, high adherence levels were associated with older age, female sex, higher CHA2DS2-VASc score (to predict thromboembolic risk in AF), prior stroke, and treatment with chronic cardiovascular disease drugs.

These results were consistent with two previous large cohort studies in 2016 and 2017 that assessed warfarin and DOAC persistence rates in AF patients (Martinez et al., 2016; Mueller et al., 2017).

However, while general adherence to OAC therapy was good, this study found that 25% of new OAC users presented with a low adherence level. Improving adherence with OACs is therefore still a significant challenge to overcome in patients with AF.

The authors suggest that OAC type and dose, comorbidities, and co-medications may help to identify patients who are more likely to benefit from counselling regarding the importance of drug adherence.

References

Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112(8):1142–1147.

Culebras A, Messé SR, Chaturvedi S, Kase CS, Gronseth G. Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(8):716–724.

Hart RG, Pearce LA, Aguilar MI. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–867.

January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of cardiology/American heart association task force on practice guidelines and the heart rhythm society. Circulation. 2014;130(23):e199–e267.

Lip GYH, Banerjee A, Boriani G, Chiang C en, Fargo R, Freedman B, et al. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. 2018;154(5):1121–1201.

Martinez C, Katholing A, Wallenhorst C, Freedman SB. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC: A cohort study. Thromb Haemost. 2016;115(1):31–39.

McGrath ER, Kapral MK, Fang J, Eikelboom JW, O’Conghaile A, Canavan M, et al. Association of atrial fibrillation with mortality and disability after ischemic stroke. Neurology. 2013;81(9):825–832.

Mueller T, Alvarez-Madrazo S, Robertson C, Bennie M. Use of direct oral anticoagulants in patients with atrial fibrillation in Scotland: Applying a coherent framework to drug utilisation studies. Pharmacoepidemiol Drug Saf. 2017;26(11):1378–1386.