Samuel T Araujo1, Daniel H Moreno1, Daniel G Cacione1. 1. Division of Vascular and Endovascular Surgery, Department of Surgery, UNIFESP - Escola Paulista de Medicina, São Paulo, Brazil.
Abstract
BACKGROUND: Acute limb ischaemia (ALI), the sudden and significant reduction of blood flow to the limb, is considered a vascular emergency. In the general population, the incidence is estimated as 14 per 100,000. Prognosis depends on the time it takes to diagnose the condition and begin appropriate treatment. Standard initial interventional treatments include conventional open surgery and endovascular interventions such as catheter-directed thrombolysis (CDT). Percutaneous interventions, such as percutaneous thrombectomy (PT, including mechanical thrombectomy or pharmomechanical thrombectomy) and ultrasound-accelerated thrombolysis (USAT), are also performed as alternative endovascular techniques. The proposed advantages of PT and USAT include reduced time to revascularisation and when combined with catheter-directed thrombolysis, a reduction in dose of thrombolytic agents and infusion time. The benefits of PT or USAT versus open surgery or thrombolysis alone are still uncertain. In this review, we compared PT or USAT against standard treatment for ALI, in an attempt to determine if any technique is comparatively safer and more effective. OBJECTIVES: To assess the safety and effectiveness of percutaneous thrombectomy or ultrasound-accelerated thrombolysis for the initial management of acute limb ischaemia in adults. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov to 3 March 2021. We searched reference lists of relevant studies and papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared PT (any modality, including mechanical thrombectomy (aspiration, rheolysis, rotation) or pharmomechanical thrombectomy) or USAT with open surgery, thrombolysis alone, no treatment, or another PT modality for the treatment of ALI. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed risk of bias, extracted data, performed data analysis, and assessed the certainty of evidence according to GRADE. Outcomes of interest were primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects. MAIN RESULTS: We included one RCT in this review. This study had a total of 60 participants and compared USAT with standard treatment (CDT). The study included 32 participants in the CDT group and 28 participants in the USAT group. We found no evidence of a difference between USAT and CDT alone for the following evaluated outcomes: amputation rate (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.17 to 7.59); major bleeding (RR 1.71, 95% CI 0.31 to 9.53); clinical success (RR 1.00, 95% CI 0.94 to 1.07); and adverse effects (RR 5.69, 95% CI 0.28 to 113.72). We rated the certainty of the evidence as very low for these outcomes. We downgraded the certainty of the evidence for amputation rate, major bleeding, clinical success, and adverse effects by two levels due to serious limitations in the design (there was a high risk of bias in critical domains) and by two further levels due to imprecision (a small number of participants and only one study included). The study authors reported 30-day patency, but did not report primary and secondary patency separately. The patency rate in the successfully lysed participants was 71% (15/21) in the USAT group and 82% (22/27) in the CDT group. The study authors did not directly report secondary patency, which is patency after secondary procedures, but they did report on secondary procedures. Secondary procedures were subdivided into embolectomy and bypass grafting. Embolectomy was performed on 14% (4/28) of participants in the USAT group versus 3% (1/32) of participants in the CDT group. Bypass grafting was performed on 4% (1/28) of participants in the USAT group versus 0% in the CDT group. As we did not have access to the specific participant data, it was not possible to assess these outcomes further. We did not identify studies comparing the other planned interventions. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess the safety and effectiveness of USAT versus CDT alone for ALI for our evaluated outcomes: amputation rate, major bleeding, clinical success, and adverse effects. Primary and secondary patency were not reported separately. There was no RCT evidence for PT. Limitations of this systematic review derive from the single included study, small sample size, short clinical follow-up period, and high risk of bias in critical domains. For this reason, the applicability of the results is limited. There is a need for high-quality studies to compare PT or USAT against open surgery, thrombolysis alone, no treatment, or other PT modalities for ALI. Future trials should assess outcomes, such as primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects.
BACKGROUND: Acute limb ischaemia (ALI), the sudden and significant reduction of blood flow to the limb, is considered a vascular emergency. In the general population, the incidence is estimated as 14 per 100,000. Prognosis depends on the time it takes to diagnose the condition and begin appropriate treatment. Standard initial interventional treatments include conventional open surgery and endovascular interventions such as catheter-directed thrombolysis (CDT). Percutaneous interventions, such as percutaneous thrombectomy (PT, including mechanical thrombectomy or pharmomechanical thrombectomy) and ultrasound-accelerated thrombolysis (USAT), are also performed as alternative endovascular techniques. The proposed advantages of PT and USAT include reduced time to revascularisation and when combined with catheter-directed thrombolysis, a reduction in dose of thrombolytic agents and infusion time. The benefits of PT or USAT versus open surgery or thrombolysis alone are still uncertain. In this review, we compared PT or USAT against standard treatment for ALI, in an attempt to determine if any technique is comparatively safer and more effective. OBJECTIVES: To assess the safety and effectiveness of percutaneous thrombectomy or ultrasound-accelerated thrombolysis for the initial management of acute limb ischaemia in adults. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov to 3 March 2021. We searched reference lists of relevant studies and papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared PT (any modality, including mechanical thrombectomy (aspiration, rheolysis, rotation) or pharmomechanical thrombectomy) or USAT with open surgery, thrombolysis alone, no treatment, or another PT modality for the treatment of ALI. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed risk of bias, extracted data, performed data analysis, and assessed the certainty of evidence according to GRADE. Outcomes of interest were primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects. MAIN RESULTS: We included one RCT in this review. This study had a total of 60 participants and compared USAT with standard treatment (CDT). The study included 32 participants in the CDT group and 28 participants in the USAT group. We found no evidence of a difference between USAT and CDT alone for the following evaluated outcomes: amputation rate (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.17 to 7.59); major bleeding (RR 1.71, 95% CI 0.31 to 9.53); clinical success (RR 1.00, 95% CI 0.94 to 1.07); and adverse effects (RR 5.69, 95% CI 0.28 to 113.72). We rated the certainty of the evidence as very low for these outcomes. We downgraded the certainty of the evidence for amputation rate, major bleeding, clinical success, and adverse effects by two levels due to serious limitations in the design (there was a high risk of bias in critical domains) and by two further levels due to imprecision (a small number of participants and only one study included). The study authors reported 30-day patency, but did not report primary and secondary patency separately. The patency rate in the successfully lysed participants was 71% (15/21) in the USAT group and 82% (22/27) in the CDT group. The study authors did not directly report secondary patency, which is patency after secondary procedures, but they did report on secondary procedures. Secondary procedures were subdivided into embolectomy and bypass grafting. Embolectomy was performed on 14% (4/28) of participants in the USAT group versus 3% (1/32) of participants in the CDT group. Bypass grafting was performed on 4% (1/28) of participants in the USAT group versus 0% in the CDT group. As we did not have access to the specific participant data, it was not possible to assess these outcomes further. We did not identify studies comparing the other planned interventions. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess the safety and effectiveness of USAT versus CDT alone for ALI for our evaluated outcomes: amputation rate, major bleeding, clinical success, and adverse effects. Primary and secondary patency were not reported separately. There was no RCT evidence for PT. Limitations of this systematic review derive from the single included study, small sample size, short clinical follow-up period, and high risk of bias in critical domains. For this reason, the applicability of the results is limited. There is a need for high-quality studies to compare PT or USAT against open surgery, thrombolysis alone, no treatment, or other PT modalities for ALI. Future trials should assess outcomes, such as primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects.
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