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Background: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions., Objectives: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery., Search Methods: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov., Selection Criteria: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach., Main Results: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up., Authors' Conclusions: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Patients who present with problems with definitive dialysis access (arteriovenous fistula (AVF) or arteriovenous graft (AVG)) become catheter dependent (temporary access), a condition that often carries a higher risk of infections, central venous occlusions and recurrent hospitalisations. For AVG, primary patency rates are reported to be 30% to 90% in patients undergoing thrombectomy or thrombolysis. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines, surgery is preferred when the cause of the thrombosis is a stenosis at the site of the anastomosis in thrombosed AVF. The European Best Practice Guidelines (EBPG) reported that thrombosed AVF may be preferably treated with endovascular techniques, but when the cause of thrombosis is in the anastomosis, surgery provides better results with re-anastomosis. Therefore, there is a need to carry out a systematic review to determine the effectiveness and safety of the intervention for thrombosed fistulae., Objectives: This review aims to establish the efficacy and safety of interventions for failed AVF and AVG in patients receiving haemodialysis (HD)., Search Methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 28 January 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Portal (ICTRP) Search Portal and ClinicalTrials.gov., Selection Criteria: The review included randomised controlled trials (RCTs) and quasi-RCTs in people undergoing HD treatment using AVF or AVG presenting with clinical or haemodynamic evidence of thrombosis. Patients had to have used an AVF or AVG at least once., Data Collection and Analysis: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: Our search strategy identified 14 eligible studies (1176 randomised participants) for inclusion in this review. We included three types of interventions for the treatment of thrombosed AVF and AVG: (1) types of thrombectomy, (2) types of thrombolysis and (3) surgical procedures. Most of the included studies had a high risk of bias due to a poor study design, a low number of patients and industry involvement. Overall, there was insufficient evidence to suggest that a specific intervention was better than another for the outcomes of failure, primary patency at 30 days, technical success and adverse events (both major and minor). Primary patency at 30 days may improve with surgical compared to mechanical thrombectomy (3 studies, 404 participants: RR 1.36, 95% CI 1.07 to 1.67); however, the evidence is very uncertain. Death, access dysfunction, successful dialysis, and SONG (Standards Outcomes in Nephrology) outcomes were rarely reported. The current review is limited by the small number of available studies with a limited number of patients enrolled. Most of the studies included in this review have a high risk of bias and a low or very low certainty of evidence. Further research is required to define the most effective and clinically appropriate technique for access dysfunction., Authors' Conclusions: It remains unclear whether any intervention therapy affects the patency at 30 days or failure in any thrombosed HD AV access (very low certainty of evidence). Future research will very likely change the evidence base. Based on the importance of HD access to these patients, future studies of these interventions among people receiving HD should be a priority., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people and the third most common cause of mortality in surgical patients. People undergoing bariatric surgery have the additional risk factor of being overweight. Although VTE prophylaxis in surgical patients is well established, the best way to prevent VTE in those undergoing bariatric surgery is less clear., Objectives: To evaluate the benefits and harms of pharmacological interventions (alone or in combination) on venous thromboembolism and other health outcomes in people undergoing bariatric surgery compared to the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention or started at a different time point, another pharmacological intervention, no intervention or placebo., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 1 November 2021., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs in males and females of any age undergoing bariatric surgery comparing pharmacological interventions for VTE (alone or in combination) with the same pharmacological intervention administered at a different dose or frequency, the same pharmacological intervention started at a different time point, a different pharmacological intervention, no treatment or placebo., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were 1. VTE and 2. major bleeding. Our secondary outcomes were 1. all-cause mortality, 2. VTE-related mortality, 3. PE, 4. DVT, 5. adverse effects and 6. quality of life. We used GRADE to assess certainty of evidence for each outcome., Main Results: We included seven RCTs with 1045 participants. Data for meta-analysis were available from all participants. Four RCTs (597 participants) compared higher-dose heparin to standard-dose heparin: one of these studies (139 participants) used unfractionated heparin (UFH) and the other three (458 participants) used low-molecular-weight heparin (LMWH). One study compared heparin versus pentasaccharide (198 participants), and one study compared starting heparin before versus after bariatric surgery (100 participants). One study (150 participants) compared combined mechanical and pharmacological (enoxaparin) prophylaxis versus mechanical prophylaxis alone. The duration of the interventions ranged from seven to 15 days, and follow-up ranged from 10 to 180 days. Higher-dose heparin versus standard-dose heparin Compared to standard-dose heparin, higher-dose heparin may result in little or no difference in the risk of VTE (RR 0.55, 95% CI 0.05 to 5.99; 4 studies, 597 participants) or major bleeding (RR 1.19, 95% CI 0.48 to 2.96; I 2 = 8%; 4 studies, 597 participants; low-certainty) in people undergoing bariatric surgery. The evidence on all-cause mortality, VTE-related mortality, PE, DVT and adverse events (thrombocytopenia) is uncertain (effect not estimable or very low-certainty evidence). Heparin versus pentasaccharide Heparin compared to a pentasaccharide after bariatric surgery may result in little or no difference in the risk of VTE (RR 0.83, 95% CI 0.19 to 3.61; 1 study, 175 participants) or DVT (RR 0.83, 95% CI 0.19 to 3.61; 1 study, 175 participants). The evidence on major bleeding, PE and mortality is uncertain (effect not estimable or very low-certainty evidence). Heparin started before versus after the surgical procedure Starting prophylaxis with heparin 12 hours before surgery versus after surgery may result in little or no difference in the risk of VTE (RR 0.11, 95% CI 0.01 to 2.01; 1 study, 100 participants) or DVT (RR 0.11, 95% CI 0.01 to 2.01; 1 study, 100 participants). The evidence on major bleeding, all-cause mortality and VTE-related mortality is uncertain (effect not estimable or very low-certainty evidence). We were unable to assess the effect of this intervention on PE or adverse effects, as the study did not measure these outcomes. Combined mechanical and pharmacological prophylaxis versus mechanical prophylaxis alone Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery compared to mechanical prophylaxis alone (RR 0.05, 95% CI 0.00 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 9; 1 study, 150 participants; low-certainty). We were unable to assess the effect of this intervention on major bleeding or morality (effect not estimable), or on PE or adverse events (not measured). No studies measured quality of life., Authors' Conclusions: Higher-dose heparin may make little or no difference to venous thromboembolism or major bleeding in people undergoing bariatric surgery when compared to standard-dose heparin. Heparin may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to pentasaccharide. There are inadequate data to draw conclusions about the effects of heparin compared to pentasaccharide on major bleeding. Starting prophylaxis with heparin 12 hours before bariatric surgery may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to starting heparin after bariatric surgery. There are inadequate data to draw conclusions about the effects of heparin started before versus after surgery on major bleeding. Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery when compared to mechanical prophylaxis alone. No data are available relating to major bleeding. The certainty of the evidence is limited by small sample sizes, few or no events, and risk of bias concerns. Future trials must be sufficiently large to enable analysis of relevant clinical outcomes, and should standardise the time of treatment and follow-up. They should also address the effect of direct oral anticoagulants and antiplatelets, preferably grouping them according to the type of intervention., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Antiplatelet agents may be useful for the treatment of deep venous thrombosis (DVT) when used in addition to best medical practice (BMP), which includes anticoagulation, compression stockings, and clinical care such as physical exercise, skin hydration, etc. Antiplatelet agents could minimise complications such as post-thrombotic syndrome (PTS) and pulmonary embolism (PE). They may also reduce the recurrence of the disease (recurrent venous thromboembolism (recurrent VTE)). However, antiplatelet agents may increase the likelihood of bleeding events., Objectives: To assess the effects of antiplatelet agents in addition to current BMP compared to current BMP (with or without placebo) for the treatment of DVT., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 December 2021. The review authors searched LILACS and IBECS databases (15 December 2021) and also checked the bibliographies of included trials for further references to relevant trials, and contacted specialists in the field, manufacturers and authors of the included trials., Selection Criteria: We considered randomised controlled trials (RCTs) examining antiplatelet agents compared to BMP following initial standard anticoagulation treatment for DVT. We included studies where antiplatelet agents were given in addition to current BMP compared to current BMP (with or without placebo) for the treatment of DVT (acute: treatment started within 21 days of symptom onset; chronic: treatment started after 21 days of symptom onset). We evaluated only RCTs where the antiplatelet agents were the unique difference between the groups (intervention and control)., Data Collection and Analysis: We used standard Cochrane methodological procedures. Two review authors independently extracted data and assessed risk of bias of the trials. Any disagreements were resolved by discussion with a third review author. We calculated outcome effects using risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) and the number needed to treat to benefit (NNTB)., Main Results: We included six studies with 1625 eligible participants, with data up to 37.2 months of follow-up. For one preplanned comparison (i.e. antiplatelet agents plus BMP versus BMP plus placebo) for acute DVT we identified no eligible studies for inclusion. In acute DVT, antiplatelet agents plus BMP versus BMP alone was assessed by one study (500 participants), which reported on four outcomes until 6 months of follow-up. There were no deaths and no cases of major bleeding reported. The participants who received antiplatelet agents showed a lower risk of PTS (RR 0.74, 95% CI 0.61 to 0.91; 1 study, 500 participants; very low-certainty evidence). The control group presented a lower risk of adverse events compared to the intervention group (RR 2.88, 95% CI 1.06 to 7.80; 1 study, 500 participants; very low-certainty evidence). This study did not provide information for recurrent VTE or PE. In chronic DVT, antiplatelet agents plus BMP versus BMP alone was assessed by one study (224 participants). The study authors reported four relevant outcomes, three of which (major bleeding, mortality and adverse events) showed no events during the 3 years of follow-up. Therefore, an effect estimate could only be reported for recurrent VTE, favouring antiplatelet agents plus BMP versus BMP alone (RR 0.12, 95% CI 0.05 to 0.34; 1 study, 224 participants; very low-certainty evidence). For the outcomes PE and PTS, this study did not present information which could be used for analysis. In chronic DVT, antiplatelet agents plus BMP versus BMP plus placebo was assessed by four studies (901 participants). The meta-analysis of this pooled data showed a lower risk of recurrent VTE for the antiplatelet agents group (RR 0.65, 95%, CI 0.43 to 0.96; NNTB = 14; low-certainty evidence). For major bleeding, we found no clear difference between placebo and intervention groups until 37.2 months of follow-up (RR 0.98, 95% CI 0.29 to 3.34; 1 study, 583 participants; moderate-certainty evidence). In PE fatal/non-fatal outcome, we found no clear difference with the use of antiplatelet agents (RR 0.52, 95% CI 0.23 to 1.14; 1 study, 583 participants; moderate-certainty evidence). For all-cause mortality, the overall effect of antiplatelet agents did not differ from the placebo group (RR 0.48, 95% CI 0.21 to 1.06; 3 studies, 649 participants; moderate-certainty evidence). The adverse events outcome did not show a clear difference (RR 1.57, 95% CI 0.34 to 7.19; 2 studies, 621 participants; moderate-certainty evidence). There is no assessment of PTS in these studies. We downgraded the certainty of evidence for risk of bias, indirectness, imprecision and publication bias., Authors' Conclusions: In chronic DVT settings, following the initial standard treatment with anticoagulants, there is low-certainty evidence that antiplatelet agents in addition to BMP may reduce recurrent VTE, (NNTB = 14) when compared to BMP plus placebo. Moderate-certainty evidence shows no clear difference in adverse events, major bleeding and PE when antiplatelet agents are used in addition to BMP compared to BMP plus placebo. In acute and chronic DVT settings, following the initial standard treatment with anticoagulants, we can draw no conclusions for antiplatelet agents in addition to BMP compared to BMP alone due to very low-certainty evidence.  Trials of high methodological quality, that are large and of sufficient duration to detect significant clinical outcomes are needed. Trials should ideally last more than 4 years in order to estimate the long-term effect of antiplatelet agents. Trials should include people with acute and chronic DVT and provide relevant individual data, such as the outcome for each index event (DVT or PE), the use of an inferior vena cava (IVC) filter, whether the DVT is provoked or unprovoked, and the age of participants., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Carotid artery stenosis is an important cause of stroke and transient ischemic attack. Correctly and rapidly identifying patients with symptomatic carotid artery stenosis is essential for adequate treatment with early cerebral revascularization. Doubts about the diagnostic value regarding the accuracy of duplex ultrasound (DUS) and the possibility of using DUS as the single diagnostic test before carotid revascularization are still debated., Objectives: To estimate the accuracy of DUS in individuals with symptomatic carotid stenosis verified by either digital subtraction angiography (DSA), computed tomography angiography (CTA), or magnetic resonance angiography (MRA)., Search Methods: We searched CRDTAS, CENTRAL, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science, HTA, DARE, and LILACS up to 15 February 2021. We handsearched the reference lists of all included studies and other relevant publications and contacted experts in the field to identify additional studies or unpublished data., Selection Criteria: We included studies assessing DUS accuracy against an acceptable reference standard (DSA, MRA, or CTA) in symptomatic patients. We considered the classification of carotid stenosis with DUS defined with validated duplex velocity criteria, and the NASCET criteria for carotid stenosis measures on DSA, MRA, and CTA. We excluded studies that included < 70% of symptomatic patients; the time between the index test and the reference standard was longer than four weeks or not described, or that presented no objective criteria to estimate carotid stenosis., Data Collection and Analysis: The review authors independently screened articles, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-2 domain list. We extracted data with an effort to complete a 2 × 2 table (true positives, true negatives, false positives, and false negatives) for each of the different categories of carotid stenosis and reference standards. We produced forest plots and summary receiver operating characteristic (ROC) plots to summarize the data. Where meta-analysis was possible, we used a bivariate meta-analysis model., Main Results: We identified 25,087 unique studies, of which 22 were deemed eligible for inclusion (4957 carotid arteries). The risk of bias varied considerably across the studies, and studies were generally of moderate to low quality. We narratively described the results without meta-analysis in seven studies in which the criteria used to determine stenosis were too different from the duplex velocity criteria proposed in our protocol or studies that provided insufficient data to complete a 2 × 2 table for at least in one category of stenosis. Nine studies (2770 carotid arteries) presented DUS versus DSA results for 70% to 99% carotid artery stenosis, and two (685 carotid arteries) presented results from DUS versus CTA in this category. Seven studies presented results for occlusion with DSA as the reference standard and three with CTA as the reference standard. Five studies compared DUS versus DSA for 50% to 99% carotid artery stenosis. Only one study presented results from 50% to 69% carotid artery stenosis. For DUS versus DSA, for < 50% carotid artery stenosis, the summary sensitivity was 0.63 (95% confidence interval [CI] 0.48 to 0.76) and the summary specificity was 0.99 (95% CI 0.96 to 0.99); for the 50% to 69% range, only one study was included and meta-analysis not performed; for the 50% to 99% range, the summary sensitivity was 0.97 (95% CI 0.95 to 0.98) and the summary specificity was 0.70 (95% CI 0.67 to 0.73); for the 70% to 99% range, the summary sensitivity was 0.85 (95% CI 0.77 to 0.91) and the summary specificity was 0.98 (95% CI 0.74 to 0.90); for occlusion, the summary sensitivity was 0.91 (95% CI 0.81 to 0.97) and the summary specificity was 0.95 (95% CI 0.76 to 0.99). For sensitivity analyses, excluding studies in which participants were selected based on the presence of occlusion on DUS had an impact on specificity: 0.98 (95% CI 0.97 to 0.99). For DUS versus CTA, we found two studies in the range of 70% to 99%; the sensitivity varied from 0.57 to 0.94 and the specificity varied from 0.87 to 0.98. For occlusion, the summary sensitivity was 0.95 (95% CI 0.80 to 0.99) and the summary specificity was 0.91 (95% CI 0.09 to 0.99). For DUS versus MRA, there was one study with results for 50% to 99% carotid artery stenosis, with a sensitivity of 0.88 (95% CI 0.70 to 0.98) and specificity of 0.60 (95% CI 0.15 to 0.95); in the 70% to 99% range, two studies were included, with sensitivity that varied from 0.54 to 0.99 and specificity that varied from 0.78 to 0.89. We could perform only a few of the proposed sensitivity analyses because of the small number of studies included., Authors' Conclusions: This review provides evidence that the diagnostic accuracy of DUS is high, especially at discriminating between the presence or absence of significant carotid artery stenosis (< 50% or 50% to 99%). This evidence, plus its less invasive nature, supports the early use of DUS for the detection of carotid artery stenosis. The accuracy for 70% to 99% carotid artery stenosis and occlusion is high. Clinicians should exercise caution when using DUS as the single preoperative diagnostic method, and the limitations should be considered. There was little evidence of the accuracy of DUS when compared with CTA or MRA. The results of this review should be interpreted with caution because they are based on studies of low methodological quality, mainly due to the patient selection method. Methodological problems in participant inclusion criteria from the studies discussed above apparently influenced an overestimated estimate of prevalence values. Most of the studies included failed to precisely describe inclusion criteria and previous testing. Future diagnostic accuracy studies should include direct comparisons of the various modalities of diagnostic tests (mainly DUS, CTA, and MRA) for carotid artery stenosis since DSA is no longer considered to be the best method for diagnosing carotid stenosis and less invasive tests are now used as reference standards in clinical practice. Also, for future studies, the participant inclusion criteria require careful attention., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is characterised by oedema, pigmentation, eczema, lipodermatosclerosis, atrophie blanche, and healed or active venous ulcers. Injection sclerotherapy (liquid or foam) is widely used for treatment of varicose veins aiming to transform the varicose veins into a fibrous cord. However, there is limited evidence regarding its effectiveness and safety, especially in patients with more severe disease. This is the second update of the review first published in 2002., Objectives: To assess the effectiveness and safety of injection sclerotherapy for the treatment of varicose veins., Search Methods: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, and LILACS databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 20 July 2021., Selection Criteria: We included all randomised controlled trials (RCTs) (including cluster-randomised trials and first phase cross-over studies) that used injection sclerotherapy for the treatment of varicose veins., Data Collection and Analysis: Two review authors independently assessed, selected and extracted data. Disagreements were cross-checked by a third review author. We used Cochrane's Risk of bias tool to assess the risk of bias. The outcomes of interest were cosmetic appearance, complications, residual varicose veins, quality of life (QoL), persistence of symptoms, and recurrent varicose veins. We calculated risk ratios (RRs) or mean difference (MD) with 95% confidence intervals (CIs). We used the worst-case-scenario for dichotomous data imputation for intention-to-treat analyses. For continuous outcomes, we used the 'last-observation-carried-forward' for data imputation if there was balanced loss to follow-up. We assessed the certainty of the evidence using the GRADE approach., Main Results: We included 23 new RCTs for this update, bringing the total to 28 studies involving 4278 participants. The studies differed in their design, and in which sclerotherapy method, agent or concentration was used. None of the included RCTs compared sclerotherapy to no intervention or to any pharmacological therapy. The certainty of the evidence was downgraded for risk of bias, low number of studies providing information for each outcome, low number of participants, clinical differences between the study participants, and wide CIs. Sclerotherapy versus placebo Foam sclerotherapy may improve cosmetic appearance as measured by IPR-V (independent photography review - visible varicose veins scores) compared to placebo (polidocanol 1%: mean difference (MD) -0.76, 95% CI -0.91 to -0.60; 2 studies, 223 participants; very low-certainty evidence); however, deep vein thrombosis (DVT) rates may be slightly increased in this intervention group (RR 5.10, 95% CI 1.30 to 20.01; 3 studies, 302 participants; very low-certainty evidence). Residual varicose vein rates may be decreased following polidocanol 1% compared to placebo (RR 0.19, 95% CI 0.13 to 0.29; 2 studies, 225 participants; very low-certainty evidence). Following polidocanol 1% use, there may be a possible improvement in QoL as assessed using the VEINES-QOL/Sym questionnaire (MD 12.41, 95% CI 9.56 to 15.26; 3 studies, 299 participants; very low-certainty evidence), and possible improvement in varicose vein symptoms as assessed using the Venous Clinical Severity Score (VCSS) (MD -3.25, 95% CI -3.90 to -2.60; 2 studies, 223 participants; low-certainty evidence). Recurrent varicose veins were not reported for this comparison. Foam sclerotherapy versus foam sclerotherapy with different concentrations Three individual RCTs reported no evidence of a difference in cosmetic appearance after comparing different concentrations of the intervention; data could not be pooled for two of the three studies (RR 1.11, 95% CI 0.84 to 1.47; 1 study, 80 participants; very low-certainty evidence). Similarly, there was no clear difference in rates of thromboembolic complications when comparing one foam concentration with another (RR 1.47, 95% CI 0.41 to 5.33; 3 studies, 371 participants; very low-certainty evidence). Three RCTs investigating higher concentrations of polidocanol foam indicated the rate of residual varicose veins may be slightly decreased in the polidocanol 3% foam group compared to 1% (RR 0.67, 95% CI 0.43 to 1.04; 3 studies, 371 participants; moderate-certainty evidence). No clear improvement in QoL was detected. Two RCTs reported improved VCSS scores with increasing concentrations of foam. Persistence of symptoms were not reported for this comparison. There was no clear difference in recurrent varicose vein rates (RR 0.91, 95% CI 0.62 to 1.32; 1 study, 148 participants; low-certainty evidence). Foam sclerotherapy versus liquid sclerotherapy One RCT reported on cosmetic appearance with no evidence of a difference between foam or liquid sclerotherapy (patient satisfaction scale MD 0.2, 95% CI -0.27 to 0.67; 1 study, 126 participants; very low-certainty evidence). None of the RCTs investigated thromboembolic complications, QoL or persistence of symptoms. Six studies individually showed there may be a benefit to polidocanol 3% foam over liquid sclerotherapy in reducing residual varicose vein rate; pooling data from two studies showed a RR of 0.51, with 95% CI 0.41 to 0.65; 203 participants; very low-certainty evidence. One study reported no clear difference in recurrent varicose vein rates when comparing sodium tetradecyl sulphate (STS) foam or liquid (RR 1.10, 95% CI 0.86 to 1.42; 1 study, 286 participants; very low-certainty evidence). Sclerotherapy versus sclerotherapy with different substances Four RCTs compared sclerotherapy versus sclerotherapy with any other substance. We were unable to combine the data due to heterogeneity or assess the certainty of the evidence due to insufficient data., Authors' Conclusions: There is a very low to low-certainty evidence that, compared to placebo, sclerotherapy is an effective and safe treatment for varicose veins concerning cosmetic appearance, residual varicose veins, QoL, and persistence of symptoms. Rates of DVT may be slightly increased and there were no data concerning recurrent varicose veins. There was limited or no evidence for one concentration of foam compared to another; foam compared to liquid sclerotherapy; foam compared to any other substance; or one technique compared to another. There is a need for high-quality trials using standardised sclerosant doses, with clearly defined core outcome sets, and measurement time points to increase the certainty of the evidence., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Telangiectasias (spider veins) and reticular veins on the lower limbs are very common, increase with age, and have been found in 41% of women. The cause is unknown and the patients may be asymptomatic or can report pain, burning or itching. Treatments include sclerotherapy, laser, intense pulsed light, microphlebectomy and thermoablation, but none is established as preferable., Objectives: To assess the effects of sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy treatments for telangiectasias and reticular veins., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 16 March 2021. We undertook additional searches in LILACS and IBECS databases, reference checking, and contacted specialists in the field, manufacturers and study authors to identify additional studies., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs that compared treatment methods such as sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy for telangiectasias and reticular veins in the lower limb. We included studies that compared individual treatment methods against placebo, or that compared different sclerosing agents, foam or laser treatment, or that used a combination of treatment methods., Data Collection and Analysis: Three review authors independently performed study selection, extracted data, assessed risks of bias and assessed the certainty of evidence using GRADE. The outcomes of interest were resolution or improvement (or both) of telangiectasias, adverse events (including hyperpigmentation, matting), pain, recurrence, time to resolution, and quality of life., Main Results: We included 3632 participants from 35 RCTs. Studies compared a variety of sclerosing agents, laser treatment and compression. No studies investigated intensive pulsed light, thermocoagulation or microphlebectomy. None of the included studies assessed recurrence or time to resolution. Overall the risk of bias of the included studies was moderate. We downgraded the certainty of evidence to moderate or low because of clinical heterogeneity and imprecision due to the wide confidence intervals (CIs) and few participants for each comparison. Any sclerosing agent versus placebo There was moderate-certainty evidence that sclerosing agents showed more resolution or improvement of telangiectasias compared to placebo (standard mean difference (SMD) 3.08, 95% CI 2.68 to 3.48; 4 studies, 613 participants/procedures), and more frequent adverse events: hyperpigmentation (risk ratio (RR) 11.88, 95% CI 4.54 to 31.09; 3 studies, 528 participants/procedures); matting (RR 4.06, 95% CI 1.28 to 12.84; 3 studies, 528 participants/procedures). There may be more pain experienced in the sclerosing-agents group compared to placebo (SMD 0.70, 95% CI 0.06 to 1.34; 1 study, 40 participants; low-certainty evidence). Polidocanol versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.01, 95% CI -0.13 to 0.14; 7 studies, 852 participants/procedures), hyperpigmentation (RR 0.94, 95% CI 0.62 to 1.43; 6 studies, 819 participants/procedures), or matting (RR 0.82, 95% CI 0.52 to 1.27; 7 studies, 859 participants/procedures), but there were fewer cases of pain (SMD -0.26, 95% CI -0.44 to -0.08; 5 studies, 480 participants/procedures) in the polidocanol group. All moderate-certainty evidence. Sodium tetradecyl sulphate (STS) versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD -0.07, 95% CI -0.25 to 0.11; 4 studies, 473 participants/procedures). There was more hyperpigmentation (RR 1.71, 95% CI 1.10 to 2.64; 4 studies, 478 participants/procedures), matting (RR 2.10, 95% CI 1.14 to 3.85; 2 studies, 323 participants/procedures) and probably more pain (RR 1.49, 95% CI 0.99 to 2.25; 4 studies, 409 participants/procedures). All moderate-certainty evidence. Foam versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.04, 95% CI -0.26 to 0.34; 2 studies, 187 participants/procedures); hyperpigmentation (RR 2.12, 95% CI 0.44 to 10.23; 2 studies, 187 participants/procedures) or pain (SMD -0.10, 95% CI -0.44 to 0.24; 1 study, 147 participants/procedures). There may be more matting using foam (RR 6.12, 95% CI 1.04 to 35.98; 2 studies, 187 participants/procedures). All low-certainty evidence. Laser versus any sclerosing agent There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD -0.09, 95% CI -0.25 to 0.07; 5 studies, 593 participants/procedures), or matting (RR 1.00, 95% CI 0.46 to 2.19; 2 studies, 162 participants/procedures), and maybe less hyperpigmentation (RR 0.57, 95% CI 0.40 to 0.80; 4 studies, 262 participants/procedures) in the laser group. All moderate-certainty evidence. High heterogeneity of the studies reporting on pain prevented pooling, and results were inconsistent (low-certainty evidence). Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol) Low-certainty evidence suggests there may be more resolution or improvement (or both) of telangiectasias in the combined group (SMD 5.68, 95% CI 5.14 to 6.23; 2 studies, 710 participants), and no clear difference in hyperpigmentation (RR 0.83, 95% CI 0.35 to 1.99; 2 studies, 656 participants) or matting (RR 0.83, 95% CI 0.21 to 3.28; 2 studies, 656 participants). There may be more pain in the combined group (RR 2.44, 95% CI 1.69 to 3.55; 1 study, 596 participants; low-certainty evidence)., Authors' Conclusions: Small numbers of studies and participants in each comparison limited our confidence in the evidence. Sclerosing agents were more effective than placebo for resolution or improvement of telangiectasias but also caused more adverse events (moderate-certainty evidence), and may result in more pain (low-certainty evidence). There was no evidence of a benefit in resolution or improvement for any sclerosant compared to another or to laser. There may be more resolution or improvement of telangiectasias in the combined laser and polidocanol group compared to polidocanol alone (low-certainty evidence). There may be differences between treatments in adverse events and pain. Compared to other sclerosing agents polidocanol probably causes less pain; STS resulted in more hyperpigmentation, matting and probably pain; foam may cause more matting (low-certainty evidence); laser treatment may result in less hyperpigmentation (moderate-certainty evidence). Further well-designed studies are required to provide evidence for other available treatments and important outcomes (such as recurrence, time to resolution and delayed adverse events); and to improve our confidence in the identified comparisons., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Arterial vascular access is a frequently performed procedure, with a high possibility for adverse events (e.g. pneumothorax, haemothorax, haematoma, amputation, death), and additional techniques such as ultrasound may be useful for improving outcomes. However, ultrasound guidance for arterial access in adults is still under debate., Objectives: To assess the effects of ultrasound guidance for arterial (other than femoral) catheterisation in adults., Search Methods: We searched CENTRAL, MEDLINE, Embase, LILACS, and CINAHL on 21 May 2021. We also searched IBECS, WHO ICTRP, and ClinicalTrials.gov on 16 June 2021, and we checked the reference lists of retrieved articles., Selection Criteria: Randomised controlled trials (RCTs), including cross-over trials and cluster-RCTs, comparing ultrasound guidance, alone or associated with other forms of guidance, versus other interventions or palpation and landmarks for arterial (other than femoral) guidance in adults., Data Collection and Analysis: Two review authors independently performed study selection, extracted data, assessed risk of bias, and assessed the certainty of evidence using GRADE., Main Results: We included 48 studies (7997 participants) that tested palpation and landmarks, Doppler auditory ultrasound assistance (DUA), direct ultrasound guidance with B-mode, or any other modified ultrasound technique for arterial (axillary, dorsalis pedis, and radial) catheterisation in adults. Radial artery Real-time B-mode ultrasound versus palpation and landmarks Real-time B-mode ultrasound guidance may improve first attempt success rate (risk ratio (RR) 1.44, 95% confidence interval (CI) 1.29 to 1.61; 4708 participants, 27 studies; low-certainty evidence) and overall success rate (RR 1.11, 95% CI 1.06 to 1.16; 4955 participants, 28 studies; low-certainty evidence), and may decrease time needed for a successful procedure (mean difference (MD) -0.33 minutes, 95% CI -0.54 to -0.13; 4902 participants, 26 studies; low-certainty evidence) up to one hour compared to palpation and landmarks. Real-time B-mode ultrasound guidance probably decreases major haematomas (RR 0.35, 95% CI 0.23 to 0.56; 2504 participants, 16 studies; moderate-certainty evidence). It is uncertain whether real-time B-mode ultrasound guidance has any effect on pseudoaneurysm, pain, and quality of life (QoL) compared to palpation and landmarks (very low-certainty evidence). Real-time B-mode ultrasound versus DUA One study (493 participants) showed that real-time B-mode ultrasound guidance probably improves first attempt success rate (RR 1.35, 95% CI 1.11 to 1.64; moderate-certainty evidence) and time needed for a successful procedure (MD -1.57 minutes, 95% CI -1.78 to -1.36; moderate-certainty evidence) up to 72 hours compared to DUA. Real-time B-mode ultrasound guidance may improve overall success rate (RR 1.13, 95% CI 0.99 to 1.29; low-certainty evidence) up to 72 hours compared to DUA. Pseudoaneurysm, major haematomas, pain, and QoL were not reported. Real-time B-mode ultrasound versus modified real-time B-mode ultrasound Real-time B-mode ultrasound guidance may decrease first attempt success rate (RR 0.68, 95% CI 0.55 to 0.84; 153 participants, 2 studies; low-certainty evidence), may decrease overall success rate (RR 0.93, 95% CI 0.86 to 1.01; 153 participants, 2 studies; low-certainty evidence), and may lead to no difference in time needed for a successful procedure (MD 0.04 minutes, 95% CI -0.01 to 0.09; 153 participants, 2 studies; low-certainty evidence) up to one hour compared to modified real-time B-mode ultrasound guidance. It is uncertain whether real-time B-mode ultrasound guidance has any effect on major haematomas compared to modified real-time B-mode ultrasound (very low-certainty evidence). Pseudoaneurysm, pain, and QoL were not reported. In-plane versus out-of-plane B-mode ultrasound In-plane real-time B-mode ultrasound guidance may lead to no difference in overall success rate (RR 1.00, 95% CI 0.96 to 1.05; 1051 participants, 8 studies; low-certainty evidence) and in time needed for a successful procedure (MD -0.06 minutes, 95% CI -0.16 to 0.05; 1134 participants, 9 studies; low-certainty evidence) compared to out-of-plane B-mode ultrasound up to one hour. It is uncertain whether in-plane real-time B-mode ultrasound guidance has any effect on first attempt success rate or major haematomas compared to out-of-plane B-mode ultrasound (very low-certainty evidence). Pseudoaneurysm, pain, and QoL were not reported. DUA versus palpation and landmarks DUA may lead to no difference in first attempt success rate (RR 1.01, 95% CI 0.90 to 1.14; 666 participants, 2 studies; low-certainty evidence) or overall success rate (RR 0.99, 95% CI 0.92 to 1.07; 666 participants, 2 studies; low-certainty evidence) and probably increases time needed for a successful procedure (MD 0.45 minutes, 95% CI 0.20 to 0.70; 500 participants, 1 study; moderate-certainty evidence) up to 72 hours compared to palpation and landmarks. Pseudoaneurysm, major haematomas, pain, and QoL were not reported. Oblique-axis versus long-axis in-plane B-mode ultrasound Oblique-axis in-plane B-mode ultrasound guidance may increase overall success rate (RR 1.27, 95% CI 1.05 to 1.53; 215 participants, 2 studies; low-certainty evidence) up to 72 hours compared to long-axis in-plane B-mode ultrasound. It is uncertain whether oblique-axis in-plane B-mode ultrasound guidance has any effect on first attempt success rate, time needed for a successful procedure, and major haematomas compared to long-axis in-plane B-mode ultrasound. Pseudoaneurysm, pain, and QoL were not reported. We are uncertain about effects in the following comparisons due to very low-certainty evidence and unreported outcomes: real-time B-mode ultrasound versus palpation and landmarks (axillary and dorsalis pedis arteries), real-time B-mode ultrasound versus near-infrared laser (radial artery), and dynamic versus static out-of-plane B-mode ultrasound (radial artery)., Authors' Conclusions: Real-time B-mode ultrasound guidance may improve first attempt success rate, overall success rate, and time needed for a successful procedure for radial artery catheterisation compared to palpation, or DUA. In addition, real-time B-mode ultrasound guidance probably decreases major haematomas compared to palpation. However, we are uncertain about the evidence on major haematomas and pain for other comparisons due to very low-certainty evidence and unreported outcomes. We are also uncertain about the effects on pseudoaneurysm and QoL for axillary and dorsalis pedis arteries catheterisation. Given that first attempt success rate and pseudoaneurysm are the most relevant outcomes for people who underwent arterial catheterisation, future studies must measure both. Future trials must be large enough to detect effects, use validated scales, and report longer-term follow-up., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Unruptured intracranial aneurysms are relatively common lesions in the general population, with a prevalence of 3.2%, and are being diagnosed with greater frequency as non-invasive techniques for imaging of intracranial vessels have become increasingly available and used. If not treated, an intracranial aneurysm can be catastrophic. Morbidity and mortality in aneurysmal subarachnoid hemorrhage are substantial: in people with subarachnoid hemorrhage, 12% die immediately, more than 30% die within one month, 25% to 50% die within six months, and 30% of survivors remain dependent. However, most intracranial aneurysms do not bleed, and the best treatment approach is still a matter of debate., Objectives: To assess the risks and benefits of interventions for people with unruptured intracranial aneurysms., Search Methods: We searched CENTRAL (Cochrane Library 2020, Issue 5), MEDLINE Ovid, Embase Ovid, and Latin American and Caribbean Health Science Information database (LILACS). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception to 25 May 2020. There were no language restrictions. We contacted experts in the field to identify further studies and unpublished trials., Selection Criteria: Unconfounded, truly randomized trials comparing conservative treatment versus interventional treatments (microsurgical clipping or endovascular coiling) and microsurgical clipping versus endovascular coiling for individuals with unruptured intracranial aneurysms., Data Collection and Analysis: Two review authors independently selected trials for inclusion according to the above criteria, assessed trial quality and risk of bias, performed data extraction, and applied the GRADE approach to the evidence. We used an intention-to-treat analysis strategy., Main Results: We included two trials in the review: one prospective randomized trial involving 80 participants that compared conservative treatment to endovascular coiling, and one randomized controlled trial involving 136 participants that compared microsurgical clipping to endovascular coiling for unruptured intracranial aneurysms. There was no difference in outcome events between conservative treatment and endovascular coiling groups. New perioperative neurological deficits were more common in participants treated surgically (16/65, 24.6%; 15.8% to 36.3%) versus 7/69 (10.1%; 5.0% to 19.5%); odds ratio (OR) 2.87 (95% confidence interval (CI) 1.02 to 8.93; P = 0.038). Hospitalization for more than five days was more common in surgical participants (30/65, 46.2%; 34.6% to 58.1%) versus 6/69 (8.7%; 4.0% to 17.7%); OR 8.85 (95% CI 3.22 to 28.59; P < 0.001). Clinical follow-up to one year showed 1/48 clipped versus 1/58 coiled participants had died, and 1/48 clipped versus 1/58 coiled participants had become disabled (modified Rankin Scale > 2). All the evidence is of very low quality., Authors' Conclusions: There is currently insufficient good-quality evidence to support either conservative treatment or interventional treatments (microsurgical clipping or endovascular coiling) for individuals with unruptured intracranial aneurysms. Further randomized trials are required to establish if surgery is a better option than conservative management, and if so, which surgical approach is preferred for which patients. Future studies should include consideration of important characteristics such as participant age, gender, aneurysm size, aneurysm location (anterior circulation and posterior circulation), grade of ischemia (major stroke), and duration of hospitalizations., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Bypass surgery using a large saphenous vein graft, or another autologous venous graft, is a well-recognised treatment option for managing peripheral arterial disease of the lower limb, including chronic limb-threatening ischaemia (CLTI) and intermittent claudication, peripheral limb aneurysms, and major limb arterial trauma. Bypass surgery has good results in terms of limb preservation rates and long-term graft patency but is limited by the possibility of vein graft failure due to stenoses of the graft. Detection of stenoses through clinical and ultrasonographic surveillance, followed by treatment, is used to avoid graft occlusion. The conventional approach to treatment of patients with graft stenosis following infrainguinal bypass consists of open surgical repair, which usually is performed under general anaesthesia. Endoluminal treatment with angioplasty is less invasive and uses local anaesthesia. Both methods aim to improve blood flow to the limb., Objectives: To assess the effectiveness of endoluminal interventions versus surgical intervention for people with vein graft stenosis following infrainguinal bypass., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to 25 August 2020., Selection Criteria: We aimed to include all published and unpublished randomised controlled trials (RCTs) that compared endoluminal interventions versus surgical intervention for people with vein graft stenosis following infrainguinal bypass., Data Collection and Analysis: Two review authors independently assessed all identified studies for potential inclusion in the review. We aimed to use standard methodological procedures in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The main outcomes of interest were primary patency, primary assisted patency, and all-cause mortality., Main Results: We identified no RCTs that met the inclusion criteria for this review., Authors' Conclusions: We found no RCTs that compared endoluminal interventions versus surgical intervention for stenosis in vein grafts following infrainguinal bypass. Currently, there is no high-certainty evidence to support the use of one type of intervention over another. High-quality studies are needed to provide evidence on managing vein graft stenosis following infrainguinal bypass., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Endovascular aortic aneurysm repair (EVAR) is used to treat aorto-iliac and isolated iliac aneurysms in selected patients, and prospective studies have shown advantages compared with open surgical repair, mainly in the first years of follow-up. Although this technique produces good results, anatomic issues (such as common iliac artery ectasia or an aneurysm that involves the iliac bifurcation) can make EVAR more complex and challenging and can lead to an inadequate distal seal zone for the stent-graft. Inadequate distal fixation in the common iliac arteries can lead to a type Ib endoleak. To avoid this complication, one of the most commonly used techniques is unilateral or bilateral internal iliac artery occlusion and extension of the iliac limb stent-graft to the external iliac arteries with or without embolisation of the internal iliac artery. However, this occlusion is not without harm and is associated with ischaemic complications in the pelvic territory such as buttock claudication, sexual dysfunction, ischaemic colitis, gluteal necrosis, and spinal cord injury. New endovascular devices and alternative techniques such as iliac branch devices and the sandwich technique have been described to maintain pelvic perfusion and decrease complications, achieving revascularisation of the internal iliac arteries in patients not suitable for an adequate seal zone in the common iliac arteries. These approaches may also preserve the quality of life of treated individuals and may decrease other serious complications including spinal cord ischaemia, ischaemic colitis, and gluteal necrosis, thereby decreasing the morbidity and mortality of EVAR., Objectives: To assess the effects of internal iliac artery revascularisation versus internal iliac artery occlusion during endovascular repair of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation., Search Methods: The Cochrane Vascular Information Specialists searched the Cochrane Vascular Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 August 2019. The review authors searched Latin American Caribbean Health Sciences Literature (LILACS) and the Indice Bibliográfico Español de Ciencias de la Salud (IBECS) on 28 August 2019 and contacted specialists in the field and manufacturers to identify relevant studies., Selection Criteria: We planned to include all randomised controlled trials (RCTs) that compared internal iliac artery revascularisation with internal iliac artery occlusion for patients undergoing endovascular treatment of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation., Data Collection and Analysis: Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions., Main Results: We identified no RCTs that met the inclusion criteria., Authors' Conclusions: We found no RCTs that compared internal iliac artery revascularisation versus internal iliac artery occlusion for endovascular treatment of aorto-iliac aneurysms and isolated iliac aneurysms involving the iliac bifurcation. High-quality studies that evaluate the best strategy for managing endovascular repair of aorto-iliac aneurysms with inadequate distal seal zones in the common iliac artery are needed., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016., Objectives: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020., Selection Criteria: We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease., Data Collection and Analysis: Two review authors, independently assessed the studies, extracted data and performed data analysis., Main Results: No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure)., Authors' Conclusions: Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Access to the femoral vessels is necessary for a wide range of vascular procedures, including treatment of thromboembolic disease, arterial grafts (i.e. bifemoral aortic bypass or infrainguinal bypass), endovascular repair of abdominal aortic aneurysm (EVAR), thoracic endovascular aneurysm repair (TEVAR) and transcatheter aortic valve implantation (TAVI). The surgical technique used to access the femoral artery may be a factor in the occurrence of postoperative complications; this will be the focus of our review. We will compare the transverse surgical technique-a cut made parallel to the groin crease-versus the vertical groin incision surgical technique-classic technique: a surgical cut made across the groin crease-to access the femoral artery, in an attempt to determine which technique has the lower rate of complications, is safer and is more effective., Objectives: To evaluate the efficacy and safety of transverse groin incision compared with vertical groin incision for accessing the femoral artery in endovascular surgical procedures and open surgery., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases, and the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to 17 February 2020. The review authors searched the IBECS database to 26 March 2020 and reference lists of relevant studies/papers., Selection Criteria: We included randomized controlled trials (RCTs) and quasi-randomized trials (qRCTs) that compare transverse and vertical groin incision, during either endovascular or open surgery procedures., Data Collection and Analysis: Two review authors (MVCRC, FCN) independently selected the studies, assessed risk of bias, extracted data, performed data analysis and graded the certainty of evidence according to GRADE., Main Results: We included one RCT and one qRCT in this review. These two studies had a combined total of 237 participants (283 groins). Infection of the surgical wound was the only outcome that was similar in both studies, and that could therefore be submitted to a combined analysis. Meta-analysis of the two studies showed low-certainty evidence that transverse groin incision resulted in a lower risk of surgical wound infection in the 10- to 28-day period following surgery (risk ratio [RR] 0.25, 95% confidence interval [CI] 0.08 to 0.76; 2 studies; 283 groin incisions). There was low heterogeneity between the studies. We downgraded the certainty of the evidence for surgical wound infection by one level due to serious limitations in the design (there was a high risk of bias in critical domains). The confidence interval for surgical wound infection is relatively wide, further indicating that the certainty of the effect estimate is low. This is likely due to the small number of studies and participants. We observed no evidence of a difference between the two surgical techniques for the other evaluated primary outcome 'lymphatic complications': lymphocele (RR 0.46, 95% CI 0.20 to 1.02; 1 study; 116 groins); and lymphorrhea (RR 2.77, 95% CI 0.92 to 8.34; 1 study; 116 groins). We downgraded the certainty of evidence for lymphatic complications by one level due to serious limitations in the design (there was a high risk of bias in critical domains); and by two further levels because of imprecision (small number of participants and only one study included). High-quality studies are needed to enable a comparison of the two surgical techniques with respect to other outcomes, such as infection of the vascular graft (endoprosthesis/prosthesis), prolonged hospitalization, reoperative surgery, death, neurological deficit (e.g. paresthesia), amputation, graft patency, and postoperative pain., Authors' Conclusions: In this systematic review, we found low-certainty evidence that performing transverse groin incision to access the femoral artery resulted in fewer surgical wound infections compared with performing vertical groin incision. We observed no evidence of a difference between the two surgical techniques for the other evaluated outcomes (lymphocele and lymphorrhea). Other outcomes were not evaluated in these studies. Limitations of this systematic review are, however, the 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., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mmHg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 mmHg to 100 mmHg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. This is an update of a review first published in 2016., Objectives: To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA., Search Methods: The Cochrane Vascular Information Specialist searched the Specialised Register (August 2017), the Cochrane Register of Studies (CENTRAL (2017, Issue 7)) and EMBASE (August 2017). The Cochrane Vascular Information Specialist also searched clinical trials databases (August 2017) for details of ongoing or unpublished studies., Selection Criteria: We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms., Data Collection and Analysis: Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions., Main Results: We identified no RCTs that met the inclusion criteria., Authors' Conclusions: We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Background: The timing of surgery for recently symptomatic carotid artery stenosis remains controversial. Early cerebral revascularization may prevent a disabling or fatal ischemic recurrence, but it may also increase the risk of hemorrhagic transformation, or of dislodging a thrombus. This review examined the randomized controlled evidence that addressed whether the increased risk of recurrent events outweighed the increased benefit of an earlier intervention., Objectives: To assess the risks and benefits of performing very early cerebral revascularization (within two days) compared with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis., Search Methods: We searched the Cochrane Stroke Group Trials Register in January 2016, the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (1948 to 26 January 2016), EMBASE (1974 to 26 January 2016), LILACS (1982 to 26 January 2016), and trial registers (from inception to 26 January 2016). We also handsearched conference proceedings and journals, and searched reference lists. There were no language restrictions. We contacted colleagues and pharmaceutical companies to identify further studies and unpublished trials., Selection Criteria: All completed, truly randomized trials (RCT) that compared very early cerebral revascularization (within two days) with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis., Data Collection and Analysis: We independently selected trials for inclusion according to the above criteria, assessed risk of bias for each trial, and performed data extraction. We utilized an intention-to-treat analysis strategy., Main Results: We identified one RCT that involved 40 participants, and addressed the timing of surgery for people with recently symptomatic carotid artery stenosis. It compared very early surgery with surgery performed after 14 days of the last symptomatic event. The overall quality of the evidence was very low, due to the small number of participants from only one trial, and missing outcome data. We found no statistically significant difference between the effects of very early or delayed surgery in reducing the combined risk of stroke and death within 30 days of surgery (risk ratio (RR) 3.32; confidence interval (CI) 0.38 to 29.23; very low-quality evidence), or the combined risk of perioperative death and stroke (RR 0.47; CI 0.14 to 1.58; very low-quality evidence). To date, no results are available to confirm the optimal timing for surgery., Authors' Conclusions: There is currently no high-quality evidence available to support either very early or delayed cerebral revascularization after a recent ischemic stroke. Hence, further randomized trials to identify which patients should undergo very urgent revascularization are needed. Future studies should stratify participants by age group, sex, grade of ischemia, and degree of stenosis. Currently, there is one ongoing RCT that is examining the timing of cerebral revascularization.

Background: An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mm Hg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 to 100 mm Hg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function., Objectives: To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA., Search Methods: The Cochrane Vascular Information Specialist searched the Specialised Register (April 2016) and the Cochrane Register of Studies (CENTRAL (2016, Issue 3)). Clinical trials databases were searched (April 2016) for details of ongoing or unpublished studies., Selection Criteria: We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms., Data Collection and Analysis: Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions., Main Results: We identified no RCTs that met the inclusion criteria., Authors' Conclusions: We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Background: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain., Objectives: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease., Search Methods: The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies., Selection Criteria: Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease., Data Collection and Analysis: Two review authors, independently assessed the studies, extracted data and performed data analysis., Main Results: Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure., Authors' Conclusions: Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

Background: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain., Objectives: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease., Search Methods: The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies., Selection Criteria: Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease., Data Collection and Analysis: Two review authors, independently assessed the studies, extracted data and performed data analysis., Main Results: Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure., Authors' Conclusions: Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.