Influence of coumarin treatment on patency and limb salvage after peripheral arterial reconstructive surgery. Can low molecular weight heparin replace unfractionated heparin during peripheral arterial reconstruction? An open label prospective randomized controlled trial. Warfarin improves the outcome of infrainguinal vein bypass grafting at high risk for failure. Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial. Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting. Ancrod versus heparin for anticoagulation during vascular surgical procedures. Low molecular mass heparin instead of unfractionated heparin during infrainguinal bypass surgery. A decade of oral anticoagulant treatment to maintain autologous vein grafts for femoropopliteal atherosclerosis. Benefits, morbidity, and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures: a prospective randomized study. Low molecular weight heparin (enoxaparin) versus dextran in the prevention of early occlusion following arterial bypass surgery distal to the groin. Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery.
The effect of coumarin on patency, limb salvage, and survival after primary femoro-popliteal and femoro-distal reconstructions was studied in 116 randomized patients (61 in the study group and 55 in the control group). All patients were treated postoperatively with heparin. Patients allocated to the study group received dicumarol (a coumarin derivative) orally postoperatively. The overall patency after 1 year was 75 +/- 6%, compared with 74 +/- 6%, after 2 years 65 +/- 9 compared with 57 +/- 8%, and after 3 years 46 +/- 11% compared with 42 +/- 9% (mean +/- SE) in the study and control groups, respectively. There were no statistically significant differences in limb salvage or survival rates between the two groups. In contrast, coumarin treatment was associated with serious bleeding complications in 4% to 5% of the study patients. As expected, limb salvage was lower in patients with critical ischemia (p less than 0.03), and this was also true for survival (p less than 0.04), which was also influenced by the level of the reconstruction; survival was lower in patients with femoro-distal reconstructions (p less than 0.001). Our results demonstrate that coumarin treatment does not improve outcome in routine femoro-popliteal and femoro-distal reconstructive surgery. This study was undertaken to evaluate the effect of low molecular weight heparin (LMWH) compared with unfractionated heparin (UFH) on the rate of occlusion and bleeding during peripheral vascular surgery.
                The study was an open label, prospective, randomized trial, carried out by 20 Swedish surgical and vascular surgical departments that report to the Swedish Vascular Registry (SWEDVASC). Study subjects included patients undergoing peripheral vascular procedures, except carotid surgery. Of the 849 patients included, 817 were followed up to 30 days. LMWH (40 mg of enoxaparin) or UFH (5000 IU heparin) was given intravenously immediately before clamping. The same formulation in diluted form was used for vascular rinsing. Main outcome measures included patent reconstruction at day 1, perioperative blood loss, and the percentage of patients requiring protamin. Further, 30-day data for mortality, repeat operation, and recurrent occlusion are reported.
                The mortality rate at 30 days was 2.7%, with no difference between groups. The patency rate at 1 day was 91.2% to 98.4%, depending on diagnosis and type of reconstruction. No difference was recorded between study groups (0.6 < P < 1.0). At 30 days the patency rate was 83.1% to 100% (0.2 < P <.9). Median blood loss was 350 mL (interquartile range [IQR], 200-800 mL) in the LMWH group and 425 mL (IQR, 200-900 mL) in the UFH group (P =.02). Protamin was given to significantly fewer patients in the LMWH group (P =.001). LMWH was comparable to UFH during peripheral vascular reconstruction in terms of 1-day and 30-day graft patency, operative blood loss, and hemorrhagic complications. Protamine was required less often after LMWH. In this randomized trial LMWH was as effective as UFH in preventing thrombosis without excess bleeding or hemorrhagic complications. Patients with marginal venous conduit, poor arterial runoff, and prior failed bypass grafts are at high risk for infrainguinal graft occlusion and limb loss. We sought to evaluate the effects of anticoagulation therapy after autogenous vein infrainguinal revascularization on duration of patency, limb salvage rates, and complication rates in this subset of patients.
                This randomized prospective trial was performed in a university tertiary care hospital and in a Veterans Affairs Hospital. Fifty-six patients who were at high risk for graft failure were randomized to receive aspirin (24 patients, 27 bypass grafts) or aspirin and warfarin (WAR; 32 patients, 37 bypass grafts). All patients received 325 mg of aspirin each day, and the patients who were randomized to warfarin underwent anticoagulation therapy with heparin immediately after surgery and then were started on warfarin therapy to maintain an international normalized ratio between 2 and 3. Perioperative blood transfusions and complications were compared with the Student t test or with the chi2 test. Graft patency rates, limb salvage rates, and survival rates were compared with the Kaplan-Meier method and the log-rank test.
                Sixty-one of the 64 bypass grafts were performed for rest pain or tissue loss, and 3 were performed for short-distance claudication. There were no differences between the groups in ages, indications, bypass graft types, risk classifications (ie, conduit, runoff, or graft failure), or comorbid conditions (except diabetes mellitus). The cumulative 5-year survival rate was similar between the groups. The incidence rate of postoperative hematoma (32% vs 3.7%; P = .004) was greater in the WAR group, but no differences were seen between the WAR group and the aspirin group in the number of packed red blood cells transfused, in the incidence rate of overall nonhemorrhagic wound complications, or in the overall complication rate (62% vs 52%). The immediate postoperative primary graft patency rates (97.3% vs 85.2%) and limb salvage rates (100% vs 88.9%) were higher in the WAR group as compared with the aspirin group. Furthermore, the cumulative 3-year primary, primary assisted, and secondary patency rates were significantly greater in the WAR group versus the aspirin group (74% vs 51%, P = .04; 77% vs 56%, P = .05; 81% vs 56%, P = .02) and cumulative limb salvage rates were higher in the WAR group (81% vs 31%, P = .01).
                Perioperative anticoagulation therapy with heparin increases the incidence rate of wound hematomas, but long-term anticoagulation therapy with warfarin improves the patency rate of autogenous vein infrainguinal bypass grafts and the limb salvage rate for patients at high risk for graft failure. To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment.
                Prospective randomised double blind multicenter study.
                Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months.
                At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups.
                In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia. Low-molecular weight heparin has theoretical advantages over aspirin and dipyridamole in maintaining vascular-graft patency by virtue of its better antithrombotic effect and antiproliferative activity on vascular, smooth-muscle cells. We tested the hypothesis that low-molecular weight heparin would be more effective than aspirin and dipyridamole in maintaining graft patency in patients undergoing femoropopliteal bypass grafting. Patients were randomised to receive either a daily injection of 2500 IU low-molecular weight heparin, or 300 mg aspirin with 100 mg dipyridamole 8 hourly for 3 months. 94 patients were randomised to low-molecular weight heparin and 106 to aspirin and dipyridamole. Patients were stratified according to indication for surgery and were followed up for 1 year. Kaplan-Meier estimate of graft patency showed 87% graft survival on low-molecular-weight heparin and 72% on aspirin and dipyridamole at 6 months. At 12 months, the respective figures were 78% and 64%. Stratified survival analysis showed that this benefit was confined to those having salvage surgery (log rank test p = 0.0006); for those having surgery for claudication there was no significant benefit. No major bleeding events occurred in either group. We conclude that low-molecular weight heparin is better than aspirin and dipyridamole in maintaining femoropopliteal-graft patency in patients with critical limb ischaemia undergoing salvage surgery. This treatment should have considerable cost benefits. The purpose of this study was to compare the conduct and early results of infrainguinal vascular reconstructions with use of ancrod or heparin for anticoagulation.
                To test the hypothesis that ancrod was an effective alternative to heparin, 28 patients requiring infrainguinal bypass surgery were randomized to receive heparin during operation or ancrod before operation over a period of 12 hours to deplete circulating fibrinogen (0.2 to 0.5 gm/L).
                No clotting of blood within the grafts or native vessels was noted during the conduct of the surgical procedures in either group. No excessive bleeding was detected during operation in either group. The operative procedure, complication rate, and hospital course were also indistinguishable; patency at 1 month was also equal.
                Fibrinogen depletion with ancrod provides anticoagulation for the conduct of infrainguinal vascular reconstructions that is as effective as heparin. When heparin is contraindicated ancrod is an effective and safe alternative. To test whether low molecular mass heparin (LMMH) is comparable to unfractionated heparin (UFH) as an anticoagulant during infrainguinal bypass surgery and to investigate laboratory evidence of hypercoagulation in patients undergoing infrainguinal bypass surgery.
                Eighteen patients were randomised to receive either UFH or LMMH (70 anti-Xa units/kg b.w.). Soluble fibrin, measured as fibrin monomers (FM) and fibrinopeptide A (FPA), were measured in blood from the femoral vein before, during and after release of the occluding clamps during surgery. In addition, fibrinogen prothrombin complex, thrombin-antithrombin complex, platelets and antithrombin were measured before surgery. Heparin levels (Anti Xa) were measured during surgery.
                Increased levels of fibrinogen, FPA, thrombin antithrombin complex and FM were recorded prior to surgery. During surgery no further increase was noted. The anti Xa levels were slightly higher in patients with LMMH than in patients receiving UFH. Levels of FM were significantly lower in patients receiving LMMH. No difference in FPA was noted. A positive correlation between fibrinogen and FPA and FM respectively was recorded. Four patients, two in each group, were reoperated for graft occlusion. One patient in the UFH group required reoperation because of bleeding.
                LMMH is comparable to UFH as an anticoagulant during infrainguinal bypass surgery. Variables reflecting hypercoagulability are elevated in this group of patients and are positively correlated to the fibrinogen level. High fibrinogen levels could thus be a risk for perioperative thrombosis. To determine whether long-term oral anticoagulant treatment was effective in improving graft performance and preventing major amputation following vein bypass surgery for femoropopliteal atherosclerosis, a clinical trial was conducted in one single center and continued during 10 years. After 130 patients had electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group (treatment with phenprocoumon [n = 66]) or to a control group (n = 64) that remained without any anticoagulant treatment. Primary end points of the study were graft reocclusion and limb loss. The median durations of primary patency and limb salvage were significantly longer for treated patients than that for controls. In addition, survival in the therapy group was longer. Following autologous vein bypass surgery in the treated group, the results were superior in terms of graft patency, limb salvage, and survival. The benefits of the long-term administration of oral anticoagulant therapy remain unclear in patients with lower extremity arterial bypass surgery. We studied the effect of warfarin plus aspirin therapy (WASA) versus aspirin therapy alone (ASA) on patient mortality, morbidity and bypass patency rates in a randomized clinical trial.
                In a multicenter, prospective, nonmasked clinical trial, 831 patients who underwent peripheral arterial bypass surgery were compared in a long-term treatment program of WASA (target international normalized ratio of 1.4 to 2.8; 325 mg/day) with ASA (325 mg/day). The primary end point was bypass patency, and mortality and morbidity were the secondary endpoints.
                There were 133 deaths in the WASA group (31.8%) and 95 deaths in the ASA group (23.0%; risk ratio, 1.41; 95% confidence interval, 1.09 to 1.84; P =.0001). Major hemorrhagic events occurred more frequently in the WASA group (WASA, n = 35; ASA, n = 15; P =.02). In the prosthetic bypass group, there was no significant difference in patency rate in the 8-mm bypass subgroup, but there was a significant difference in patency rate in the 6-mm bypass subgroup (femoral-popliteal; 71.4% in the WASA group versus 57.9% in the ASA group; P =.02). In the vein bypass group, patency rate was unaffected (75.3% in the WASA group versus 74.9% in the ASA group).
                The long-term administration of warfarin therapy when combined with aspirin therapy has only a few selected indications for improvement of bypass patency and is associated with an increased risk of morbidity and mortality. to compare the effect of perioperative dextran and low molecular weight heparin on early graft patency after femorodistal bypass surgery.
                prospective randomised multicentre study.
                three hundred and fourteen patients were randomised to dextran 70 or the low molecular weight heparin enoxaparin during and after femorodistal bypass surgery. Patency was evaluated at days 1, 5-7, 30 and 90.
                there was no difference in patency at any time point between the two regimens, the crude 90 days patency being 88 and 83%, respectively. There were significantly more patients with heart failure in the dextran group (12.8 vs 0.7%), with other side effects being evenly distributed.
                dextran 70 and the low molecular weight heparin enoxaparin have the same effect on 90 days femorodistal graft patency, but care must be taken using the dextran to patients with a potential heart insufficiency. Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.