Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial

Abstract

Introduction: Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring.

Objective: We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF).

Methods: Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks.

Results: In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3-89.7), 85.2% (95% CI 81.5-88.2), and 87.8% (95% CI 83.4-91.1). Serious adverse events were similar across groups.

Conclusion: High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits.

Clinical trial registration: This study is registered at ClinicalTrials.gov [NCT01884350].

Conflict of interest statement

GM reports research grants to his institution from ICAN, Fédération Française de Cardiologie, Medtronic, MSD, Pfizer, Sanofi-Aventis, Servier, and INSERM; consultancy fees from Beth Israel Deaconess Medical, Brigham Women’s Hospital, Menarini, TIMI Study Group, and ACTELION; and educational support from Cardiovascular Research Foundation, CME Resources, Europa, Elsevier, Lead-Up, WebMD CCC. CB, AD’A, and HD have received consultancy fees from Bristol-Myers Squibb/Pfizer. BC reports personal fees from St Jude Medical and research grants from Daiichi Sankyo. HJC and LD report research grants to their institutions from Bristol-Myers Squibb/Pfizer. FE has received speaker honoraria from Bristol-Myers Squibb. DAL reports research grants to her institution from Bristol-Myers Squibb and Boehringer Ingelheim, and speaker and consultancy fees from Boehringer Ingelheim, Bayer, and Bristol Myers Squibb/Pfizer. BB is a former employee of Bristol-Myers Squibb. AC is an employee of Pfizer Inc. EV reports grants to his institution from Boehringer and Sanofi; has received consultancy fees from Abbott, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, European Cardiovascular Research Center, Fresenius, LFB, Lilly, Medtronic, Pfizer, and Sorin Group, and has received lecture fees from Novartis.

Figures

Fig. 1

Study design. Patients consented to and initiated therapy with apixaban and were subsequently asked to participate in the implementation phase of the study. Following consent, patients were centrally randomized in a 1:1 ratio to receive standard-of-care patient information or an additional educational program. For subject discontinuations see Table 3 in the Electronic Supplementary Material. ASA acetylsalicylic acid, NVAF non-valvular atrial fibrillation, OAC oral anticoagulant, R randomization, SOC standard of care, VKA vitamin-K antagonist

Fig. 2

Implementation of the correct apixaban dose by study group at week 24 (mean; primary outcome). Implementation adherence (treatment taken as prescribed with one or less dose missed within 24 h and no tablet missed on the previous 2 consecutive days) was monitored by an electronic monitoring device. Not all patients handed in the device at week 24

Fig. 3

Overall implementation of the correct apixaban dose (mean) by study group. P > 0.7 for all between-group comparisons at 24 and 48 weeks. Apixaban with standard of care = patients randomized to receive only standard-of-care information following apixaban initiation; Apixaban with additional educational program = patients randomized to receive an additional educational program following apixaban initiation; Apixaban with secondary standard of care = patients with educational program switched to standard-of-care information only following 24 weeks of apixaban treatment. Additional data from all patients handing in the device at the end of the trial were included for calculating implementation adherence by week, up to week 48

Fig. 4

Persistence by study group over 48 weeks (secondary outcome). Apixaban with standard of care = patients randomized to receive only standard-of-care information following apixaban initiation; Apixaban with additional educational program = patients randomized to receive an additional educational program following apixaban initiation; Apixaban with secondary standard of care = patients with educational program switched to standard-of-care information only following 24 weeks of apixaban treatment