Clinical Study Synopsis

Transcription

1 Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. Healthcare Professionals should always refer to the specific labelling information approved for the patient's country or region. Data in this document or on the related website should not be considered as prescribing advice. The study listed may include approved and non-approved formulations or treatment regimens. Data may differ from published or presented data and are a reflection of the limited information provided here. The results from a single trial need to be considered in the context of the totality of the available clinical research results for a drug. The results from a single study may not reflect the overall results for a drug. The following information is the property of Bayer AG. Reproduction of all or part of this report is strictly prohibited without prior written permission from Bayer AG. Commercial use of the information is only possible with the written permission of the proprietor and is subject to a license fee. Please note that the General Conditions of Use and the Privacy Statement of bayer.com apply to the contents of this file.

2 08 Oct 2016 Study no Page: 1 of 4 Date of study report: 08 Oct 2016 Study title: Sponsor s study number: Registry study of adherence to treatment with rivaroxaban and warfarin in patients with atrial fibrillation, as requested by the Dental and Pharmaceutical Benefits Board (TLV) NCT number: Not Applicable EudraCT number: Not Applicable Sponsor: Bayer Clinical phase: IV Study objectives: The study objective is to describe and compare adherence among AF patients initiating treatment with rivaroxaban and warfarin, in response to a request of the Swedish reimbursement authority. Furthermore to describe and compare patient characteristics for the two treatment groups and to identify predictors of adherence. Test drug: Rivaroxaban (Xarelto, Bay ) Name of active Rivaroxaban ingredient(s): Dose: 15 mg and 20mg Route of Oral administration: Duration of treatment: Minimum 6 months Reference drug: Warfarin [Dose] Average dosing for AF patients is 1.8 tablets per day for male and 1.5 tablets for females. [Route of Oral administration] [Duration of treatment] Minimum 6 months Indication: Atrial fibrillation

3 08 Oct 2016 Study no Page: 2 of 4 A diagnosis of AF in the national Swedish Patient registry during inclusion Diagnosis and main period (3 October 2012 and 1 January 2015) and age 18 years. Patients criteria for inclusion: with valvular AF defined as mitralis stenosis or mechanical valvular replacement prosthesis were excluded. The following groups were studied: Rivaroxaban cohort: patients with rivaroxaban who had not used an oral anticoagulant within the previous 12 months ("OAC naive"). Date of first rivaroxaban purchase within the inclusion period defines index date. Warfarin cohort: patients with warfarin who had not used an oral anticoagulant within the previous 12 months ("OAC naive"). Date of first warfarin purchase within the inclusion period defines index date. The full AF cohort: all AF patients irrespective of treatment regime. Retrospective cohort study using national register linkage data. Study design: Methodology: Retrospective cohort study (including prescription, hospital in- and outpatient data, mortality and socioeconomic data). Data were retrieved from the following registers: The National Patient Register The National Dispensed Drug Register The LISA register (socioeconomic conditions, e.g. educational level and disposable income) The Causes of Death Register [Standard of reference] Warfarin Study center(s): Not Applicable, registry study Publication(s) based on the study (references): None at the time of the report creation Study period: Retrospective data from 03 Oct 2012 until 01 July 2015 Study Start Date: 01 OCT 2015 Study Completion Date: 13 NOV 2015 Early termination: Not Applicable Number of subjects: Planned: Analyzed: 57558

4 08 Oct 2016 Study no Page: 3 of 4 Criteria for evaluation Efficacy: Adherence to treatment with rivaroxaban and warfarin according to the drug at disposal principle. Adherence is defined as the ratio of number of days of treatment supply divided by the total length of follow-up time, and converted to a percentage. In addition adherence for the respective patient group treated with rivaroxaban or warfarin is calculated as the share of adherent patients defined as patients with access to rivaroxaban or warfarin to least >80% of time at risk. For rivaroxaban which has fixed daily dosages the prescribed dose per day is available from the Dispensed Drug register, the analysis will focus on the standard dosages/strengths for SPAF (i.e. 15mg and 20mg). For warfarin, which has no fixed dosing and consequently no prescribed daily dose from the Dispensed Drug Register, two complementary methods will be used to estimate the doses used on group level; the Auricula method (main analysis) and the Refill interval method. Safety: Not applicable. Description and Adherence was analyzed according to conditions valid at baseline; age and comparison of patient sex, socioeconomic conditions, previous and concomitant disease as well as characteristics and surgical procedures. identification of predictors of adherence: Statistical methods: For the description of differences between the cohorts at baseline, Chi2 analyses and t-tests were used. All tests were two-sided with p-values <0.05 considered as significant. Propensity score matching was used in order to reduce the likelihood of confounding by indication. Individual propensity scores for the likelihood of getting treatment with rivaroxaban rather than warfarin were obtained by logistic regression using all information about circumstances that could have influenced the choice as covariates. Pairwise 1:1 matching of patients treated with rivaroxaban and warfarin was then made on logit transformed propensity scores matched to the nearest neighbor with a caliper of 0.1. In this process patients with extremely high likelihood for either treatment are in effect excluded thus created two groups of equal size that are more similar in baseline characteristics than the original full cohort.

5 08 Oct 2016 Study no Page: 4 of 4 Substantial The study was conducted according to final Study Protocol from date 06 protocol changes: August 2015, and included no substantial amendments. Subject disposition and baseline 144,036 patients were identified who fulfilled the inclusion criteria of a diagnosis of atrial fibrillation in the national Patient Register. Of these 8,182 had filled a prescription of rivaroxaban on at least one occasion during the study period. After exclusions, two cohorts of previously OAC naïve patients were formed; one with new users of rivaroxaban (n=7,331) and one with new users of warfarin (n=51,086) which constitute the main study groups. Efficacy 84.6% of rivaroxaban patients, and 70.4% of warfarin patients were classified as compliant (p<0.001). After multivariable adjustment, treatment with rivaroxaban 20 mg o.d. was associated with 63% lower risk of non-compliance or interrupted treatment than with warfarin treatment (OR 0.37, 95% CI ). With rivaroxaban 15 mg o.d. the risk was 45% lower than with warfarin (OR 0.55, 95% CI ). Safety evaluation Not Applicable Description and comparison of patient characteristics and identification of predictors of adherence: Compared to warfarin treated patients, patients who had been prescribed rivaroxaban were slightly older (75.2 vs 74.5 years, p<0.001), more often female (46.2 vs. 43.0%, p<0.001), more often with university education (25.2 vs. 20.3%, p<0.001) and with an income on the highest quartile (29.9 vs. 26.5%, p<0.001). Overall, rivaroxaban and warfarin patients were at similar thromboembolic risk, as assessed by the CHA2DS2-VASc scheme (3.36 vs points, p=0.092), and the CHADS2 scheme (1.85 vs points, p=0.540). Rivaroxaban patients had slightly higher estimated baseline bleeding risk than warfarin patients as assessed by the HASBLED scheme (2.06 vs points, p<0.001). Patients with renal failure had less often been prescribed rivaroxaban than warfarin. Predictors for adherence were age over 65 years and for non-adherence end-stage renal disease, dementia, deep venous thrombosis, alcohol consumption, frequent falls and general drug compliance. Overall conclusions Use of rivaroxaban for stroke prophylaxis among patients with non-valvular atrial fibrillation was associated with higher compliance/endurance to treatment than among patients who had been given warfarin. Differences in background factors, or in general medicine compliance/endurance, could not explain this difference.

6 Appendix to Clinical Study Synopsis Product Identification Information Product Type US Brand/Trade Name(s) Brand/Trade Name(s) ex-us Generic Name Main Product Company Code Drug Xarelto Xarelto rivaroxaban BAY Other Company Code(s) Chemical Description Other Product Aliases IUPAC Name: 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4- morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2- thiophenecarboxamide Date of last Update/Change: 04 Mar 2013