Fatal Venous Thromboembolism Associated with Different Combined Oral Contraceptives: a Study of Incidences and Potential Biases in Spontaneous Reporting

Overview

Journal Drug Saf

Specialties Pharmacology
Toxicology

Date 2005 Sep 27

PMID 16180940

Citations 1

Authors

Karin Hedenmalm

Eva Samuelsson

Affiliations

Soon will be listed here.

Abstract

Background: Fatal venous thromboembolism (VTE) is a rare complication of combined oral contraceptive (COC) treatment. This study aims to determine incidences of fatal VTE in relation to the type of COC and the percentage of cases reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC). A further aim is to compare the characteristics of reported and not reported cases.

Methods: This retrospective study is a separate analysis using data from a larger study that included women aged 15-44 years between 1990 and 1999 with VTE coded as the underlying or contributory cause of death in the Swedish Cause of Death Register. COC use within 2 months of the date of symptom onset or death was identified in 28 cases. Sales data were obtained from the National Corporation of Swedish Pharmacies. Reported cases were identified in the SADRAC database.

Results: After excluding two cases where the type of COC was unknown, the crude incidences of fatal VTE were 5.1 (95% CI 2.3, 9.6), 8.6 (95% CI 4.3, 15.4) and 9.1 (95% CI 3.3, 19.8) cases per million women per year for levonorgestrel-, desogestrel- and norethisterone-containing COCs, respectively. Age-adjusted incidences were approximately twice as high for desogestrel- and norethisterone-containing COCs compared with levonorgestrel-containing COCs, although differences were not statistically significant. Thirty-six percent of cases were reported. Reporting was positively associated with information in medical records relevant to the VTE diagnosis that the patient was a COC user and was significantly higher in northern Sweden.

Conclusion: Results from this study support a higher incidence of fatal VTE with desogestrel-containing COCs than with levonorgestrel-containing COCs.

Citing Articles

Combined oral contraceptives: venous thrombosis.

de Bastos M, Stegeman B, Rosendaal F, van Hylckama Vlieg A, Helmerhorst F, Stijnen T Cochrane Database Syst Rev. 2014; (3):CD010813.

PMID: 24590565 PMC: 10637279. DOI: 10.1002/14651858.CD010813.pub2.

References

Farmer R, Lawrenson R, Thompson C, Kennedy J, Hambleton I . Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet. 1997; 349(9045):83-8. DOI: 10.1016/s0140-6736(96)07496-x. View

Rosendaal F . Venous thrombosis: a multicausal disease. Lancet. 1999; 353(9159):1167-73. DOI: 10.1016/s0140-6736(98)10266-0. View

. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995; 346(8990):1575-82. View

. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995; 346(8990):1582-8. View

Jick H, Kaye J, Vasilakis-Scaramozza C, Jick S . Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis. BMJ. 2000; 321(7270):1190-5. PMC: 27524. DOI: 10.1136/bmj.321.7270.1190. View

Odlind V, Milsom I, Persson I, Victor A . Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills?. Acta Obstet Gynecol Scand. 2002; 81(6):482-90. View

Moride Y, Haramburu F, Requejo A, Begaud B . Under-reporting of adverse drug reactions in general practice. Br J Clin Pharmacol. 1997; 43(2):177-81. PMC: 2042725. DOI: 10.1046/j.1365-2125.1997.05417.x. View

Tosetto A, Frezzato M, Rodeghiero F . Prevalence and risk factors of non-fatal venous thromboembolism in the active population of the VITA Project. J Thromb Haemost. 2003; 1(8):1724-9. DOI: 10.1046/j.1538-7836.2003.00313.x. View

Farmer R, Lawrenson R, Todd J, Williams T, MacRae K, Tyrer F . A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives. Br J Clin Pharmacol. 2000; 49(6):580-90. PMC: 2015039. DOI: 10.1046/j.1365-2125.2000.00198.x. View

10.

Skjeldestad F, Amundsen T, Hoibraaten E . [Reporting of adverse drug reactions to the Norwegian Drug Control Agency]. Tidsskr Nor Laegeforen. 2000; 120(3):336-8. View

11.

Samuelsson E, Hedenmalm K, Persson I . Mortality from venous thromboembolism in young Swedish women and its relation to pregnancy and use of oral contraceptives--an approach to specifying rates. Eur J Epidemiol. 2005; 20(6):509-16. DOI: 10.1007/s10654-005-4266-7. View

12.

Carvajal A, Begaud B, Moride Y, Vega T, Arias L . Under-reporting of adverse drug reactions. Estimate based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharmacol. 1998; 54(6):483-8. DOI: 10.1007/s002280050498. View

13.

Jick H, Jick S, Gurewich V, Myers M, Vasilakis C . Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet. 1995; 346(8990):1589-93. DOI: 10.1016/s0140-6736(95)91928-7. View

14.

Parkin L, Skegg D, Wilson M, Herbison G, Paul C . Oral contraceptives and fatal pulmonary embolism. Lancet. 2000; 355(9221):2133-4. DOI: 10.1016/S0140-6736(00)02382-5. View

15.

Backstrom M, Mjorndal T, Dahlqvist R . Attitudes to reporting adverse drug reactions in northern Sweden. Eur J Clin Pharmacol. 2001; 56(9-10):729-32. DOI: 10.1007/s002280000202. View

16.

Backstrom M, Dahlqvist R, Mjorndal T, Spigset O, Hedenmalm K, Granberg K . [A regional center for reporting adverse drug reactions in Umeå. Prompt handling results in quick feedback]. Lakartidningen. 1995; 92(3):148-50. View

17.

Belton K . Attitude survey of adverse drug-reaction reporting by health care professionals across the European Union. The European Pharmacovigilance Research Group. Eur J Clin Pharmacol. 1997; 52(6):423-7. DOI: 10.1007/s002280050314. View

18.

Nightingale A, Lawrenson R, Simpson E, Williams T, MacRae K, Farmer R . The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contracept Reprod Health Care. 2001; 5(4):265-74. DOI: 10.1080/13625180008500402. View

19.

Ekbom Y, Hedenmalm K, Dalin L, Lonnroth K, Persson I . [Reporting of side-effects--a system in need of improvement. Reporting of a physician questionnaire]. Lakartidningen. 2002; 99(34):3290-5. View

20.

Samuelsson E, Hagg S, Backstrom M, Granberg K, Mjorndal T . [Thrombosis caused by oracl contraceptives. Underreporting to the adverse effects registry]. Lakartidningen. 1996; 93(37):3117-8, 3121-4. View