Long-term safety data from a retrospective longitudinal study indicate that drug-coated devices (DCDs) were not linked to increased mortality when compared with non-drug-coated devices (NDCDs) for femoropopliteal endovascular revascularization. These findings were recently reported in JAMA Internal Medicine.

The investigators of SAFE-PAD (Safety Assessment of Femoropopliteal Endovascular Treatment With Paclitaxel-Coated Devices; ClinicalTrials.gov identifier: NCT04496544) sought to evaluate the real-world safety of femoropopliteal artery revascularization using either DCDs (defined as a drug-eluting stent, a drug-coated balloon with a bare metal stent, or a drug-coated balloon alone) or NDCDs (bare metal stent or angioplasty alone). The primary goal was to assess whether the mortality rate associated with DCDs was noninferior to that of NDCDs, with a 5% relative increase in mortality rate considered as the margin for noninferiority.

The study cohort included 168,553 Medicare beneficiaries aged ≥66 who were enrolled for at least 1 year before femoropopliteal revascularization. Treatment with DCDs or NDCDs was determined by claim codes. The primary study outcome was all-cause mortality; secondary outcomes were repeated hospitalization, repeated lower extremity revascularization, and lower extremity amputation. Acute myocardial infarction, congestive heart failure, and pneumonia were falsification endpoints.

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Models were weighted to correct for baseline characteristics and potential confounding. In addition, investigators performed sensitivity analyses to evaluate for potential bias of model misspecification or uncontrolled confounders. Finally, researchers repeated primary analysis and weighting methods among prespecified subgroups: treatment with stents vs balloons, low-risk patients aged 66 to 70 years with ≤2 comorbidities and no history of critical limb ischemia (CLI), patients within the lowest quartile of total comorbidities, index procedures performed in an inpatient vs outpatient setting, and patients with or without a history of CLI.

The mean age of participants was 77.0 years (SD 7.6 years), and 70,584 patients (41.9%) were treated with a DCD. Regarding comorbidities, 135,272 (80.3%) patients had hypertension; 118,567 (70.3%) had hyperlipidemia; 110,100 (65.3%) had ischemic heart disease; 85,880 (51.0%) had diabetes; 82,554 (49.0%) used tobacco; 63,796 (37.9%) had congestive heart failure; 7748 (4.6%) had acute myocardial infarction; 78,665 (45.7%) had CLI; and 13,296 (7.9%) had prior amputation.

Median follow-up time was 2.72 years, and the longest follow-up time was 5.16 years. DCDs were not associated with all-cause mortality compared with NDCDs before weighting (cumulative incidence of death, 51.6% vs 56.7%, respectively; hazard ratio [HR], 0.84; 95% CI, 0.82-0.85; P <.001) or after weighting (53.8% vs 55.1%; HR, 0.95; 95% CI, 0.94-0.97; noninferiority P <.001).

Sensitivity analyses were consistent with the primary findings, and no single covariate would have overturned the noninferiority result. Among the prespecified subgroups, survival differences were associated with DCDs including those treated with stents (HR, 0.97; 95% CI, 0.95-1.00) or balloons (HR, 0.94; 95% CI, 0.92-0.96); with CLI (HR, 0.95; 95% CI, 0.93-0.97) or without CLI (HR, 0.97; 95% CI, 0.95-0.99); or those in the low-risk subgroup (HR, 0.98; 95% CI, 0.84-1.13) or lowest comorbidities quartile (HR, 0.95; 95% CI, 0.92-0.99).

Limitations to the study included potential misclassification of device exposure, although a prior study validated the billing codes as appropriate, and the length of follow-up was relatively short at only 2.72 years. This study further lacked a medical therapy arm, which may provide more context for long-term risks. Competing causes of death in this age group may have obscured harm signals associated with these devices.

The investigators concluded that, while SAFE-PAD safety evaluations of DCDs vs NDCDs will continue until median follow-up of all patients exceeds 5 years, the current results indicate that DCDs are noninferior to NDCDs with respect to mortality in the setting of femoropopliteal endovascular treatment and are safe for real-world use. After weighting and sensitivity analyses, they wrote, the primary study findings remained robust, with DCD safety consistent across prespecified subgroups, including by device type and disease severity.

Disclosure: Multiple study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Secemsky EA, Shen C, Schermerhorn M, Yeh RW. Longitudinal assessment of safety of femoropopliteal endovascular treatment with paclitaxel-coated devices among Medicare beneficiaries. JAMA Intern Med. Published online May 16, 2021. doi: 10.1001/jamainternmed.2021.2738