A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A....
Transcript of A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A....
![Page 1: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/1.jpg)
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
![Page 2: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/2.jpg)
![Page 3: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/3.jpg)
No finding of paclitaxel effect on death at 6-12 months
![Page 4: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/4.jpg)
No finding of paclitaxel effect on major amputations at 6-12 months
![Page 5: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/5.jpg)
Finding of a paclitaxel effect on amputation-free survival at 6-12
months
![Page 6: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/6.jpg)
Exploratory analysis: dose effect
![Page 7: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/7.jpg)
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
![Page 8: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/8.jpg)
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
![Page 9: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/9.jpg)
120 subjects
138 subjects
85 subjects
Significant inclusion of non-peer reviewed data
~25% (343/1420)
![Page 10: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/10.jpg)
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
![Page 11: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/11.jpg)
The math is wrong: IN.PACT Deep
![Page 12: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/12.jpg)
A Consistent Error: The lost-to-follow up (LTFU) and
withdrawals (WD) are not completely/accurately accounted for in the
JAHA analysis
![Page 13: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/13.jpg)
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
![Page 14: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/14.jpg)
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
![Page 15: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/15.jpg)
Included studies with non-standard follow-up: mixed 6 month to 1 year
![Page 16: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/16.jpg)
The JAHA purported mortality effect was noted at 2 and 5 years,
but not at 1 year
![Page 17: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/17.jpg)
![Page 18: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/18.jpg)
This brings the entire proposed mechanistic explanation–which was already a tortured
one---into even further question
Hoisted by his own petard!
![Page 19: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/19.jpg)
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
![Page 20: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/20.jpg)
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
![Page 21: A Critical Appraisal of€¦ · A Critical Appraisal of JVIR CLI Paclitaxel Analysis William A. Gray MD FACC FSCAI System Chief of Cardiovascular Services President, Lankenau Heart](https://reader033.fdocuments.us/reader033/viewer/2022050311/5f7326f744e02d0928214eef/html5/thumbnails/21.jpg)
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