Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users.
BACKGROUND
Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing transdermal patch (NGMN) and the etonogestrel vaginal ring (ETON)] may place women at even higher risk of thrombosis than other older low-dose CHCs with a known safety profile.


METHODS
All VTEs and all hospitalized ATEs were identified in women, ages 10-55 years, from two integrated health care programs and two state Medicaid programs during the time period covering their new use of DRSP, NGMN, ETON or one of four low-dose estrogen comparator CHCs. The relative risk of thrombotic and thromboembolic outcomes associated with the newer CHCs in relation to the comparators was assessed with Cox proportional hazards regression models adjusting for age, site and year of entry into the study.


RESULTS
The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33-2.35) for VTE and 2.01 (1.06-3.81) for ATE. The increased risk of DRSP was limited to the 10-34-year age group for VTE and the 35-55-year group for ATE. Use of the NGMN patch and ETON vaginal ring was not associated with increased risk of either thromboembolic or thrombotic outcomes.


CONCLUSIONS
In new users, DRSP was associated with higher risk of thrombotic events (VTE and ATE) relative to low-dose estrogen comparator CHCs, while the use of the NGMN patch and ETON vaginal ring was not.
Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA. steve.sidney@kp.org
Stephen
S
Sidney
T Craig
TC
Cheetham
Frederick A
FA
Connell
Rita
R
Ouellet-Hellstrom
David J
DJ
Graham
Daniel
D
Davis
Michael
M
Sorel
Charles P
CP
Quesenberry
William O
WO
Cooper
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000009:adverse effects*; D001158:Arteries; D002140:California / Q000453:epidemiology; D002648:Child; D003271:Contraceptive Agents, Female / Q000009:adverse effects*; D017135:Desogestrel / Q000009:adverse effects*; D004338:Drug Combinations; D004967:Estrogens / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D009644:Norgestrel / Q000009:adverse effects / Q000031:analogs & derivatives*; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology; D013714:Tennessee / Q000453:epidemiology; D013923:Thromboembolism / Q000139:chemically induced / Q000453:epidemiology; D013997:Time Factors; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000453:epidemiology*; D014861:Washington / Q000453:epidemiology; D055815:Young Adult
D000736:Androstenes; D003271:Contraceptive Agents, Female; D004338:Drug Combinations; D004967:Estrogens; C511292:Ortho Evra; C534342:drospirenone and ethinyl estradiol combination; C044815:etonogestrel; D009644:Norgestrel; D004997:Ethinyl Estradiol; D017135:Desogestrel