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Use of Statins and the Subsequent Development of Deep Vein Thrombosis
Joel G. Ray, MD, FRCPC, MSc;
Muhamad Mamdani, PharmD, MA, MPH;
Ross T. Tsuyuki, PharmD, MSc, FCSHP;
David R. Anderson, MD, FRCPC;
Erik L. Yeo, MD, FRCPC;
Andreas Laupacis, MD, FRCPC, MSc
Arch Intern Med. 2001;161:1405-1410.
Background Some of the benefit of statins for the prevention of cardiovascular
disease may be due to their antithrombotic properties. Little is known about
the effect of these drugs on the development of deep vein thrombosis.
Materials and Methods We conducted a retrospective cohort study over an 8-year period by linking
Ontario provincial health care administrative databases covering more than
1.4 million Ontario residents aged 65 years or older. We excluded those with
a documented history of atherosclerosis, venous thromboembolism, or cancer
within 36 months prior to study enrollment, as well as those prescribed warfarin
sodium within 12 months before enrollment. In the primary cohort, we evaluated
the subsequent risk of deep vein thrombosis (DVT) among men and women prescribed
thyroid replacement therapy, nonstatin lipid-lowering agents, or statins.
A second cohort of women only was evaluated in a similar fashion, but estrogen
use was added as a third comparison drug group.
Results There were 125 862 men and women in the primary cohort. After adjusting
for age; sex; prior hospitalization; newly diagnosed cancer; or prescribed
aspirin, warfarin, or estrogen, statin users (n = 77 993) had an associated
decreased risk of DVT relative to those prescribed thyroid replacement therapy
(n = 35 978) (adjusted hazard ratio [HR], 0.78; 95% confidence interval
[CI], 0.69-0.87). Compared with thyroid replacement therapy, users of nonstatin
lipid-lowering agents (n = 11 891) did not seem to be at lower risk for
deep vein thrombosis (HR, 0.97; 95% CI, 0.79-1.18). In the secondary cohort
of 89 508 women, after adjusting for age, prior hospitalization, newly
diagnosed cancer, or prescribed aspirin or warfarin, estrogen users (n = 29 165)
had an associated increased risk for DVT compared with those receiving thyroid
replacement therapy (n = 22 118) (HR, 1.16; 95% CI, 1.01-1.33), while
statin users had an associated decreased risk (HR, 0.68; 95% CI, 0.59-0.79).
Nonstatin lipid-lowering agents (n = 5155) were not associated with a reduced
risk of DVT compared with thyroid replacement therapy (HR, 0.84; 95% CI, 0.63-1.12).
Conclusion Among selected individuals aged 65 years or older, statins were associated
with a 22% relative risk reduction in the risk of DVT. A randomized clinical
trial is needed to evaluate the efficacy of statins for the primary and secondary
prevention of DVT.
From the Department of Medicine (Drs Ray, Yeo, and Laupacis), Institute
for Clinical Evaluative Sciences (Drs Mamdani and Laupacis), and the Faculty
of Pharmacy (Dr Mamdani), University of Toronto, Toronto, Ontario; Department
of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton,
Ontario (Dr Ray); EPICORE Centre, Division of Cardiology, Department of Medicine,
University of Alberta, Edmonton, Alberta (Dr Tsuyuki); and the Department
of Medicine, Dalhousie University, Halifax, Nova Scotia (Dr Anderson).
Dr
Tsuyuki has conducted research on behalf of some statin pharmaceutical companies,
none of which were involved in the current study.
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