Sequential Cohort Design Applying Propensity Score Matching to Analyze the Comparative Effectiveness of Atorvastatin and Simvastatin in Preventing Cardiovascular Events

Background: Sequential cohort design (SCD) applying matching for propensity scores (PS) in accrual periods has been proposed to mitigate bias caused by channeling when calendar time is a proxy for strong confounders. We studied the channeling of patients according to atorvastatin and simvastatin initiation in Finland, starting from the market introduction of atorvastatin in 1998, and explored the SCD PS approach to analyzing the comparative effectiveness of atorvastatin versus simvastatin in the prevention of cardiovascular events (CVE). Methods: Initiators of atorvastatin or simvastatin use in the 45–75-year age range in 1998–2006 were characterized by their propensity of receiving atorvastatin over simvastatin, as estimated for 17 six-month periods. Atorvastatin (10 mg) and simvastatin (20 mg) initiators were matched 1∶1 on the PS, as estimated for the whole cohort and within each period. Cox regression models were fitted conventionally, and also for the PS matched cohort and the periodically PS matched cohort, to estimate the hazard ratios (HR) for CVEs. Findings: Atorvastatin (10 mg) was associated with a 11%–12% lower incidence of CVE in comparison with simvastatin (20 mg). The HR estimates were the same for a conventional Cox model (0.88, 95% confidence interval 0.85–0.91), for the analysis in which the PS was used to match across all periods and the Cox model was adjusted for strong confounders (0.89, 0.85–0.92), and for the analysis in which PS matching was applied within sequential periods (0.88, 0.84–0.92). The HR from a traditional PS matched analysis was 0.80 (0.77–0.83). Conclusions: The SCD PS approach produced effect estimates similar to those obtained in matching for PS within the whole cohort and adjusting the outcome model for strong confounders, but at the cost of efficiency. A traditional PS matched analysis without further adjustment in the outcome model produced estimates further away from unity.