The controversy about Paclitaxel-coated devices---latest evidence:

A Critical Appraisal of JVIR CLI Paclitaxel Analysis

William A. Gray MD FACC FSCAISystem Chief of Cardiovascular Services

President, Lankenau Heart InstituteWynnewood PA

USA

No finding of paclitaxel effect on death at 6-12 months

No finding of paclitaxel effect on major amputations at 6-12 months

Finding of a paclitaxel effect on amputation-free survival at 6-12

months

Exploratory analysis: dose effect

Inadequate numbers to construct a study-level meta-analysis with significant risk of Type I error (False positive)

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISM) Flowchart

~1400 subjects

Where have we seen this before?JAHA SFA meta-analysis also fell short

in the relevant time period

Enrollment by duration of trial follow up

4663

4432

2316

863

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Initial Year 1 Year 2 Year 5

# of Patients

# of Patients

28 RCT

28 RCT

12 RCT

3 RCT

Main Line HealthLankenau Heart Institute

120 subjects

138 subjects

85 subjects

Significant inclusion of non-peer reviewed data

~25% (343/1420)

A Consistent Error:

PTA group is likely not paclitaxel naïve for the entirety of the analysis

• Paclitaxel device approvals in EU and US preceded all of the trial data

• Prior use in proximal, contra-lateral lesions during or prior to the trial is not known

• This was also a problem with the prior JAHA analysis

– Not possible in a study-level analysis---requires patient level data

The math is wrong: IN.PACT Deep

A Consistent Error: The lost-to-follow up (LTFU) and

withdrawals (WD) are not completely/accurately accounted for in the

JAHA analysis

THUNDER trial

After WD and LTFU:mortality at 5 years=

33% (12/36) and 28% (8/29)

RR: 1.17 (not 1.69)

At year 2Control: 12 LTFU DCB: 4 LTFU

At year 5Control: 13 LTFU DCB: 7 LTFU

Dose “analysis” is highly flawed

• No lesion length, number of balloons used, or adjustments for selection bias or cross-trial differences

• Inconsistent with prior Katsanos methodology

Included studies with non-standard follow-up: mixed 6 month to 1 year

The JAHA purported mortality effect was noted at 2 and 5 years,

but not at 1 year

This brings the entire proposed mechanistic explanation–which was already a tortured

one---into even further question

Hoisted by his own petard!

Summary

This “analysis” is very poorly constructed and conducted, and therefore should have no meaningful impact on this high-risk, in-need CLI population, especially given the

marked improvement in patency documented in the same manuscript

Shame on JVIR

• The poor conduct and construct of this analysis is evident to even a cursory review

• Therefore, one can only assume that the editors knowingly allowed the publication of poor science

• Their motives can only be speculated on…

• But their downgrade in standards should be clear to everyone, and should be called out

The controversy about Paclitaxel-coated devices---latest evidence:

A Critical Appraisal of JVIR CLI Paclitaxel Analysis

William A. Gray MD FACC FSCAISystem Chief of Cardiovascular Services

President, Lankenau Heart InstituteWynnewood PA

USA