External Adjustment Sensitivity Analysis for Unmeasured Confounding: An Application to Coronary Stent Outcomes, Pennsylvania 2004–2008

Abstract

Background. Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. Objective. To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/ tests for confounding. Data Sources/Study Setting. Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004-2005 followed up for death through 3 years. Study Design. Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. Principal Findings. DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Conclusions. Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population.

Improved Adverse Postoperative Outcomes With Revised American College of Cardiology/American Heart Association Guidelines for Patients With Cardiac Stents

“…However, both propensity-matching and instrumental variable analyses have failed to provide a c l e a r e x p l a n a t i o n o f c o n f o u n d i n g b y s t e n t t y p e selection. [21][22][23] While our study cannot adequately account for this confounding, it does provide further evidence of a shift toward higher risk in patients with a BMS.…”

“…Finally, there was a shift toward earlier operations with more recent MI and CHF episodes in the population with BMSs, providing further evidence of selection bias that prior studies have struggled to thoroughly describe. 22 This shift parallels higher postoperative MACE rates among patients with BMSs; however, in the years following the guidelines, patients with DESs saw a continued decline in postoperative MACE rates, while MACE rates in patients with BMSs appeared to return to baseline. When examined as a dichotomous variable, it would appear that the guidelines were successful at changing practices in surgery timing as well as reducing MACE rates.…”