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 (BC), Canada, a multi-ethnic 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. 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 [HR] 0.75; 95% confidence interval [CI], 0.72 – 0.79) and workplace accidents (HR 0.77; 95% CI, 0.74 – 0.81). More adherent patients had a greater likelihood of using screening services (HR 1.17; 95% CI, 1.15 – 1.20) and a lower likelihood of developing other diseases likely to be unrelated to a biological affect of a statin (HR 0.87; 95% CI 0.86 – 0.89).
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.
Keywords: confounding bias, healthy user effect, adherence bias, pharmacoepidemiology, epidemiological methods, statins