The Improving Prognosis of Peripheral Artery Disease patients undergoing EVT in Nagano, Japan (I-PAD Nagano) registry was a prospective, multicenter, observational registry designed to provide up to 60 months of clinical follow-up. A total of 366 patients undergoing EVT for symptomatic PAD were enrolled at 11 institutions between August 2015 and August 2016. For the current subanalysis, patients not undergoing coronary angiography or those without significant coronary artery stenosis were excluded. Patients were divided into the following two groups: the CR group and incomplete revascularization (ICR) group. The I-PAD registry was approved by the medical ethics committee of the Shinshu University School of Medicine (No. 3187). The study and procedures were conducted in accordance with the Declaration of Helsinki. A written informed consent was taken from the enrolled patients. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry, as accepted by the International Committee of Medical Journal Editors (No. UMIN000018297).

CAD was defined as ≥ 50% stenosis of a coronary artery on angiography, or a history of coronary artery bypass graft surgery, PCI, or myocardial infarction. CR was defined as residual Syntax score = 0 [13]. The SYNTAX score is the sum of the points assigned to each individual lesion identified in the coronary tree with > 50% diameter narrowing in vessels > 1.5-mm diameter. Each segment is given a score of 1 or 2 based on the presence of disease. Subsequently, this score is weighted based on a chart, with values ranging from 3.5 for the proximal left anterior descending artery to 5.0 for left main, and 0.5 for smaller branches [14]. Cerebrovascular disease was defined according to the hospital or a reported diagnosis of transient ischemic attack or ischemic stroke by a neurologist. Heart failure was defined as a previous diagnosis of heart failure, history of hospitalization for heart failure, or current treatment for heart failure. Diabetes mellitus was defined as a hemoglobin A1c level of ≥ 6.5%, random plasma glucose ≥ 200 mg/dL or treatment with oral hypoglycemic agents or insulin injection. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or ongoing therapy for hypertension. Dyslipidemia was defined as a serum cholesterol concentration of ≥ 220 mg/dL, a low-density lipoprotein cholesterol concentration of ≥ 140 mg/dL, or current treatment with lipid lowering agents. Chronic limb-threatening ischemia (CLTI) was defined as a patient with objectively documented PAD and any of the clinical symptoms or signs of ischemic rest pain with confirmatory hemodynamic studies or gangrene involving any portion of the lower limb or foot, except for pure venous ulcers, pure traumatic wounds, acute limb ischemia (symptoms present for two weeks or less), embolic disease, and nonatherosclerotic chronic vascular conditions of the lower extremity (e.g., vasculitis, Buerger disease, radiation arteritis). Body mass index was defined as weight in kilograms divided by the square of the patient’s height in meters. Estimated glomerular filtration (eGFR) was calculated with the following formula: male: eGFR (mL/min/1.73m²) = 194 × creatinine (Cr)^−1.094 × age^−0.287, female: eGFR = 194 × Cr^−1.094 × age^−0.287 × 0.739.

Primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction, and stroke at five years. Secondary endpoints were survival and major adverse cardiovascular and leg events (MACLE), defined as a composite of all-cause death, myocardial infarction, stroke, major amputation, reintervention for PAD. Myocardial infarction (MI) was defined according to the 3rd universal definition of MI [15]. Target extremity revascularization included either EVT or a surgical procedure [16]. All above-ankle amputations were considered a major amputation [17].

Continuous variables were reported as median (interquartile range) and compared by using Wilcoxon-Mann–Whitney U tests, as appropriate. Categorical data were calculated as frequencies (percentages) and were compared with the chi-square test. Survival curves were constructed for time-event variables with Kaplan–Meier estimates and compared using the log-rank test. Cox regression analysis was performed to test the prognostic significance of complete revascularization for MACE. CR was adjusted by clinically important variables reported by previous studies [18‐22]. A P value < 0.05 was considered statistically significant in all analyses. Data were analyzed using JMP 11 (SAS Institute, Cary, NC).

Of 366 patients enrolled in the I-PAD Nagano registry, those who did not undergo coronary angiography (n = 45) or those who did not have significant coronary artery stenosis (n = 157) were excluded. As a result, 164 patients were analyzed for the current study (CR group: n = 96, ICR group: n = 68) (Fig. 1). In the CR group, CR with PCI was performed within 6 months after EVT. Baseline characteristics are summarized in Tables 1 and 2. There were no significant differences in baseline characteristics between groups. A median residual Syntax score in the ICR group was 6.

Kaplan–Meier analysis for clinical outcomes were summarized in Fig. 2. The freedom from MACE was significantly higher in the CR group compared with the ICR group (66.7% vs. 46.0%, p < 0.01) (Fig. 2A). The survival was significantly higher in the CR group than in the ICR group (71.0% vs. 53.8%, p = 0.01) (Fig. 2B). There was no significant difference in MACLE (46.2% vs. 36.0%, respectively, p = 0.24) (Fig. 2C). CR was significantly associated with a lower risk of MACE among patients < 75 years (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.13–0.72), those without hemodialysis (HR 0.40, 95%CI 0.21–0.77), those with low frailty scale (i.e. < 5) (HR 0.41, 95%CI 0.21–0.80), and those with CLTI (HR 0.49, 95%CI 0.24–0.97), whereas no significant interaction was observed across patient subsets in a stratified analysis (Fig. 3). There were 55 deaths in the current study (CR 28 vs ICR 27); the major cause of death was cardiac death in both groups (CR 7.3% vs. ICR 13.2%) (Fig. 4).

The results of multivariable Cox regression analysis for MACE are shown in Table 3. CR of the coronary artery (HR 0.56, 95%CI 0.34–0.94, p = 0.03), age (HR 1.04, 95%CI 1.01–1.08, p < 0.01), body mass index (HR 0.87, 95%CI 0.80–0.94, p < 0.01), hemodialysis (HR 2.63, 95%CI 1.41–4.72, p < 0.01), CLTI (HR 2.29, 95%CI 1.36–3.85, p < 0.01), and heart failure (HR: 2.71, 95% CI: 1.51–4.84, p < 0.01) were significantly associated with MACE.