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on April 6, 2009

Circulation. 2009
Published online before print April 6, 2009, doi: 10.1161/CIRCULATIONAHA.108.824151
A more recent version of this article appeared on April 21, 2009
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*Statins
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Submitted on September 24, 2008
Accepted on February 11, 2009

Statin Adherence and Risk of Accidents. A Cautionary Tale

Colin R. Dormuth ScD*, Amanda R. Patrick SM, William H. Shrank MD, James M. Wright MD, PhD, Robert J. Glynn PhD, ScD, Jenny Sutherland BSc, and M. Alan Brookhart PhD

From the Therapeutics Initiative (C.R.D., J.M.W., J.S.) and Department of Anesthesiology, Pharmacology, and Therapeutics (C.R.D., J.M.W.), University of British Columbia, Vancouver, British Columbia, Canada; Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (A.R.P., W.H.S., R.J.G., M.A.B.); Department of Medicine, University of British Columbia, Vancouver, British Columbia (J.M.W.); Department of Epidemiology, Harvard School of Public Health, Boston, Mass (R.J.G.); Division of Preventative Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (R.J.G.); and Department of Biostatistics, Harvard School of Public Health, Boston, Mass (R.J.G.).

* To whom correspondence should be addressed. E-mail: colin.dormuth{at}ti.ubc.ca.

Background—Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients. We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin exposure, such as workplace and motor vehicle accidents.

Methods and Results—We conducted a prospective cohort study of statin patients using data from British Columbia, Canada, a multiethnic society with a population of 4.3 million people. Study subjects were 141 086 patients who initiated statins for primary prevention. We examined the association between adherence and multiple outcomes such as accidents and screening procedures using multivariable-adjusted Cox proportional hazards models. The study population was 49% female and had an average age of 61 years. The results from our multivariable-adjusted models showed that more adherent patients were less likely to have accidents than less adherent patients. This effect was greatest for motor vehicle accidents (hazard ratio, 0.75; 95% confidence interval, 0.72 to 0.79) and workplace accidents (hazard ratio, 0.77; 95% confidence interval, 0.74 to 0.81). More adherent patients had a greater likelihood of using screening services (hazard ratio, 1.17; 95% confidence interval, 1.15 to 1.20) and a lower likelihood of developing other diseases likely to be unrelated to a biological affect of a statin (hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89).

Conclusions—Our study contributes compelling evidence that patients who adhere to statins are systematically more health seeking than comparable patients who do not remain adherent. Caution is warranted when interpreting analyses that attribute surprising protective effects to preventive medications.


Key words: bias • confounding variables • pharmacoepidemiology • statins


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