Bayes Factor Meta-Analysis of the Mortality Claim for Peripheral Paclitaxel-Eluting Devices

OBJECTIVES The aim of the present study was to quantify the probability of increased mortality with paclitaxel compared with control in a dataset of 28 randomized controlled trials. BACKGROUND Analysis of data from 28 randomized controlled trials using conventional null-hypothesis statistical testing has produced the unexpected finding of a 68% increase in mortality at 2 years and a 93% increase at 3 to 5 years after using paclitaxel-eluting balloons and stents to treat femoropopliteal arterial disease, but no biologic explanation for increased mortality has been identified. METHODS A Bayesian sequential model was developed to quantify the probability of increased mortality 1, 2, and 3 to 5 years after treatment, and p values were replaced with meta-analytic Bayes factors (BFs), which provide decisive evidence at values >100 and very strong evidence at values of 32 to 100. RESULTS The evidence for increased mortality at 1 year (BF = 0.02), 2 years (BF = 8.5), and 3 to 5 years (BF = 14.6) was less than conclusive. All-cause mortality at 1 year was similar between the paclitaxel and control arms at 1 year (odds ratio: 0.92; 95% Bayesian credible interval: 0.53 to 1.53) and 2 years (odds ratio: 1.23; 95% Bayesian credible interval: 0.84 to 1.71) but was increased at 3 to 5 years (odds ratio: 1.43; 95% Bayesian credible interval: 1.01 to 1.90). CONCLUSIONS This study finds some support for increased mortality after using paclitaxel-eluting devices in femoropopliteal arterial disease, but the evidence is not unequivocal and may not sway skeptical investigators concerned about causation, unreported studies, or the post hoc analysis of trials underpowered for mortality. (C) 2019 by the American College of Cardiology Foundation.