Author + information
- Received June 27, 2019
- Revision received August 20, 2019
- Accepted September 4, 2019
- Published online December 16, 2019.
- John A. Bittl, MDa,∗ (, )
- Yulei He, PhDb,
- Usman Baber, MDc,
- Robert L. Feldman, MDa,
- Gregory O. von Mering, MDd and
- Sanjay Kaul, MDe
- aDepartment of Interventional Cardiology, AdventHealth Ocala, Ocala, Florida
- bProgram in Mathematics and Statistics, University of Maryland University College, Largo, Maryland
- cIcahn School of Medicine at Mt. Sinai, New York, New York
- dUniversity Hospital, University of Alabama, Birmingham, Alabama
- eCedars-Sinai Medical Center, Los Angeles, California
- ↵∗Address for correspondence:
Dr. John A. Bittl, Department of Interventional Cardiology, AdventHealth Ocala, 1221 SE 5th Street, Ocala, Florida 34471.
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.
Drs. Feldman and von Mering serve as consultants to Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 27, 2019.
- Revision received August 20, 2019.
- Accepted September 4, 2019.
- 2019 American College of Cardiology Foundation
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