Abstract
Objectives
The “International Active Surveillance Study of Women Taking Oral Contraceptives”
investigated the risks of short- and long-term use of an extended 24-day regimen of
drospirenone and ethinylestradiol (DRSP24d) compared to established oral contraceptives (OCs) in a routine clinical setting.
Study Design
Prospective, controlled, noninterventional cohort study conducted in the United States
and six European countries with three main cohorts: new users of DRSP24d, DRSP21d (21-day regimens of DRSP-containing OCs), and non-DRSP (OCs without DRSP). All self-reported
clinical outcomes of interest (OoI) were validated via attending physicians and relevant
source documents. Main OoI were serious clinical outcomes, in particular venous thromboembolism
(VTE). Comprehensive follow-up procedures were implemented. Statistical analyses were
based on Cox regression models. Primary statistical variable was the VTE hazard ratio
(HR) for DRSP24d vs. non-DRSP.
Results
A total of 2285 study centers enrolled 85,109 women. Study participants were followed
for 2 to 6 years, which generated 206,296 woman-years (WY) of observation. A low loss
to follow-up of 3.3% was achieved. DRSP24d, DRSP21d, non-DRSP and levonorgestrel-containing OCs (LNG) showed similar incidence rates
of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression
and other serious adverse events. VTE incidence rates for DRSP24d, DRSP21d, non-DRSP and LNG were 7.2, 9.4, 9.6 and 9.8 VTE/10,000 WY, respectively. Adjusted
HRs for DRSP24d vs. non-DRSP and DRSP24d vs. LNG were 0.8 [95% confidence interval (CI), 0.5–1.3] and 0.8 (95% CI, 0.4–1.5).
Conclusion
DRSP24d, DRSP21d, non-DRSP and LNG use was associated with similar risks of serious adverse events,
and particularly VTE, during routine clinical use.
Implication Statement
The 24-day regimen of drospirenone-containing combined OCs is associated with similar
risks of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression
and other serious adverse events compared to 21-day regimens of drospirenone-containing
combined OCs, OCs without drospirenone and LNGs.
Keywords
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Article info
Publication history
Published online: February 06, 2014
Accepted:
January 28,
2014
Received in revised form:
January 27,
2014
Received:
December 4,
2013
Footnotes
☆Conflict of interest: The study was funded by a manufacturer of hormonal contraceptives. The study was supervised by an independent Safety Monitoring and Advisory Council with full authority over the study (including study protocol, protocol amendments, data analysis and stopping the study). The funder had no access to the source data and did not participate in designing the study or analyzing the data.
☆☆Registration number at the clinical trials registry of the US National Library of Medicine: NCT00335257 (Please note: This is not a clinical trial.)
Identification
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© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
