Patient adherence to rivaroxaban in deep vein thrombosis, a cohort study in Switzerland: quantitative results

Abstract

Background Direct oral anticoagulants (DOACs) have the advantage of being administered orally at a fixed dose without laboratory monitoring, in contrast to the frequent international normalized ratio measurements used to adjust for vitamin K antagonists dosing. Rivaroxaban, has a short half-life. The anticoagulation effect rapidly decreases if medication adherence is suboptimal. Objective The purpose of this quantitative study (called RIVA) is to longitudinally describe adherence to rivaroxaban (implementation and persistence) in patients with deep vein thrombosis (DVT). Setting The community pharmacy of the Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland in collaboration with the angiology division of the Lausanne University Hospital (CHUV). Methods This is an observational study. Patients received rivaroxaban for 3 or 6 months: 15 mg twice a day during the first 3 weeks and then 20 mg once a day until the end of the treatment. Adherence was measured using electronic monitoring. Implementation and adherence were modelled using a generalized estimating equation model. Persistence was represented using a Kaplan-Meier survival curve. Main outcome measure Medication adherence (implementation and persistence). Results Thirty-one consecutive patients were included (68% male, mean age: 47 years old). The collected adherence data consisted of 57 inter-visit phases, 2899 electronic monitoring openings and a median follow-up of 92 days (IQR: 87; 100). Implementation to rivaroxaban was initially high [96.3 (92.8; 98.1)] but decreased during the first 3 weeks, until it reached 89.3 (76.0; 95.6). After the switch from twice a day 15 mg to a once a day 20 mg regimen, implementation increased again and remained stable [95.4 (92.2; 97.3)] for 90 days. Four patients who experienced adverse events discontinued the treatment before the end of the study and were considered non-persistent (clinically appropriate discontinuation). Conclusion Adherence to rivaroxaban in deep vein trombosis is high in persistent patients. Discontinuation is related to rivaroxaban adverse effects/toxicity. Implementation should be reinforced during the twice a day-phase, and this first 3-week experience should help patients and healthcare professionals choose the best timing for the once a day phase.

Estimation of adherence to medication treatment in presence of censoring

“…In patients having initiated a treatment, the study of the patient's medication behaviour is an assessment to be carried out over time, with interest in both the duration of individual persistence with treatment, and the quality of medication taking during the persistence period 1–11 . From a statistical point of view, we are faced with 2 different processes, interacting with each other: a binary variable with repeated measurements qualifying the daily dosing (correct/incorrect) during the individual follow‐up, and a continuous duration variable indicating the time until the drug is stopped, the latter being subject to censoring 12,13 …”

“…Oncology patient data at Unisanté, Lausanne up, and a continuous duration variable indicating the time until the drug is stopped, the latter being subject to censoring. 12,13 In this paper, we aimed to clarify the theoretical framework of such adherence analyses, indicating the assumptions that need to be made in order to estimate the desired quantities. Achieving unbiased estimates of medication persistence, implementation and adherence, besides being a general condition in statistics, also fulfils a requirement of the ESPACOMP Medication Adherence Reporting Guideline (EMERGE).…”

“…9 Classical survival analysis techniques, such as the Kaplan-Meier survival estimate, can be applied to estimate the distribution of the time to discontinuation in presence of censoring. [10][11][12] By contrast, implementation is a notion related to a binary outcome (correct/incorrect dosing) measured repeatedly over time (e.g. each day) until discontinuation of a patient.…”