Antithrombotic agents for preventing thrombosis after infrainguinal arterial bypass surgery

BACKGROUND: Chronic peripheral arterial disease (PAD) is frequently treated by implantation of either an infrainguinal autologous venous or artificial graft. One-year occlusion rates for infrainguinal bypasses vary between 15 and 75%, depending on the site of distal anastomosis, length, quality, and material of the graft, but also on other factors such as proximal inflow and distal outflow conditions. To prevent graft occlusion, patients are usually treated with either an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion. OBJECTIVES: To evaluate whether antithrombotic treatment in patients with chronic PAD undergoing infrainguinal bypass surgery improves graft patency, limb salvage and survival by performing a meta-analysis of performed RCTs. SEARCH STRATEGY: The search strategy was that adopted by the Cochrane Review Group on Peripheral Vascular Diseases. Additional data bases were reviewed (Reference lists of papers resulting from this search, MEDLINE from 1966-onwards and EMBASE from 1980-onwards using the terms 'anticoagulant' and 'arterial surgery'. SELECTION CRITERIA: The methodological quality of each trial was assessed independently by at least two reviewers using the checklist provided by the Peripheral Vascular Diseases Collaborative Review Group, with emphasis on concealment of randomisation. Each trial was given an allocation score of A (clearly concealed), B (unclear if concealed), or C (clearly not concealed) and a summary score of A (low risk of bias), B (moderate risk), or C (high risk). Trials scoring A were included and those scoring C were excluded. For a trial scoring B, an attempt was made to obtain more information by contacting the author. DATA COLLECTION AND ANALYSIS: For each trial, the number of patients originally allocated to each treatment group was extracted from the data and an 'intention to treat' analysis performed. Data collection on each trial included inclusion and exclusion criteria, patient details, type of graft, type and dose of antithrombotic therapy used, outcome, and side effects. The treatment and control groups were compared for important prognostic factors and differences described. If any of the above data was not available, further information was sought from the author. However, the heterogeneity between trials could not be tested due to inaccessible data. Data were synthesized by comparing group results. MAIN RESULTS: The analysis including four trials which evaluated vitamin K antagonists (VKA) versus no VKA indicate, that oral anticoagulation tendentially favours venous but not artificial graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin or aspirin/dipyridamole supported evidence for a positive effect of VKA on the patency of venous but not artificial grafts. Subgroup analysis for artificial grafts as performed in one trial showed a favourable effect of antiplatelet agents on synthetic bypasses. In two trials with a relatively small number of patients low molecular weight heparin treatment was associated with a lower incidence of early postoperative graft thrombosis compared to treatment with unfractionated heparin. In one trial infusion of antithrombin concentrate was reported to have a negative effect on intraoperative graft thrombosis necessitating the study to be stopped before termination. Perioperative administration of ancrod was compared to unfractionated heparin showing no benefit of one drug compared to the other. REVIEWER'S CONCLUSIONS: Patients operated for an infrainguinal venous graft might benefit from treatment with VKA, whereas patients receiving an artificial graft might profit more from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers comparing antithrombotic therapies with either placebo or antiplatelet therapies are called for in the futur

Mouse models of focal arterial and venous thrombosis

Mouse models of arterial and venous thrombosis have gained increasing interest over the last 15 years, due to direct availability of a growing number of genetically modified mice, improved technical feasibility, standardization of new models of local thrombosis, and low maintenance costs. In order to provide an overview of suitable models for the study of arterial and venous thrombosis in mice, we have systematically searched MEDLINE electronic databases for publications reporting on murine thrombo-embolic models from 1966-1999. We found that the variety of murine thromboembolic models through 1995 was rather limited, as most methods used intravenous injections of strong coagulation triggers such as thrombin, thromboplastin and collagen, causing lethal thromboembolism. Between 1996 and the end of 1999, a number of more sophisticated murine models of local acute or chronic thrombosis have been established. They seem to be more suitable for mimicking the natural scenario of thrombosis and, therefore, are preferable models for pathophysiological or drug evaluation studies. In this paper various models are described and their advantages and limitations discusse

Influence of secondary infection on amputation in chronic critical limb ischemia

OBJECTIVES: To evaluate the influence of secondary infection on major amputation in chronic critical leg ischemia (CLI). DESIGN: Prospective, controlled observational study. MATERIALS AND METHODS: Sixty-seven patients with CLI and ischemic lesions participated in the study. Presence of infection was defined by clinical, laboratory and radiological criteria. Patients were categorized as having no local infection, soft tissue infection or osteomyelitis treated without antibiotics, amoxicillin/clavulanacid for 1 month or ciprofloxacin and clindamycin for 3 months, respectively. Clinical outcome was assessed at 2, 6 and 12 months. Study endpoints were major amputation and mortality. Analyses were performed using the Kaplan-Meier method. RESULTS: Forty-seven of 67 patients had a local infection. Major amputation was lower in patients with successful revascularization as compared to patients unsuitable for or with failed (without) revascularization (0% vs 26%, p<0.01). In patients with successful revascularization the probability of complete healing was lower with secondary infection (23% vs 71%, p=0.03). In patients without revascularization complete healing was rare (<10%), but secondary infection did not influenced major amputation, mortality or serious adverse events. CONCLUSION: Secondary infection reduces the likelihood of successful healing following revascularisation of CLI