Oral Contraceptives in Patients Who have Experienced One Venous Thrombosis

A systematic review 1 including 8 case-control studies, 6 follow-up studies and one randomised trial was abstracted in DARE. The unweighted summary relative risk for a new venous thrombosis or thromboembolism (VTE) was 2.9 (95% CI 0.5 to 17)(G test for homogeneity p<0.001). For case-control studies the RR was 4.2 (95% CI 1.3 to 14), and for follow-up studies it was 2.1 (95% CI 0.3 to 16). For the one RCT it was 1.1 (95% CI 0.4 to 2.9). The funnel plot did not reveal evidence of publication bias.

In a prospective cohort study 2 in France the risk of a recurrent VTE in women after a first oestrogen contraception associated VTE episode was assessed. Women under 50 years were consecutively enrolled between 1992 and 2011. Of the 241 women who were followed-up after stopping anticoagulation, there were 180 COC-users and 61 non-users. Median duration of follow-up off-anticoagulants was 66 months (interquartile range: 33-103). There were 14 recurrences in COC-users and 5 cases in non-users. No significant association was found between exposure to COC and the incidence of recurrent VTE after adjustment for age or after restricting the analysis to major unprovoked VTE: incidence rate of recurrence 17.9/1,000/year (95% CI: 9.6-33.2) in women with COC as compared with 17.6/1,000/year (95% CI: 6.6-47) with an incidence ratio of 0.7 (95% CI: 0.2-2.4, p=0.59).

A meta-analysis 3 assessed the thrombosis risk in thrombophilic COC-users. 12 case-control and 3 cohort studies were included. A distinction was made between 'mild' (factor V Leiden and prothrombin-G20210A mutation) and 'severe' thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, double heterozygosity or homozygosity of factor V Leiden and prothrombin-G20210A mutation). In COC-users, mild thrombophilia increased the risk of VTE almost 6-fold (rate ratio [RR], 5.89; 95%CI 4.21 to 8.23) and severe 7-fold (RR, 7.15; 95% CI, 2.93 to 17.45). The cohort studies showed that absolute VTE risk was far higher in COC-users with severe thrombophilia than in those with mild thrombophilia (4.3 to 4.6 vs. 0.49 to 2.0 per 100 pill-years, respectively), and these differences in absolute risks were also noted in non-affected women (0.48 to 0.7 vs. 0.19 to 0.0), but with the caveat that absolute risks were estimated in relatives of thrombophilic patients with VTE (i.e. with a positive family history). The investigators concluded that the additive VTE risk of mild thrombophilia is modest.

References

• Koster T, Small RA, Rosendaal FR, Helmerhorst FM. Oral contraceptives and venous thromboembolism: a quantitative discussion of the uncertainties. J Intern Med 1995 Jul;238(1):31-7. [PubMed][DARE]
• Le Moigne E, Delluc A, Tromeur C et al. Risk of recurrent venous thromboembolism among young women after a first event while exposed to combined oral contraception versus not exposed to: a cohort study. Thromb Res 2013;132(1):51-5. [PubMed]
• van Vlijmen EF, Wiewel-Verschueren S, Monster TB et al. Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2016;14(7):1393-403. [PubMed]