Systematic Evidence Review

Number 11

Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 2101 East Jefferson Street Rockville, MD 20852

http://www.ahrq.gov/

Contract No. 290-97-0018 Task Order No. 2 Technical Support of the U.S. Preventive Services Task Force

Prepared by: Oregon Health Sciences University Evidence-based Practice Center, Portland, Oregon Jill Miller, MD Benjamin K.S. Chan, MS Heidi Nelson, MD, MPH

August 2002

This report may be used, in whole or in part, as the basis for development of clinical practice gdelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers -- patients and clinicians, health system leaders, and policymakers -- make more informed decisions and improve the quality of health care services.

The Agency for Healthcare Research and Quality (AHRQ) sponsors the development of Systematic Evidence Reviews (SERs) through its Evidence-based Practice Program. With gdance from the third U.S. Preventive Services Task Force* (USPSTF) and input from Federal partners and primary care specialty societies, two Evidence-based Practice Centers -- one at the Oregon Health Sciences University and the other at Research Triangle Institute-University of North Carolina -- systematically review the evidence of the effectiveness of a wide range of clinical preventive services, including screening, counseling, immunizations, and chemoprevention, in the primary care setting. The SERs -- comprehensive reviews of the scientific evidence on the effectiveness of particular clinical preventive services -- serve as the foundation for the recommendations of the third USPSTF, which provide age- and risk-factor-specific recommendations for the delivery of these services in the primary care setting. Details of the process of identifying and evaluating relevant scientific evidence are described in the "Methods" section of each SER.

The SERs document the evidence regarding the benefits, limitations, and cost-effectiveness of a broad range of clinical preventive services and will help to further awareness, delivery, and coverage of preventive care as an integral part of quality primary health care.

AHRQ also disseminates the SERs on the AHRQ Web site (http://www.ahrq.gov/uspstfix.htm) and disseminates summaries of the evidence (summaries of the SERs) and recommendations of the third USPSTF in print and on the Web. These are available through the AHRQ Web site (http://www.ahrgq.gov/uspstfix.htm), through the National Gdeline Clearinghouse (http://www.ncg.gov), and in print through the AHRQ Publications Clearinghouse (1-800-358-9295).

We welcome written comments on this SER. Comments may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 6010 Executive Blvd., Ste 300, Rockville, MD 20852.

Although postmenopausal hormone replacement therapy is widely used, its risks and benefits are not well understood.

To assess the risk of venous thromboembolism with the use of postmenopausal hormone replacement therapy (HRT) by literature review and meta-analysis.

All relevant English-language studies identified in MEDLINE (1966 to December 2000), HealthSTAR (1975 to December 2000), Cochrane library databases, and reference lists of key articles. Studies of selective estrogen receptor modulators (SERMs) were identified in MEDLINE (1991 to December 2000).

All studies of postmenopausal HRT or SERMs reporting venous thromboembolism as an outcome or adverse event.

Twelve studies of HRT (3 randomized controlled trials, 8 case-control studies, and one cohort study), and 5 randomized controlled trials of SERMs were identified. We extracted data on number of participants, interventions, event rates, and confounders. Two reviewers independently rated study quality based on established criteria.

We used Bayesian meta-analysis. Current HRT use was associated with an increased risk of venous thromboembolism (relative risk [RR], 2.14; CI, 1.64-2.81). The absolute rate increase was 1.5 venous thromboembolic events per 10,000 women in one year. Five case-control studies reported highest risk within the first year of use (odds ratios [OR], 2.9-6.7). Data from 5 randomized controlled trials of SERMs were not included in the meta-analysis. The 2 largest trials reported a similar increased risk of venous thromboembolism.

Postmenopausal HRT is associated with an increased risk of venous thromboembolism, and this risk may be highest in the first year of use. SERMs are associated with a similar increase in risk.