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Source: Ray JG, et al. Arch Intern Med. 2001;161:1405-1410.
This paper is actually 2 retrospective analyses of large cohorts of individuals at risk for deep venous thrombosis (DVT). In the first analysis, they calculated the hazard ratio for new DVT development in 125,862 Ontarians who were free of documented atherosclerosis, venous thromboembolism, or cancer in the prior 3 years. The mean age of participants was 72.9 years, and the observation period was 1.4 years. Of these patients, 77,993 were statin users and had a hazard ratio of 0.78 (CI, 0.69-0.87) for new DVT development compared with those who used thyroid replacement therapy. These findings were controlled for age, gender, prior hospitalization, new cancer, and treatment with aspirin, coumadin, or estrogen. Those individuals who used nonstatin lipid-lowering agents did not show a similar reduction in DVT risk. In the second analysis of 89,508 women, Ray and colleagues found that those women who were taking estrogen replacement therapy (n = 29,165) were at increased risk for DVT (hazard ratio, 1.16; CI, 1.01-1.33) compared with those who were not. Statins appeared to lower that risk (hazard ratio 0.68; CI 0.59-0.79) compared with those receiving thyroid replacement therapy. This reduction was not seen with nonstatin lipid-lowering agents.
Comment by Barbara A. Phillips, MD, MSPH
Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are in widespread use to prevent cardiovascular disease in people with elevated lipid levels. Ray et al undertook the current study because the Heart Estrogen Replacement Study (HERS) suggested a 50% risk reduction of venous thromboembolism in women who used statins.1 Because the HERS study was not designed to evaluate this effect of statins, further specific investigation of their effects on DVT development is warranted. This study is an important step in that direction.
Ray et al make several interesting observations in their discussion. First, the rate of spontaneous discontinuation of lipid-lowering medications by patients is very high; at least half of patients stop taking these meds within a year of the initial prescription, most within the first 3 months.2,3 This may not be true in Ontario, where, as Ray et al proudly proclaim, "The Ontario Health Insurance Plan covers all medical care and prescription drug costs for every Ontario Senior Citizen." Second, the rate of DVT development in older women on estrogen replacement therapy may be much higher than previously recognized. In this study, the rate of DVT and pulmonary embolism in women on estrogen was 12.6 per 1000 person years, twice that seen in the HERS study.1 Ray et al point out that the women in the HERS study were younger and were more likely to be on aspirin or lipid-lowering agents because they were known to have coronary heart disease. For me, the take home messages are to lower the threshold to prescribe statins, particularly in women on estrogen replacement therapy, and to regularly encourage their use.
1. Grady D, et al. Ann Intern Med. 2000;132:689-696.
2. Simons LA, Levis G, Simons J. Med J Aust. 1996;164: 208-211.
3. Avorn J, et al. JAMA. 1998;279:1458-1462.
Dr. Phillips is Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, Ky.