Two years ago a study raised concerns that paclitaxel-coated devices may cause increased mortality in peripheral artery disease patients. However, numerous studies now show there is no risk of increased mortality. The most recent study is the SAFE-PAD study presented at ACC.21.
June 7, 2021 — A couple years ago a study showed a mortality safety signal in patients who underwent peripheral artery disease (PAD) revascularization with paclitaxel drug-coated devices. This immediately raised alarm in with the U.S. Food and Drug Administration (FDA) and the interventional community and prompted numerous studies to confirm if there was a mortality signal, or if the findings were just coincidence. The latest study is SAFE-PAD, which showed drug-coated devices are noninferior to non-drug-coated devices for all-cause mortality in Medicare beneficiaries who had femoropopliteal revascularization.
The initial report from the SAFE-PAD study was presented May 16 in a Featured Clinical Research session during the ACC 2021 annual meeting, and simultaneously published in JAMA Internal Medicine.
Eric A. Secemsky, M.D., MSc, FACC, et al., designed this retrospective cohort study with feedback from the U.S. Food and Drug Administration (FDA) to provide a longitudinal assessment of the safety of the drug-coated devices in this setting because of data from meta-analyses of small trials showing an association between drug-coated devices and increased mortality.
Among 168,553 Medicare fee-for-service beneficiaries (45% women, 82% white, mean age 77 years) who underwent femoropopliteal artery revascularization from 2015 through 2018, 51% had diabetes, 49% used tobacco, 46% had critical limb ischemia (CLI), and 8% had a previous amputation. A drug-coated device was used in 41.9%.
Results showed that after weighting, cumulative all-cause mortality over the median 2.72 years of follow-up (longest, 5.16 years) was 53.8% with drug-coated devices and 55.1% with non-drug-coated devices (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97; noninferiority p<0.001). Sensitivity analyses were consistent and robust for the primary outcome.
This finding with drug-coated devices was consistent across prespecified subgroups, including treatment with stents or balloons, presence or absence of CLI, and the lowest quartile of total morbidities.
"SAFE-PAD will continue until the median follow-up of all patients surpasses 5 years and will provide the FDA a mechanism for the ongoing safety evaluation of these devices," write the authors. "Furthermore, SAFE-PAD may serve as a case example of how to leverage real-world evidence to provide timely device safety evaluations."
In a related editorial comment, Rita F. Redberg, M.D., MSc, FACC, and Mary M. McDermott, M.D., wrote "this analysis did not confirm the signal of harm seen in the [randomized clinical trials]." However, they explain that it raises "new and important questions" about the high rates of mortality in this population undergoing endovascular revascularization, and note that more than half of patients with [peripheral artery disease (PAD)] died during the 2.7 years of follow-up. Furthermore, patients with PAD have higher rates of death from cardiovascular events, and "recent evidence shows a high rate of death from cancer and infection" in PAD. Thus, there should be a continued focus on conservative treatment, including smoking cessation and exercise therapy to improve quality of life, they conclude.
Related Paclitaxel Safety Content:
1. Eric A. Secemsky,Changyu Shen, Marc Schermerhorn, et al. Longitudinal Assessment of Safety of Femoropopliteal Endovascular Treatment With Paclitaxel-Coated Devices Among Medicare Beneficiaries. The SAFE-PAD Study. JAMA Intern Med. Published online May 16, 2021. doi:10.1001/jamainternmed.2021.2738.