Risk of venous thromboembolism in users of oral contraceptives containing  drospirenone or levonorgestrel: nested case-control study based on UK General  Practice Research Database

Lianne Parkin; Katrina Sharples; Rohini K Hernandez; Susan S Jick

doi:10.1136/bmj.d2139

Contraception Oral Contraceptives

Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database

Parkin L, Sharples K, Hernandez RK, Jick SS

Published April 21, 2011 BMJ (Clinical Research Ed.), 342(apr21 2), d2139

DOI 10.1136/bmj.d2139 PMID 21511804 PMC PMC3081041

RRM Academy Synopsis

Drospirenone pills carried three times the clot risk of levonorgestrel

Among women aged 15 to 44 without major clot risk factors, current drospirenone pill users had about three times the odds of a non-fatal blood clot of levonorgestrel pill users, a UK nested case-control study found. The study matched 61 women with clots to 215 controls.

Key Findings

After adjusting for body mass index, drospirenone users had 3.3 times the odds of a first non-fatal clot with no other identified cause (95% confidence interval 1.4 to 7.6).
Seventeen of the 61 women with clots (28%) and 26 of the 215 matched controls (12%) were current users of the drospirenone pill.
The cohort held 318 825 women, and its incidence rate ratio, standardized for age, came to 2.7 (1.5 to 4.7).
Crude incidence per 100 000 woman years was 9.1 (6.6 to 12.2) with levonorgestrel and 23.0 (13.4 to 36.9) with drospirenone; ranges are 95% confidence intervals.
The odds ratio for pulmonary embolism alone was 2.1 (0.8 to 5.6). By age: 3.7 (1.3 to 10.7) under 35, 2.8 (0.7 to 10.7) at 35 or older; interaction P 0.7.

Interpretation

The study analyzed prescription and diagnosis records in the UK General Practice Research Database for women who started a new episode of combined pill use with either progestogen between May 2002 and September 2009. Women with major clot risk factors were excluded. The authors note that the small number of cases limited precision in the subgroups. They state that the overall risk remained low. They suggest that, for women wishing to take an oral contraceptive, prescribing levonorgestrel preparations as the first line choice would seem prudent.

RRM Context

Combined pills are suppressive medications that override ovulation. This paper measures a difference in clot risk between two of them in women without major clot risk factors. Restorative reproductive medicine looks for the cause of symptoms that a pill would otherwise cover.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel.

Design

Nested case-control study.

Setting

UK General Practice Research Database.

Participants

Women aged 15-44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009. Cases were women with a first diagnosis of venous thromboembolism; up to four controls, matched by age, duration of recorded information, and general practice, were randomly selected for each case.

Main Outcome Measures

Odds ratios and 95% confidence intervals estimated with conditional logistic regression; age adjusted incidence rate ratio estimated with Poisson regression.

Results

61 cases of idiopathic venous thromboembolism and 215 matched controls were identified. In the case-control analysis, current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use; the odds ratio adjusted for body mass index was 3.3 (95% confidence interval 1.4 to 7.6). Subanalyses suggested that referral, diagnostic, first time user, duration of use, and switching biases were unlikely explanations for this finding. The crude incidence rate was 23.0 (95% confidence interval 13.4 to 36.9) per 100,000 woman years in current users of drospirenone and 9.1 (6.6 to 12.2) per 100,000 woman years in current users of levonorgestrel oral contraceptives. The age adjusted incidence rate ratio was 2.7 (1.5 to 4.7).

Conclusions

These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.

Topics

Contraception › Oral Contraceptives › Metabolic Effects · Therapeutics › Prescribing Safety › Medication Safety in Pregnancy

Lianne Parkin, Katrina Sharples, Rohini K Hernandez, Susan S Jick

L Parkin, K Sharples, R Hernandez, Sue Jick, S Jick

PMID 21511804 21511804 DOI 10.1136/bmj.d2139 10.1136/bmj.d2139 Parkin et al. 2011, Parkin 2011

Keywords

Androstenes, Contraceptives, Oral, Contraceptives, Oral, Combined, Estrogens, Levonorgestrel, Drospirenone