Fatal venous thromboembolism associated with different combined oral contraceptives: a study of incidences and potential biases in spontaneous reporting.
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.


CONCLUSIONS
Results from this study support a higher incidence of fatal VTE with desogestrel-containing COCs than with levonorgestrel-containing COCs.
Hedenmalm
Karin
K
Pharmacovigilance Unit and Clinical Trial Unit, Medical Products Agency, Uppsala, Sweden. karin.hedenmalm@mpa.se
Samuelsson
Eva
E
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D015982:Bias; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D012189:Retrospective Studies; D013923:Thromboembolism / Q000139:chemically induced* / Q000401:mortality; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000401:mortality
D003277:Contraceptives, Oral, Combined