Comparing marginal structural models to standard methods for estimating treatment effects of antihypertensive combination therapy

作者：Gerhard Tobias^*; Delaney Joseph A C; Cooper DeHoff Rhonda M; Shuster Jonathan; Brumback Babette A; Johnson Julie A; Pepine Carl J; Winterstein Almut G

来源：BMC Medical Research Methodology, 2012, 12: 119.

DOI：10.1186/1471-2288-12-119

• Blood pressure
• Hypertension
• Time-dependent confounding
• Marginal structural models

Background: Due to time-dependent confounding by blood pressure and differential loss to follow-up, it is difficult to estimate the effectiveness of aggressive versus conventional antihypertensive combination therapies in non-randomized comparisons.
Methods: We utilized data from 22,576 hypertensive coronary artery disease patients, prospectively enrolled in the INternational VErapamil-Trandolapril STudy (INVEST). Our post-hoc analyses did not consider the randomized treatment strategies, but instead defined exposure time-dependently as aggressive treatment (>= 3 concomitantly used antihypertensive medications) versus conventional treatment (<= 2 concomitantly used antihypertensive medications). Study outcome was defined as time to first serious cardiovascular event (non-fatal myocardial infarction, non-fatal stroke, or all-cause death). We compared hazard ratio (HR) estimates for aggressive vs. conventional treatment from a Marginal Structural Cox Model (MSCM) to estimates from a standard Cox model. Both models included exposure to antihypertensive treatment at each follow-up visit, demographics, and baseline cardiovascular risk factors, including blood pressure. The MSCM further adjusted for systolic blood pressure at each follow-up visit, through inverse probability of treatment weights.
Results: 2,269 (10.1%) patients experienced a cardiovascular event over a total follow-up of 60,939 person-years. The HR for aggressive treatment estimated by the standard Cox model was 0.96 (95% confidence interval 0.87-1.07). The equivalent MSCM, which was able to account for changes in systolic blood pressure during follow-up, estimated a HR of 0.81 (95% CI 0.71-0.92).
Conclusions: Using a MSCM, aggressive treatment was associated with a lower risk for serious cardiovascular outcomes compared to conventional treatment. In contrast, a standard Cox model estimated similar risks for aggressive and conventional treatments.

• 出版日期2012-8-6