Because of a lack of robust evidence, the benefits and risks of percutaneous blood clot removal (the removal of a blood clot via a needle puncture in the skin, known as percutaneous thrombectomy) or ultrasound-accelerated thrombolysis (where ultrasound waves are sent by a specific device into the blood vessel to accelerate the dissolution of a blood clot) for the initial treatment of acute limb ischaemia are unclear.
Future research in this area should focus on the effectiveness of treatment options such as blood clot removal, catheter-directed thrombolysis (drug delivery into the blood clot to dissolve the clot), and open surgery (to remove the clot and improve blood flow), as well as investigating any unwanted effects of these treatments.
What is acute limb ischaemia and how is it treated?
Acute ischaemia is a common condition that affects the limbs. Caused by a sudden and significant reduction of blood flow to the limb, acute limb ischaemia can result in pain, paralysis, pallor, and coldness, and in severe cases, it can lead to amputation.
Standard treatments for the initial management of acute limb ischaemia include open surgery and catheter-directed thrombolysis. Other treatments for the initial management for acute limb ischaemia are percutaneous thrombectomy and ultrasound-accelerated thrombolysis.
What did we want to find out?
We wanted to find out if percutaneous thrombectomy or ultrasound-accelerated thrombolysis are better than catheter-directed thrombolysis or open surgery at improving blood flow and reducing amputation, bleeding, and other risks.
What did we do?
We searched for randomised controlled studies that examined percutaneous thrombectomy or ultrasound-accelerated thrombolysis and compared these with either catheter-directed thrombolysis or open surgery in adults with acute limb ischaemia. In randomised controlled studies, the treatments or tests people receive are decided at random, and these usually give the most reliable evidence about treatment effects. We compared and summarised the results of the identified study and rated our confidence in the evidence, based on factors such as methods and size of the study.
What did we find?
We found one study that involved 60 people with acute limb ischaemia. The study lasted 30 days and compared ultrasound-accelerated thrombolysis with catheter-directed thrombolysis. The study did not present the results in a way that could tell us whether ultrasound-accelerated thrombolysis, compared with catheter-directed thrombolysis, had an effect on blood flow, and it is unclear if these treatments have an effect on amputation, bleeding, and other risks. Thus, we are very uncertain about the results.
What are the limitations of the evidence?
We have very little confidence in the evidence because it is possible that people in the study were aware of what treatment they received. The study did not provide information about important effects of the treatments (blood flow), and the study involved only a small number of people.
How up to date is this evidence?
The evidence is up to date to March 2021.
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.
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.
To assess the safety and effectiveness of percutaneous thrombectomy or ultrasound-accelerated thrombolysis for the initial management of acute limb ischaemia in adults.
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.
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.
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.
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.