Natasha Larivée1,2, Samy Suissa1,2,3, Janie Coulombe1, Vicky Tagalakis1,4, Kristian B Filion5,6,7. 1. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada. 2. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. 3. Department of Medicine, McGill University, Montreal, QC, Canada. 4. Division of General Internal Medicine, Jewish General Hospital, Montreal, QC, Canada. 5. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste Catherine, Montreal, QC, H3T 1E2, Canada. kristian.filion@mcgill.ca. 6. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. kristian.filion@mcgill.ca. 7. Department of Medicine, McGill University, Montreal, QC, Canada. kristian.filion@mcgill.ca.
Abstract
INTRODUCTION: The effects of drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) remain controversial due to the challenge in distinguishing between first-time users and restarters, and their different underlying VTE risks, in healthcare databases. OBJECTIVES: The aim of this study was to describe the challenge of studying the risk of VTE among first-time users of drospirenone-containing COCs in a healthcare database and assess the risk among first-time users and restarters. METHODS: We used data from the Clinical Practice Research Datalink to construct two cohorts. The first-time user cohort included all women aged 16-45 years who received a first ever prescription of drospirenone- or levonorgestrel-containing COCs between May 2002 and March 2015. The restarter cohort included those who were restarting a COC after a period of non-use of ≥6 months. Cox proportional hazards models adjusted for high dimensional propensity scores were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The final cohorts included 55,139 first-time users (3582 drospirenone and 51,557 levonorgestrel) and 162,959 restarters (23,191 drospirenone and 139,768 levonorgestrel). The adjusted HR of VTE associated with drospirenone versus levonorgestrel was 3.19 (95% CI 1.12-9.08) for first-time users and 1.96 (95% CI 1.12-3.41) for restarters. CONCLUSIONS: We found an elevated risk of VTE associated with drospirenone-containing COCs in comparison with levonorgestrel-containing COCs in both cohorts. While left truncation of healthcare databases is a concern for the identification of first-time users, the use of a more explicit cohort of restarters suggests a doubling of VTE risk with drospirenone-containing COCs.
INTRODUCTION: The effects of drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) remain controversial due to the challenge in distinguishing between first-time users and restarters, and their different underlying VTE risks, in healthcare databases. OBJECTIVES: The aim of this study was to describe the challenge of studying the risk of VTE among first-time users of drospirenone-containing COCs in a healthcare database and assess the risk among first-time users and restarters. METHODS: We used data from the Clinical Practice Research Datalink to construct two cohorts. The first-time user cohort included all women aged 16-45 years who received a first ever prescription of drospirenone- or levonorgestrel-containing COCs between May 2002 and March 2015. The restarter cohort included those who were restarting a COC after a period of non-use of ≥6 months. Cox proportional hazards models adjusted for high dimensional propensity scores were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The final cohorts included 55,139 first-time users (3582 drospirenone and 51,557 levonorgestrel) and 162,959 restarters (23,191 drospirenone and 139,768 levonorgestrel). The adjusted HR of VTE associated with drospirenone versus levonorgestrel was 3.19 (95% CI 1.12-9.08) for first-time users and 1.96 (95% CI 1.12-3.41) for restarters. CONCLUSIONS: We found an elevated risk of VTE associated with drospirenone-containing COCs in comparison with levonorgestrel-containing COCs in both cohorts. While left truncation of healthcare databases is a concern for the identification of first-time users, the use of a more explicit cohort of restarters suggests a doubling of VTE risk with drospirenone-containing COCs.
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Authors: Sinéad M Langan; Sigrún Aj Schmidt; Kevin Wing; Vera Ehrenstein; Stuart G Nicholls; Kristian B Filion; Olaf Klungel; Irene Petersen; Henrik T Sorensen; William G Dixon; Astrid Guttmann; Katie Harron; Lars G Hemkens; David Moher; Sebastian Schneeweiss; Liam Smeeth; Miriam Sturkenboom; Erik von Elm; Shirley V Wang; Eric I Benchimol Journal: BMJ Date: 2018-11-14
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