Background: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. Methods: Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. Results: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified. Conclusions: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.
Bibliographical noteFunding Information:
Dr Rocha-Singh is a consultant for Medtronic Inc, Alucent Biomedical, Philips, and Pedra Technology and is a board member of VIVA Physicians. Dr Jaff is a noncompensated advisor to Boston Scientific and is a compensated advisor to Abbott Vascular, Micell, Inc, Primacea, Medtronic, Biotronik, Philips, Sanofi, Silk Road Medical, Vactronix, and Venarum. Dr Jaff is also an equity investor in Efemoral; Embolitech; Gemini; Janacare, Inc; MC 10; PQ Bypass; Primacea; Sano V, Inc; and Vascular Therapies. Dr Lyden is a noncompensated consultant to Philips and a consultant to BSC, Abbott, Endologix, Medtronic, Shockwave, and PQ Bypass and is a board member of VIVA Physicians. Dr Ansel is a consultant for Medtronic, Boston Scientific, Abbott Vascular, Surmodics, Reflow Medical, Phillips, and Veryan Inc and receives royalties from Cook Medical. Dr Ansel is also a board member of VIVA Physicians. Dr Schneider is a member of the advisory board for Medtronic, Abbott, and Boston Scientific; has served as a consultant for Surmodics, Silk Road Medical, Medtronic, Cardinal, CSI, and Profusa; is a chief medical officer for Intact Vascular and Cagent; and is a board member of VIVA Physicians. Dr, Edelman receives research funding from Abiomed, BSC, Edwards Life Sciences, and Medtronic; and consulting fees from Canon, MiCell, Peregrine, and Tekla. Dr Edelman is also an equity investor in Autus, BioDevek, and Panther. Dr Tzafriri is an employee of CBSET, Lexington, MA. Mr Mullin is an employee of NASMA, Minneapolis, MN. Dr Beckman reports consulting with AstraZeneca, Bristol-Myers Squibb, Amgen, Merck, Novo Nordisk, Sanofi, and Antidote Pharmaceutical. Dr Beckman also serves on the Drug Safety Monitoring Committee (DSMC) for Bayer and Novartis. Dr Duval was a paid statistical consultant to VIVA Physicians. The other authors report no conflicts.
VIVA Physicians, Inc., San Jose, CA., was the sole funding source of this analysis. Dr Edelman is also a recipient of grant GM49039 from the US National Institutes of Health. Dr Misra is also a recipient of grants HL098967 and DK107870 from the US National Institutes of Health and a Boehringer-Ingelheim Research Grant.
- drug-coated balloons
- drug-eluting stents
- peripheral arterial disease