Dataset Information

Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel Distributed Database.

ABSTRACT:

Importance

Continuous/extended cyclic estrogen use (84/7 or 365/0 days cycles) in combined oral contraceptives (COCs) could potentially expose women to an increased cumulative dose of estrogen, compared with traditional cyclic regimens (21/7 days cycle), and may increase the risk for venous thromboembolism (VTE).

Objective

To determine, while holding the progestogen type constant, whether the risk for VTE is higher with use of continuous/extended COCs than with cyclic COCs among women who initiated a COC containing ethinyl estradiol and levonorgestrel.

Design, setting, and participants

Incident user retrospective cohort study of primarily commercially insured US population identified from the Sentinel Distributed Database. Participants were women aged 18 to 50 years at the time of initiating a study COC between May 2007 and September 2015. Using a propensity score approach and Cox proportional hazards regression models, we estimated the hazard ratios of VTE overall and separately by ethinyl estradiol dose and age groups.

Exposures

Initiation of continuous/extended or traditional cyclic COCs containing ethinyl estradiol or levonorgestrel of any dose.

Main outcomes and measures

First VTE hospitalization that occurred during the study follow-up, identified by an inpatient International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of 415.1, 415.1x, 453, 453.x, or 453.xx.

Results

We identified 210?691 initiators of continuous/extended COCs (mean [SD] age, 30.4 [8.6] years) and 522?316 initiators of cyclic COCs (mean [SD] age, 28.8 [8.3] years), with a mean of 0.7 person-years at risk among continuous/extended and cyclic users. Baseline cardiovascular and metabolic conditions (7.2% vs 4.7%), gynecological conditions (39.7% vs 32.3%), and health services utilization were slightly higher among continuous/extended cyclic than cyclic COC users. Propensity score matching decreased the hazard ratio estimates from 1.84 (95% CI, 1.53-2.21) to 1.32 (95% CI, 1.07-1.64) for continuous/extended use compared with cyclic COC use. The absolute risk difference (0.27 per 1000 persons) and the incidence rate difference (0.35 cases per 1000 person-years [1.44 vs 1.09 cases per 1000 person-years]) between the 2 propensity score-matched cohorts remained low, which may not translate into a clinically significant risk differences between cyclic and noncyclic estrogen use.

Conclusions and relevance

Holding the progestogen type constant (levonorgestrel), we observed a slightly elevated VTE risk in association with continuous/extended COC use when compared with cyclic COC use. However, due to the small absolute risk difference and potential residual confounding, our findings did not show strong evidence supporting a VTE risk difference between continuous/extended and cyclic COC use.

SUBMITTER: Li J

PROVIDER: S-EPMC6248208 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel Distributed Database.

Li Jie J Panucci Genna G Moeny David D Liu Wei W Maro Judith C JC Toh Sengwee S Huang Ting-Ying TY

JAMA internal medicine 20181101 11

<h4>Importance</h4>Continuous/extended cyclic estrogen use (84/7 or 365/0 days cycles) in combined oral contraceptives (COCs) could potentially expose women to an increased cumulative dose of estrogen, compared with traditional cyclic regimens (21/7 days cycle), and may increase the risk for venous thromboembolism (VTE).<h4>Objective</h4>To determine, while holding the progestogen type constant, whether the risk for VTE is higher with use of continuous/extended COCs than with cyclic COCs among w ...[more]

PMID: 30285041

Similar Datasets

Project description:Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i.e., ethinylestradiol (EE), was significantly reduced. New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel. Numerous studies assessed the impact of estroprogestative combinations on hemostasis and demonstrated that women under COC suffered from resistance towards activated protein C (APC). Subsequently, the European Medicines Agency updated its guidelines on clinical investigation of steroid contraceptives in which they recommended to assess this biological marker. In 2009, estradiol-containing COCs were marketed and the use of this natural form of estrogen was found to exert a weaker effect on the synthesis of hepatic proteins compared to EE. In this year 2021, a novel COC based on a native estrogen, i.e., estetrol, will be introduced on the market. Associated with drospirenone, this preparation demonstrated minor effects on coagulation proteins as compared with other drospirenone-containing COCs. At the present time, the standard of care when starting a contraception, consists of identifying the presence of hereditary thrombophilia solely on the basis of familial history of VTE. This strategy has however been reported as poorly predictive of hereditary thrombophilia. One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.

Project description:BackgroundThe present study characterized the incidence of venous thromboembolism in a contemporary cohort of surgical oncology patients and its association with index hospitalization and postdischarge outcomes.MethodsAdults undergoing 7 major thoracic and abdominal cancer resections were identified in the 2016-2019 Nationwide Readmissions Database. Multivariable models stratified by operative subtype were developed to evaluate the association of venous thromboembolism with outcomes of interest.ResultsOf an estimated 436,368 patients, venous thromboembolism was identified in 9,811 (2.2%) patients during index hospitalization. Esophageal (4.1%) and gastric (4.1%) resections exhibited the highest rates of venous thromboembolism, whereas pulmonary resection (1.0%) the lowest. Following adjustment, cancer resection type demonstrated the strongest association with venous thromboembolism development among all factors analyzed (adjusted odds ratio: 3.13, 95% confidence interval: 2.60-3.78). Diagnosis of venous thromboembolism was associated with increased mortality (10.2%, 95% confidence interval: 9.4-11.1 vs 1.7, 95% confidence interval: 1.6-1.7) and prolonged index hospital stay (19.5 days, 95% confidence interval: 19.1-20.0 vs 7.5, 95% confidence interval: 7.4-7.5). Of patients who survived index hospitalization, venous thromboembolism occurrence was associated with increased risk of nonhome discharge (56.4%, 95% confidence interval: 54.7-58.0 vs 14.4, 95% confidence interval: 14.2-14.7) and readmission (30.0%, 95% confidence interval: 28.5-31.1 vs 16.9, 95% confidence interval: 16.7-17.1). Additionally, venous thromboembolism substantially increased index hospitalization ($40,000, 95% confidence interval: $38,000-$42,000) and readmission costs ($3,200, 95% confidence interval: $1,700-$4,700).ConclusionRates of venous thromboembolism remain high in surgical oncology patients, with cancer resection type as a major predictor of venous thromboembolism incidence. Venous thromboembolism was associated with inferior clinical and financial outcomes that extended beyond discharge. These findings underscore the importance of continued vigilance and procedure-specific prophylaxis measures.

Dataset Information

Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel Distributed Database.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel Distributed Database.

Similar Datasets

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