Time-trends in adherence to NOAC treatment in AF patients newly treated from 2012 to 2015 and impact of adherence on stroke incidence and competitive mortality in France

Background Very few epidemiological data focused on the impact of non-adherence on survival and stroke incidence in France. Purpose The objective of this study was to describe time-trends adherence to NOAC from 2012 to 2015, and to estimate the impact of non-adherence to NOAC on stroke incidence and mortality as a competing cause. Methods All AF patients > 20 years old, residing in France, and newly treated by NOAC between 2012 and 2015 were included using the nationwide SNDS database. Patients were followed for 2 calendar years or till the first occurrence of one of the following events: death, switch to a VKA, hospitalisation for stroke, any systemic embolism, or hemorrhages. Adherence to NOAC treatment was estimated by the proportion of days covered (PDC) by the treatment. We used a Fine and Gray regression model to estimate sub-distribution hazard ratio (SHR) for stroke and Cox regression models to compute cause-specific hazard ratios (CSHR) death. Results In 2015, 123,540 patients were estimated newly treated by NOAC for AF indication versus 54,129 in 2012. The median follow-up was 2 years. Proportion of patients with PDC > 80% increased between 2012 and 2015, from 59.1% to 65.0%. Among treated patients, the proportion of days covered by standard dosage increased from 33.2% to 59.2%. Adherent patients were older, were more often women, had more frequently history of stroke, heart failure, treated hypertension and diabetes, compared with non-adherent patients. In multivariate analysis, non-adherence to NOAC treatment was associated with 14% increase in stroke occurrence and 23% increase in death. Conclusion Adherence to NOAC increased between 2012 and 2015 with a higher proportion of patients treated with standard doses, and less patients treated with reduced or out-of-recommendation dosage. Non-adherence to NOAC was associated with important increased risk of stroke and death highlighting the crucial need improve patients’ adherence to NOAC.