Batroxobin Plus Aspirin Reduces Restenosis After Angioplasty for Arterial Occlusive Disease in Diabetic Patients With Lower-Limb Ischemia
ABSTRACT Aspirin is routinely given to reduce vascular events after angioplasty. Batroxobin has been shown to effectively prevent thrombosis after angioplasty via inhibition of the fibrinogen concentration. In this randomized clinical trial, the hypothesis that batroxobin plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients with diabetes undergoing angioplasty for lower-limb ischemia.
Patients with diabetes and symptomatic arterial obstructions (N = 129) were randomized to receive aspirin 100 mg/d plus batroxobin 5 IU every other day for six doses (n = 58) or aspirin alone (n = 71). The primary outcome was restenosis documented by magnetic resonance (MR) angiography or duplex imaging at 12 months. Secondary outcomes included amputation above the ankle, death, and cumulative rate of amputation or death. Kaplan-Meier analysis was used to evaluate limb salvage and survival rates.
After 12 months, restenosis had occurred in 43.1% and 29.7% of patients in the control and batroxobin groups, respectively (P = .0018). MR angiography and duplex imaging revealed an improved restenosis rate for infrapopliteal lesions and for lesions longer than 10 cm (P = .0016). The primary and cumulative secondary outcomes indicated significant improvements in restenosis rate, symptom relief, and amputation rates in the batroxobin group compared with the aspirin-only group. Kaplan-Meier analysis showed limb salvage and survival rates of 78.3% in the aspirin-only group and 92.2% in the batroxobin group 12 months after angioplasty (log-rank test, P = .0414).
Batroxobin plus aspirin reduced the rate of restenosis after arterial angioplasty, particularly in lesions located below the knee and in those longer than 10 cm, with better clinical symptom relief and improved rate of limb salvage.
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ABSTRACT: Peripheral arterial disease (PAD) is frequently treated by balloon angioplasty. Restenosis/reocclusion of the dilated segments occurs often, depending on length of occlusion, lower leg outflow, stage of disease and presence of cardiovascular risk factors. To prevent reocclusion, patients are treated with antithrombotic agents. This is an update of a review first published in 2005. To determine whether any antithrombotic drug is more effective in preventing restenosis or reocclusion after peripheral endovascular treatment, compared to another antithrombotic drug, no treatment, placebo or other vasoactive drugs. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 February 2012) and CENTRAL (2012, Issue 1). We selected randomised controlled trials (RCTs). Participants were patients with symptomatic PAD treated by endovascular revascularisation of the pelvic or femoropopliteal arteries. Interventions were anticoagulant, antiplatelet or other vasoactive drug therapy compared with no treatment, placebo or any other vasoactive drug. Clinical endpoints were reocclusion, restenosis, amputation, death, myocardial infarction, stroke, major bleeding and other side effects, such as minor bleeding, puncture site bleeding, gastrointestinal side effects and haematoma. We independently extracted and assessed details of the number of randomised patients, treatment, study design, patient characteristics and risk of bias. Analysis was based on intention-to-treat data. To examine the effects of outcomes such as reocclusion, restenosis, amputation and major bleeding, we computed odds ratios (OR) with 95% confidence intervals (CI) using a fixed-effect model. Twenty-two trials with a total of 3529 patients are included (14 in the original review and a further eight in this update). For the majority of comparisons, only one trial was available so results were rarely combined in meta-analyses. Individual trials were generally small and risk of bias was often unclear due to limitations in reporting. Three trials reported on drug versus placebo/control; results were consistently available for a maximum follow-up of only six months. At six months post intervention, a statistically significant reduction in reocclusion was found for high-dose acetylsalicylic acid (ASA) combined with dipyridamole (DIP) (OR 0.40, 95% CI 0.19 to 0.84), but not for low-dose ASA combined with DIP (OR 0.69, 95% CI 0.44 to 1.10; P = 0.12) nor in major amputations for lipo-ecraprost (OR 0.89, 95% CI 0.44 to 1.80). The remaining trials compared different drugs; results were more consistently available for a longer period of 12 months. At 12 months post intervention, no statistically significant difference in reocclusion/restenosis was detected for any of the following comparisons: high-dose ASA versus low-dose ASA (OR 0.98, 95% CI 0.64 to 1.48; P = 0.91), ASA/DIP versus vitamin K antagonists (VKA) (OR 0.65, 95% CI 0.40 to 1.06; P = 0.08), clopidogrel and aspirin versus low molecular weight heparin (LMWH) plus warfarin (OR 0.31, 95% CI 0.06 to 1.68; P = 0.18), suloctidil versus VKA: reocclusion (OR 0.59, 95% CI 0.20 to 1.76; P = 0.34), restenosis (OR 1.87, 95% CI 0.66 to 5.31; P = 0.24) and ticlopidine versus VKA (OR 0.71, 95% CI 0.37 to 1.36; P = 0.30). Treatment with cilostazol resulted in statistically significantly fewer reocclusions than ticlopidine (OR 0.32, 95% CI 0.13 to 0.76; P = 0.01). Compared with aspirin alone, LMWH plus aspirin significantly decreased occlusion/restenosis (by up to 85%) in patients with critical limb ischaemia (OR 0.15, 95% CI 0.06 to 0.42; P = 0.0003) but not in patients with intermittent claudication (OR 1.73, 95% CI 0.97 to 3.08; P = 0.06) and batroxobin plus aspirin reduced restenosis in diabetic patients (OR 0.28, 95% CI 0.13 to 0.60). Data on bleeding and other potential gastrointestinal side effects were not consistently reported, although there was some evidence that high-dose ASA increased gastrointestinal side effects compared with low-dose ASA, that clopidogrel and aspirin resulted in fewer major bleeding episodes compared with LMWH plus warfarin, and that abciximab resulted in more severe bleeding episodes. There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reduced by use of antiplatelet drugs compared with placebo/control, but associated information on bleeding and gastrointestinal side effects is lacking. There is also some evidence of variation in effect according to different drugs with cilostazol reducing reocclusion/restenosis at 12 months compared with ticlopidine and both LMWH and batroxobin combined with aspirin appearing beneficial compared with aspirin alone. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale RCTs, stratified by severity of disease, are required.Cochrane database of systematic reviews (Online) 01/2012; 8(8):CD002071. DOI:10.1002/14651858.CD002071.pub3 · 5.94 Impact Factor
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ABSTRACT: The use of endovascular treatment of infrapopliteal disease has increased in popularity in recent years. An improvement in technical success rates due to the availability of newer devices has fuelled an increased interest in the subject. The pathogenesis, indications for treatment, and outcome measures of infrapopliteal disease differ from larger vessel intervention. Diabetes and renal failure are prevalent. Neuropathy and venous disease contribute to the etiology of ulceration. Most interventions are undertaken for critical limb ischemia rather than claudication. Therefore, a range of conservative, pharmacological, and invasive therapies are provided. Conventional percutaneous transluminal angioplasty (PTA) using modern low-profile systems is associated with high technical success rates. However, initial data from recent randomized, controlled trials suggest that drug-eluting stents are consistently achieving improved patency over PTA alone or over bare metal stents. This review summarizes recent advances in the treatment of infrapopliteal disease.CardioVascular and Interventional Radiology 05/2012; 35(4):715-24. DOI:10.1007/s00270-012-0412-2 · 1.97 Impact Factor