Drospirenone-containing combined oral contraceptives and risk of venous thromboembolism

Date of Approval
Application Number
Lay Summary

Oral contraceptives, commonly referred to as “the pill”, are used to prevent unwanted pregnancies. Although they are a very effective method of birth control, they are known to cause blood clots called venous thromboembolism. The most recent generation of oral contraceptives contains the hormone drospirenone. These fourth generation oral contraceptives have been under particular scrutiny because of a potential increased risk of blood clots. However, previous studies examining this issue had important limitations. Given the large number of women taking these oral contraceptive pills, we need to better understand the risk of blood clots associated with their use. For this reason, we will perform a study that examines the risk of blood clots with drospirenone-containing combined oral contraceptives.

Technical Summary

Although several studies have examined the association between use of drospirenone-containing combined oral contraceptive (COCs) and the risk of venous thromboembolism (VTE), these studies had several important limitations, including confounding by history of oral contraceptive use, the use of inappropriate comparators, and outcome misclassification. Given the substantial number of women taking these contraceptives and the limitations of the existing literature, there remains a need for additional studies of this association. Using the CPRD, linked to Hospital Episode Statistics (HES; inpatient and outpatient), we will conduct a retrospective cohort study of all initiators of drospirenone- or levonorgestrel-containing COCs between May 1st, 2002 and March 31st, 2015. The date of the first drospirenone- or levonorgestrel-containing COCs prescription will define cohort entry. Initiators will be followed until incident VTE (defined by an inpatient diagnosis of VTE or outpatient diagnosis of VTE with either a prescription for anticoagulant therapy, INR testing, or death) or censoring due to discontinuation of use, switching to any other form of hormonal contraception, arterial thromboembolism (ATE), death, departure from the CPRD or HES, or the end of the study period (March 31st, 2015), whichever occurs first. Analyses will involve Cox proportional hazards models with high dimensional propensity scores.


Samy Suissa - Chief Investigator - McGill University
Kristian Filion - Corresponding Applicant - McGill University
Janie Coulombe - Collaborator - McGill University
Natasha Larivee - Collaborator - McGill University
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Vicky Tagalakis - Collaborator - McGill University


HES Admitted Patient Care;HES Outpatient