The American Journal of Medicine
Volume 123, Issue 1 , Page 3, January 2010

Statins to Prevent Venous Thromboembolism in Patients with Cancer?

University of Arizona College of Medicine, Tucson

Article Outline

 

Multiple case-control studies have documented that patients receiving long-term statins, but not other non-statin lipid-lowering drugs, have a decreased incidence of venous thromboembolism. This was first reported by Grady et al1 in a report from the Heart and Estrogen/Progestin Replacement Study, in which women with coronary artery disease were randomized to receive estrogen or placebo. The incidence of subsequent venous thromboembolism was increased in women receiving estrogen. However, women given estrogen who were receiving statin therapy had a 50% lower incidence of venous thromboembolism than those not receiving statin therapy.

Ray et al2 reported a retrospective cohort study of patients aged 65 years or more who had been prescribed thyroid, statins, or non-statin lipid-lowering agents. The incidence of deep vein thrombosis in 77,993 statin users was lower than in patients prescribed thyroid (odds ratio 0.78; confidence interval, 0.69-0.87). The incidence of deep vein thrombosis in those taking non-statin lipid-lowering agents was not reduced.

Sorenson et al3 compared the prevalence of statin use in 5824 patients with an initial diagnosis of venous thromboembolism with 58,240 controls. The odds ratio of venous thromboembolism in statin users was 0.74 (0.63-0.85).

The first randomized clinical trial to demonstrate that statins reduce the incidence of venous thromboembolism was reported by Glynn et al.4 In the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin, 17,802 men and women with low-density lipoprotein levels less than 130 mg/dL and high-sensitivity C-reactive protein greater than 2.0 mg/L were randomized to rosuvastatin (20 mg/d) or placebo. After 1.9 years follow-up, the incidence of venous thromboembolism was 0.18 per year in those taking rosuvastatin compared with 0.32 per year in those taking placebo (odds ratio 0.57; confidence interval, 0.37-0.86; P=.007). This reduction in venous thromboembolism is judged to be due to the antithrombotic properties of statins.5 Patients taking statins for the prevention of cardiovascular events have an additional benefit of a modest reduction in venous thromboembolism, which is infrequent in the general population.

Given the results of the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin,4 is there a group of patients at significant risk of venous thromboembolism such that a randomized clinical trial of statin versus placebo to reduce the incidence of venous thromboembolism would be appropriate?

The risk of venous thromboembolism in patients undergoing hip and knee replacement is sufficiently high that prophylactic therapy with anticoagulants is the standard of care in these patients. A randomized clinical trial of statin versus placebo would not be appropriate.

In this issue of the Journal, Khemasuwan et al6 examines statin use in 740 consecutive patients with solid-organ tumors. The overall incidence of venous thromboembolism within 2 months of diagnosis was 18%: 21% in those not receiving statins and 8% in those receiving statins (odds ratio 0.33; confidence interval, 0.19-0.57).

Although there is a significant incidence of venous thromboembolism in patients being treated for cancer, prophylactic therapy with anticoagulants is not the standard of care because of the risk of bleeding complications. Because statins do not cause bleeding and have minimal side effects, patients undergoing therapy for cancer might be an appropriate group for a randomized clinical trial of statins versus placebo to prevent venous thromboembolism.

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References 

  1. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. Ann Intern Med. 2000;132:689–696
  2. Ray JG, Mamdani M, Tsuyuki RT, et al. Use of statins and the subsequent development of deep vein thrombosis. Arch Intern Med. 2001;161:1405–1410
  3. Sorenson HT, Horvath-Puho E, Sogaard KK, et al. Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case-control study. J Thromb Haemost. 2009;7:521–528
  4. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851–1861
  5. Kearney D, Fitzgerald D. The anti-thrombotic effects of statins. J Am Coll Cardiol. 1999;33:1305–1307
  6. Khemasuwan D, DiVietro ML, Tangdhanakanond K, et al. Statins decrease the occurrence of venous thromboembolism in patients with cancer. Am J Med. 2010;123:60–65

PII: S0002-9343(09)00708-6

doi:10.1016/j.amjmed.2009.07.013

The American Journal of Medicine
Volume 123, Issue 1 , Page 3, January 2010

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