Background
Thrombolysis involves dissolving a blood clot by injecting a chemical agent at the site of the clot. It can be used as an alternative to surgery for managing sudden severely reduced blood flow (acute ischaemia) in the leg. A blood clot (thrombosis) can form in a leg blood vessel that shows severe narrowing (stenosis) in a natural artery or a bypass graft, or it can travel into the leg arteries after forming elsewhere, when it is called an embolus. Major complications of thrombolysis are bleeding and stroke.
Study characteristics and key results
Authors of the review identified five controlled trials with a total of 1292 participants who needed immediate care for reduced blood flow in the leg(s) (current until 7 May 2018). Participants were randomly assigned to one of two groups for initial treatment: (1) non-surgical thrombolysis, or (2) surgery. The specific agents used to break up clots (thrombolytic agents) were called recombinant tissue plasminogen activator and urokinase. The included studies provided no clear evidence about which treatment - thrombolysis or surgery - was a better option for preventing limb amputation (limb salvage) and no clear evidence about which treatment was better for preventing death or improving amputation rates within one month, six months, or one year after initial treatment. Evidence for these three outcomes at one month was rated between low and very low quality. No conclusion can be made about which treatment was better for keeping vessels unblocked after treatment (vessel patency) because this outcome was not well reported. More major complications, including bleeding (haemorrhage) and continued ischaemia or blockage (distal embolisation), were reported in the group receiving thrombolysis. There was no difference in the occurrence of stroke at one month between the two treatment groups. Although people receiving initial thrombolysis had increased risk of some complications, they showed greater reduction in the level of intervention required compared with that predicted before intervention. The higher risks of complications with thrombolysis have to be weighted against individual risks in surgery.
Quality of the evidence
The quality of the evidence was generally low. We downgraded the quality owing to risk of bias. Bias is a way to describe how researchers, clinicians, or participants might influence results unintentionally. Blinding is a method used to prevent people involved in the trial from knowing what treatment group a participant was in and reducing measurement bias. None of the studies included in this review used methods to stop participants or researchers or outcome assessors from knowing what treatment they were assigned to. Also, there was uncertainty about the true effect of each treatment type. Results show wide differences in outcome measures (effects) between studies (heterogeneity). For example, following surgical treatment, one-year mortality ranged from 9.8% to 42%. Such a wide range in percentages may indicate that the studies compared were quite different. In addition, both selection criteria (duration of treatment and severity of ischaemia) and method of thrombolysis (agent, dose, and duration) varied between studies, making comparison more difficult.
Conclusion
This review found no evidence of a difference between thrombolysis and surgery for treatment of acute limb ischaemia for our outcomes of interest. Those receiving thrombolysis treatment may be at higher risk of complications such as bleeding. The quality of data generated by the included studies is low.
There is currently no evidence in favour of either initial thrombolysis or initial surgery as the preferred option in terms of limb salvage, amputation, or death at 30 days, six months, or one year. Low-quality evidence suggests that thrombolysis may be associated with higher risk of haemorrhagic complications and ongoing limb ischaemia (distal embolisation). The higher risk of complications must be balanced against risks of surgery in each individual case. Trial results show no statistical difference in stroke, but the confidence interval is very wide, making it difficult to interpret whether this finding is clinically important. We used GRADE criteria to assess the quality of the evidence as generally low. We downgraded quality owing to risk of bias, imprecision, and heterogeneity between included studies.
Both peripheral arterial thrombolysis and surgery can be used in the management of peripheral arterial ischaemia. Much is known about the indications, risks, and benefits of thrombolysis. However, whether thrombolysis works better than surgery for initial management of acute limb ischaemia remains unknown. This is the second update of the review first published in 2002.
To determine whether thrombolysis or surgery is the more effective technique in the initial management of acute limb ischaemia due to thromboembolism.
For this update, the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, CINAHL, AMED, and clinical trials registries up to 7 May 2018.
All randomised controlled studies comparing thrombolysis and surgery for initial treatment of acute limb ischaemia.
We independently assessed trial quality and extracted data. Agreement was reached by consensus. We performed analyses using odds ratios (ORs) and 95% confidence intervals (CIs).
We identified no new studies for this update. We included five trials with a total of 1292 participants; agents used for thrombolysis were recombinant tissue plasminogen activator and urokinase. Trials were generally of moderate methodological quality. The quality of evidence according to GRADE was generally low owing to risk of bias (lack of blinding), imprecision in estimates, and heterogeneity.
Trial results showed no clear differences in limb salvage, amputation, or death at 30 days (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.41 to 2.55, 4 studies, 636 participants; OR 0.97, 95% CI 0.51 to 1.85, 3 studies, 616 participants; OR 0.59, 95% CI 0.31 to 1.14, 4 studies, 636 participants, respectively), and we rated the evidence as low, low, and moderate quality, respectively. Trial results show no clear differences for any of the three outcomes at six months or one year between initial surgery and initial thrombolysis. A single study evaluated vessel patency, so no overall association could be determined (OR 0.46, 95% CI 0.08 to 2.76, 20 participants; very low-quality evidence). Evidence of increased risk of major haemorrhage (OR 3.22, 95% CI 1.79 to 5.78, 4 studies, 1070 participants; low-quality evidence) and distal embolisation (OR 31.68, 95% CI 6.23 to 161.07, 3 studies, 678 participants; very low-quality evidence) was associated with thrombolysis treatment at 30 days, and there was no clear difference in stroke (OR 5.33, 95% CI 0.95 to 30.11, 5 studies, 1180 participants; low-quality evidence). Participants treated by initial thrombolysis had a greater reduction in the level of intervention required, compared with a pre-intervention prediction, at 30 days (OR 9.06, 95% CI 4.95 to 16.56, 2 studies, 502 participants). None of the included studies evaluated time to thrombolysis as an outcome.