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OBJECTIVE: The objective of this study was to examine the short- and midterm outcomes of catheter-directed thrombolysis (CDT) for acute lower limb ischemia (ALI), classes Rutherford 1 and 2, with specific attention to functional outcome. METHODS: This retrospective study included patients with ALI treated with CDT from 2 vascular centers between May 2018 and April 2021. Cases were analyzed in groups according to the Rutherford (1 and 2) classification. The primary endpoint was functional outcome during follow-up, assessed by Rutherford's chronic limb ischemia classification. Functional outcomes over time were analyzed by generalized estimating equations. Kaplan-Meier analysis was used to estimate reintervention, amputation, survival, and reintervention-free survival rates. RESULTS: Two hundred cases were included (Rutherford 1, n = 51; Rutherford 2, n = 149). Total median treatment duration was 27 hours in the Rutherford 1 group and 39 hours in the Rutherford 2 group (P= 0.120). Initial clinical success was high (Rutherford 1, 82% vs Rutherford 2, 89%; P= 0.253). Complications were comparable between the 2 groups: major bleeding 8% vs 10% (P= 0.634), major amputation 4% vs 7% (P= 0.603), and mortality 6% vs 6% (P= 0.967). Median follow-up was 32 months (0-63 months). During follow-up, there was a high number of reinterventions (43%) and amputations (20%) in patients with Rutherford 1 limb ischemia, which was comparable to patients with Rutherford 2 limb ischemia. Fifty-six percent of the patients with Rutherford 1 limb ischemia reaching 2 years of follow-up were asymptomatic, 20% had mild and 16% had moderate to severe claudication. Initial clinical success following CDT and not immediately threatened ischemia at presentation are associated with improved functional outcomes during follow-up (P < 0.001 and P= 0.009, respectively). CONCLUSIONS: In our cohort, CDT was effective in reestablishing arterial flow for not immediately threatened ALI. Patients with Rutherford 1 limb ischemia who receive CDT had a more favorable functional outcome than patients with more severe limb ischemia (Rutherford 2). However, reinterventions were required frequently, and there was a substantial risk of complications. CLINICAL IMPACT: Acute lower limb ischemia (ALI) does not immediately jeopardize limb survival in patients with Rutherford 1 limb ischemia but can induce disabling claudication. In such patients, catheter-directed thrombolysis (CDT) is often performed to improve functional outcome. However, previous reports warned about the complications of CDT, and so far, mid- and long-term functional outcomes have not been reported. This study, in which a large cohort of patients with ALI was included, demonstrates a high technical success of CDT for not immediately threatened ALI with more favorable functional outcomes when compared with those with threatened limbs. Nevertheless, major complications pose a serious risk, and the need for reinterventions in the long term is high.
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OBJECTIVE: Inconsistencies in outcome data of therapeutic strategies for acute lower limb ischaemia (ALI) have hindered the synthesis of findings. A core outcome set (COS) may offer a solution to this problem by defining a minimum set of outcomes that are considered essential to all stakeholders involved. The first step in developing a COS is to review the previously reported outcomes on various treatment strategies for ALI. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from inception to August 2023. REVIEW METHODS: This systematic review was conducted in accordance with the Core Outcome Measures in Effectiveness Trials (COMET) initiative framework, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was pre-registered with PROSPERO (CRD42022320073). Abstracts were independently screened by two authors for full text review. All outcomes and their definitions were extracted from selected papers. Outcomes with different terminologies were then categorised into an agreed outcome term. The list of agreed outcomes was given a standardised outcome domain and core area using a 38 item standardised taxonomy. RESULTS: Of 6 184 articles identified, 176 relevant studies were included, yielding 1 325 verbatim outcomes. After deduplication, 72 unique verbatim outcomes were categorised into five broad outcome domains. Outcomes considered key to the evaluation of treatment of ALI were further categorised as delivery of care (19.4%), vascular outcomes (13.8%), and adverse events (12.5%). The three most frequently reported agreed outcomes were amputation (14.1%), death (12.3%), and general bleeding (11.6%). CONCLUSION: This systematic review provides an overview of currently reported outcomes in the literature of interventions for ALI. After categorisation into agreed outcome terms, 72 outcomes were identified that can be used in the development of a COS.
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OBJECTIVE: Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. METHODS: All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. RESULTS: Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT. CONCLUSION: High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.