Innovative strategies to improve adherence to non-vitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation

This editorial refers to ‘Telemonitoring-based feedback improves adherence to non-vitamin K antagonist oral anticoagulants intake in patients with atrial fibrillation’†, by L. Desteghe et al., on page 1394. Stroke prevention is the principal priority in the management of patients with atrial fibrillation (AF), and oral anticoagulation is associated with a significant reduction in stroke/systemic embolism and all-cause mortality.1 However, central to this is medication adherence and persistence. The vitamin K antagonists (VKAs) have marked inter- and intrapatient variability in the international normalized ratio (INR) values, thus requiring regular anticoagulation monitoring to ensure a high time in therapeutic range (TTR). Indeed, poor TTR or anticoagulation cessation has been associated with worse outcomes,2 , 3 and the need for regular blood tests to check INRs provide an opportunity for healthcare professionals to monitor drug adherence and persistence. Education and counselling can also improve anticoagulation management,4 , 5 reinforced by smart technology, such as apps on smartphones. In a pilot trial (mAFA), the first prospective randomized trial of Mobile Health technology in patients with AF, the mAF app, integrating clinical decision support, education, and patient-involvement strategies, significantly improved knowledge, drug adherence, quality of life, and anticoagulation satisfaction.6 However, this approach suited patients in healthcare systems with high smartphone use, and the ability to utilize apps. This approach using apps may not be ideal for everyone. Indeed, Desteghe et al. 7 have previously reported that only a small proportion of their AF population seemed eligible for the Health Buddies app, although the latter was positively rated by its users, but many patients were not willing to participate in this study or to use the app. The main reasons for not participating were general lack of interest in participating in research or in the concept in particular (29%), not feeling comfortable using technology (22%), no interest by the grandchildren or their parents (20%), or too busy a lifestyle (12%). More recently, the availability of the non-VKA oral anticoagulants (NOACs) has changed the landscape of thromboprophylaxis.1 The NOACs do not require anticoagulation monitoring but, given that these drugs have a short half-life, it became apparent that efforts had to be directed towards improving patient adherence and persistence with treatment.8 The NOACs are generally better tolerated than VKAs, but patient engagement, education, and counselling are considered essential aspects of management to ensure optimal uptake, and adherence and different strategies may need to be utilized to suit different patients.9 In this issue of the journal, Desteghe et al. 10 report a randomized, single-blind, crossover, controlled trial in 48 AF patients on a once or twice daily (o.d. or b.i.d.) NOAC, to evaluate the effect of telemonitoring on adherence to NOAC. This study used a Medication Event Monitoring System which tracked NOAC intake during three phases of 3 months each, as follows: (i) daily telemonitoring; (ii) telemonitoring with immediate telephone feedback in case of intake errors; and (iii) an observation phase without daily transmissions. Persistence over the entire study was very high, at 98%. While telemonitoring-only led to very high taking and regimen adherence, the addition of direct feedback further improved adherence. Observation without daily monitoring resulted in a decline in NOAC adherence, although it was still high, at 94.3%. Of note, adherence was significantly higher for o.d. compared with b.i.d. NOAC regimes, although unprotected days were similar; nevertheless the small numbers preclude overinterpretation of this aspect. While feedback further optimized adherence, the cost-effectiveness analysis suggested that this had an incremental cost of €344 289 to prevent one stroke, which could be as low as €15 488 in high-risk patients with low adherence and optimized technology. The authors concluded that telemonitoring with or without feedback may be a cost-effective approach in high-risk patients deemed poorly adherent. Nevertheless, some limitations are apparent. There is a very small sample size, without a ‘no intervention group’ to see what ‘normal’ adherence is like. Also, the very fact that patients are in an adherence trial means they are self-selected (likely to be better adherers and/or to adhere better while being monitored). Finally, patients were not blinded to treatment allocation. This small study has implications for improving patient-centred approaches to optimize NOAC adherence, notwithstanding that patients could be highly selected, given the unusually high overall adherence rate, at 98%. There is also uncertainty whether all healthcare settings would have the facilities and personnel to undertake such telemonitoring and feedback, especially an ‘all-comers’ approach which could be expensive and not cost-effective. While this strategy could be cost-effective in some high-risk patient groups, the small numbers in the present study would need further prospective data in larger and more diverse cohorts to see if appropriate patient groups could be targeted for such interventions. What are the principles? The approaches to improve patient adherence could be summarized as ‘ADHERE ON’ (Take home figure). Assessment of the patient on the appropriateness of telemonitoring is needed, as this may not be suitable for everyone. The patient would need to be given the appropriate information and help in setting the management strategy. Education and counselling to explain the risks of non-adherence, as well as reinforcement of education is needed. Clearly observation and feedback is part of this, including direct observation or indirect methods including self-reporting, supplemented by family/caregivers, pill counts, mobile technologies, electronic medication monitors, etc. In short, patient engagement could ultimately improve drug adherence and persistence. This is essential with the NOACs, given their short half-life, as even missing a couple of doses would leave patients unprotected from stroke. What else can we do? Healthcare professionals have a key role. Collaboration between primary and secondary care can improve awareness and detection of AF, as well as streamlining stroke prevention pathways in a simple approach that leads to higher anticoagulation rates, translating to more strokes prevented and savings on healthcare costs.11 Ultimately, adherence to OAC for stroke prevention is only one part of the integrated care of AF patients that involves a holistic approach to AF management. This has been proposed as a Atrial fibrillation Better Care (ABC) pathway12, that involves Avoiding stroke (with anticoagulation), Better symptom management (and patient-centred, symptom-directed decisions on rate or rhythm control), and Cardiovascular and other risk factor management, including lifestyle and patient-centred approaches (Take home figure). Such a holistic and integrated simple approach to AF management would streamline decision-making and ultimately improve patient outcomes. Integrated approach to AF management. mHSM, mobile Health Services Management; VDOT, Video Directly Observed Therapy; MEMS, Medical Event Monitoring System; OAC, oral anticoagulants. Conflict of interest: G.Y.H.L. is a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally. D.A.L. has received investigator-initiated educational grants from Bristol Myers Squibb and Boehringer Ingelheim, and has been a speaker and consultant for Boehringer Ingelheim, Bayer, and Bristol Myers Squibb/Pfizer. T.S.P. is a speaker for Bayer.