Family history of venous thromboembolism is a risk factor for venous thromboembolism in combined oral contraceptive users: A nationwide case-control study

Background: The aim was to assess the risk of venous thromboembolism (VTE) associated with use of combined oral contraceptives (COCs) in women with a family history of VTE. Methods: The study is a Swedish nationwide case-control study based on the Multigeneration register, the Swedish Hospital Discharge Register, the Outpatient Care Register, and the Swedish Prescribed Drug Register. Cases (n = 2,311) were non-pregnant Swedish women aged 15-49 with first VTE diagnoses between January 2006 and December 2010. Five controls without VTE were matched to each case on age and education level. Conditional logistic regression examined the associations with VTE with determination of odds ratio (OR) for first VTE diagnosis. Effect modification was assessed by interaction testing. Results: Both among controls (14.6 % vs. 4.5 %; p < 0.0001) and cases (27.2 % vs. 8.8 %; p < 0.0001) COC use was more common in women without a family history of VTE compared with women with a family history of VTE. In a multivariate conditional logistic regression model the OR for VTE was 2.53 (95 % CI 2.23-2.87) for COC users and 2.38 (2.09-2.71) for individuals with a family history of VTE. The OR for VTE for COC users with a family history of VTE was 6.02 (5.02-7.22). There was no significant interaction between family history of VTE and COC use (OR 0.92, 0.57-1.46). Conclusions: Family history of VTE is a risk factor for VTE in women using COCs. The low prevalence of COC use among women with a family history of VTE suggests that family history of VTE is considered when COCs are prescribed in Sweden. The present study may therefore even underestimate the importance of family history of VTE. The lack of interaction indicates that the risk of COC use in women with family history of VTE is determined by the product of the ORs for family history and COC use.