Long-term Follow-up of a Randomized Clinical Trial Comparing Endovascular Revascularization Plus Supervised Exercise With Supervised Exercise Only for Intermittent Claudication.

OBJECTIVE: The goal of this study was to assess the long-term effectiveness of combination therapy for intermittent claudication, compared with supervised exercise only. BACKGROUND: Supervised exercise therapy is recommended as first-line treatment for intermittent claudication by recent guidelines. Combining endovascular revascularization plus supervised exercise shows promising results; however, there is a lack of long-term follow-up. METHODS: The ERASE study is a multicenter randomized clinical trial, including patients between May 2010 and February 2013 with intermittent claudication. Interventions were combination of endovascular revascularization plus supervised exercise (n = 106) or supervised exercise only (n = 106). Primary endpoint was the difference in maximum walking distance at long-term follow-up. Secondary endpoints included differences in pain-free walking distance, ankle-brachial index, quality of life, progression to critical limb ischemia, and revascularization procedures during follow-up. This randomized trial report is based on a post hoc analysis of extended follow-up beyond that of the initial trial. Patients were followed up until 31 July 2017. Data were analyzed according to the intention-to-treat principle. RESULTS: Median long-term follow-up was 5.4 years (IQR 4.9-5.7). Treadmill test was completed for 128/212 (60%) patients. Whereas the difference in maximum walking distance significantly favored combination therapy at 1-year follow-up, the difference at 5-year follow-up was no longer significant (53 m; 99% CI-225 to 331; P = 0.62). No difference in pain-free walking distance, ankle-brachial index, and quality of life was found during long-term follow-up. We found that supervised exercise was associated with an increased hazard of a revascularization procedure during follow-up (HR 2.50; 99% CI 1.27-4.90; P < 0.001). The total number of revascularization procedures (including randomized treatment) was lower in the exercise only group compared to that in the combination therapy group (65 vs 149). CONCLUSIONS: Long-term follow up after combination therapy versus supervised exercise only, demonstrated no significant difference in walking distance or quality of life between the treatment groups. Combination therapy resulted in a lower number of revascularization procedures during follow-up but a higher total number of revascularizations including the randomized treatment. TRIAL REGISTRATION: Netherlands Trial Registry Identifier: NTR2249.

Supervised exercise therapy and revascularization: Single-center experience of intermittent claudication management.

Guidelines recommend supervised exercise therapy (SET) as first-line treatment for intermittent claudication. However, the use of revascularization is widespread. We addressed the effectiveness of preventing (additional) invasive revascularization after primary SET or revascularization based on lesion and patient characteristics. In this single-center, retrospective, cohort study, 474 patients with intermittent claudication were included. Patients with occlusive disease of the aortoiliac tract and/or common femoral artery (inflow) were primarily considered for revascularization, while patients with more distal disease (outflow) were primarily considered for SET. In total, 232 patients were referred for SET and 242 patients received revascularization. The primary outcome was freedom from (additional) intervention, analyzed by Kaplan-Meier estimates. Secondary outcomes were survival, critical ischemia, freedom from target lesion revascularization (TLR), and an increase in maximum walking distance. In the SET-first strategy, 71% of patients had significant outflow lesions. Freedom from intervention was 0.90 ± 0.02 at 1-year and 0.82 ± 0.03 at 2-year follow-up. In the primary revascularization group, 90% of patients had inflow lesions. Freedom from additional intervention was 0.78 ± 0.03 at 1-year and only 0.65 ± 0.04 at 2-year follow-up, despite freedom from TLR of 0.91 ± 0.02 and 0.85 ± 0.03 at 1- and 2-year follow-up, respectively. In conclusion, SET was effective in preventing invasive treatment for patients with mainly outflow lesions. In contrast, secondary intervention rates following our strategy of primary revascularization for inflow lesions were unexpectedly high. These findings further support the guideline recommendations of SET as first-line treatment for all patients with intermittent claudication irrespective of level of disease.

Reinterventions after Endovascular Revascularization in Elderly Patients with Critical Limb Ischemia: An Observational Study.

BACKGROUND: Endovascular-first strategy for critical limb ischemia is widely accepted, especially in elderly patients, because of the increasing patency rates and minimally invasive character. Nonetheless, the impact of reinterventions because of endovascular treatment failure in this population is not well known. The aim of this study was to evaluate the reintervention rate and outcomes following reinterventions. METHODS: Patients aged >70 years with critical limb ischemia as a result of aortoiliac, femoropopliteal, and/or crural disease, treated by "endovascular-first strategy" between 2006 and 2013, were retrospectively analyzed. Follow-up was until 31 December 2014. Primary end point was freedom from reintervention or major amputation. Secondary outcome measures were limb salvage and mortality after reintervention. Reintervention was defined as endovascular or surgical re-revascularization and categorized into early reintervention (<3 months) and late reintervention (>3 months). RESULTS: In total, 263 patients were treated by endovascular revascularization. The majority (60%) of the treated lesion was located in the femoropopliteal segment. In total, a reintervention was performed in 32%, with 48% performed within 3 months. Freedom from reintervention or major amputation at 1 and 3 years was 0.71 ± 0.03 and 0.61 ± 0.03, respectively. The 1-year Kaplan-Meier estimate amputation-free survival was 0.35 ± 0.06 in the early reintervention group, compared with 0.73 ± 0.06 in the late reintervention group and 0.71 ± 0.04 in the no reintervention group (P < 0.001; log rank). The 1-year mortality in the early reintervention group was 0.35 ± 0.06, compared with 0.14 ± 0.05 in the late reintervention group and 0.29 ± 0.04 in the group who did not require reintervention (P = 0.047; log rank). CONCLUSIONS: Endovascular revascularization first strategy for critical limb ischemia results in high reintervention rates in elderly patients. Failure of the endovascular revascularization requiring early reintervention is associated with lower amputation-free survival.

Combination of endovascular revascularization and supervised exercise therapy for intermittent claudication: a systematic review and meta-analysis.

BACKGROUND: Peripheral arterial disease is a major health concern in the Western world, often treated with endovascular revascularization (EVR) or supervised exercise therapy (SET). In this systematic review and meta-analysis, we assessed the outcomes after combination treatment of EVR and SET, compared with EVR or SET alone. EVIDENCE ACQUISITION: We performed a systematic search of Embase, Medline, Web of Science, Cochrane Central and Google Scholar. Only randomized controlled trials comparing combination treatment with EVR or SET only, for patients with intermittent claudication due to femoropopliteal or aortoiliac peripheral artery disease, were included. Primary outcome was maximum walking distance (MWD) at 6 and 12 months' follow-up. Secondary outcomes included pain-free walking distance (PFWD), quality of life and adverse events. Pooled estimates of difference in walking distance between EVR plus SET, EVR only and SET only were calculated using random effects models. EVIDENCE SYNTHESIS: Our search yielded 812 articles, of which 7 were finally included in the systematic review. Three studies reported the outcomes of combination treatment versus SET and three more reported the outcomes of combination versus EVR. Follow-up ranged between 6 and 24 months. Combination treatment was associated with a greater MWD at 6 months compared to EVR only or SET only, with a standardized mean difference (SMD) of 0.86 (95% CI: 0.15, 1.57) and 0.41 (95% CI: 0.17, 0.66), respectively. At twelve months no significant difference in maximum walking distance was observed between combination treatment compared to EVR (SMD 0.96 [95% CI: -0.44, 2.37]) or SET (SMD 0.52 [95% CI: -0.17, 1.20]). Compared to EVR only, the combination treatment was associated with a greater PFWD walking distance at 12 months (SMD 0.73 [95% CI 0.01, 1.45]). Most studies reported only minor differences in quality of life in favor of the combination treatment, or no difference at all. CONCLUSIONS: Combination treatment of endovascular revascularization followed by SET shows a greater improvement in maximum walking distance at 6 months' follow-up compared to EVR only or SET only, while this difference was no longer present after 12 months.

Life Expectancy and Outcome of Different Treatment Strategies for Critical Limb Ischemia in the Elderly Patients.

BACKGROUND: The treatment of critical limb ischemia (CLI) in the elderly patients is challenging because of the comorbidity and fragility of these patients. We analyzed survival in relation to different treatment options and estimated life expectancy of our study group by age and gender. METHODS: All patients aged ≥70 years, presenting with chronic CLI, between 2006 and 2013 were included. The treatment was conservative, endovascular, surgical, or by primary major amputation. The interest was in the effect of conservative versus nonconservative treatment on survival. Furthermore, we compared mortality and life expectancy between the study population to the overall Dutch population by age and gender. RESULTS: In total, 686 legs in 651 patients were treated. Initial treatment of patients was conservative (n = 181), endovascular (n = 259), surgical (n = 169), or amputation (n = 42). The overall 1-year mortality was 29%. Patients were stratified by age: 70-79 (n = 350) years and ≥80 (n = 301) years. Higher mortality rate ratios (RR) were found in octogenarians compared with patients aged 70-79 years, in the endovascular (P < 0.001) and surgical (P < 0.001) group. The mortality RRs of conservative relatively to nonconservative treatment was 0.84 (95% confidence interval: 0.65-1.09; P = 0.19), not significantly differing between both age groups (P = 0.74). The mortality RR of 3.72 of our study population to the Dutch general population was high, with an excess mortality of 272%. Life expectancy at the age of 70 years was substantially decreased by 9 and 8 years for, respectively, the male and female population. CONCLUSIONS: Mortality rates in elderly patients with CLI are high, corresponding with a decreased life expectancy, regardless of the type of intervention. Revascularization is associated with high periprocedural mortality, especially in octogenarians. Conservative treatment is noninferior to nonconservative treatment in terms of mortality and should be considered as the treatment in octogenarians with substantial comorbidity.

Mortality after major amputation in elderly patients with critical limb ischemia.

BACKGROUND: Owing to the aging population, the number of elderly patients with critical limb ischemia (CLI) has increased. The consequence of amputation is immense. However, at the moment, information about the mortality after amputation in the elderly vascular patients is unknown. For this reason, this study evaluated mortality rates and patient-related factors associated with mortality after a major amputation in elderly patients with CLI. METHODS: From 2006 to 2013, we included patients aged >70 years who were treated for chronic CLI by primary or secondary major amputation within or after 3 months of initial therapy (revascularization or conservative management). Outcome measurements were mortality after major amputation and factors associated with mortality (age, comorbidity and timing of amputation). RESULTS: In total, 168/651 patients (178 legs; 26%) underwent a major amputation. Patients were stratified by age: 70-80 years (n=86) and >80 years (n=82). Overall mortality after major amputation was 44%, 66% and 85% after 1, 3 and 5 years, respectively. The 6-month and 1-year mortality in patients aged 80 years or older was, respectively, 59% or 63% after a secondary amputation <3 months versus 34% and 44% after a secondary amputation >3 months. Per year of age, the mortality rate increased by 4% (P=0.005). No significant difference in mortality after major amputation was found in the presence of comorbidity or according to Rutherford classification. CONCLUSION: Despite developments in the treatment of CLI by revascularization, amputation rates remain high and are associated with tremendous mortality rates. Secondary amputation after a failed attempt of revascularization causes a higher mortality. Further research concerning timing of amputation and patient-related outcome is needed to evaluate if selected patients might benefit from primary amputation.