Risk of venous thromboembolism associated with chlormadinone acetate- and levonorgestrel-containing combined oral contraceptives - Insights from the retrospective RIVET-RCS study.

OBJECTIVE

We assessed the risk of venous thromboembolism (VTE) risk of chlormadinone acetate (CMA) 2 mg/ethinylestradiol (EE) 30 µg as opposed to levonorgestrel (LNG) 0.15 mg/EE 30 µg.

STUDY

DESIGN

We pooled data from four comparable, large, observational studies in a dataset comprising new users of combined oral contraceptives (COC). Individuals with a personal history of VTE were excluded. Incidence rates of confirmed VTE were summarized. Cox models were performed to calculate crude and adjusted hazard ratios (HRs).

RESULTS

We identified 31,379 COC users exposed to either CMA 2 mg/EE 30 µg or LNG 0.15 mg/EE 30 µg, contributing to 59,167 women-years. Sixty VTE were reported. VTE incidence rates were comparable between CMA- and LNG-cohorts (9.8/10,000 woman-years [WY]; 95% confidence interval [CI]: 6.36-14.50 vs. 10.38/10,000 WY; 95% CI: 7.23-14.44, respectively). The HR was 1.25 (95% CI: 0.72-2.14) after adjusting for age, BMI, family history of VTE and current duration of use.

CONCLUSION

Within the general limitations of observational research, we conclude that this study and its contributing studies provide a robust basis to compare the risk of VTE in users of CMA 2 mg/EE 30 µg to those of LNG 0.15 mg/EE 30 µg. While we found an HR > 1 for CMA 2 mg/EE 30 µg compared to LNG 0.15 mg/EE 30 µg, the increase was non-significant, and the absolute risk increase remained small and in line with previous studies.

IMPLICATIONS: No significant differences were found regarding the risk of VTE between users of CMA- and LNG-containing COCs. Incidence rates of VTE were in line with previous findings of VTE incidences across various COCs.