Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial. Effects of aspirin and dipyridamole on expanded polytetrafluoroethylene graft patency. [Experiences with adjuvant prostaglandin therapy in vascular surgery interventions]. Indobufen vs acetylsalicylic acid plus dipyridamole in long-term patency after femoropopliteal bypass. Effect of aspirin and dipyridamole on the patency of lower extremity bypass grafts. Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting. Random control trial of a short course of aspirin and dipyridamole (Persantin) for femorodistal grafts. Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs. Etude de la Ticlopidine après Pontage Fémoro-Poplité and the Association Universitaire de Recherche en Chirurgie. Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial. Prevention of post-operative thrombosis in peripheral arteriopathies. Pentoxifylline vs. conventional antiaggregants: a six-month randomized follow-up study.
Oral anticoagulants and aspirin are antithrombotic drugs that are commonly used in patients with vascular disease. We investigated whether either of these treatments prevented more effectively than the other bypass complications after infrainguinal bypass surgery.
                We did a multicentre, randomised, open trial. 2690 patients who had undergone infrainguinal grafting were randomly assigned oral anticoagulants (target international normalised ratio 3.0-4.5, n=1339) or aspirin (80 mg daily, n=1351). We followed up patients for a mean of 21 months. The primary outcome was graft occlusion.
                308 graft occlusions occurred in the oral-anticoagulants group compared with 322 in the aspirin group (hazard ratio 0.95 [95% CI 0.82-1.11]), which suggested no overall advantage for either treatment. Oral anticoagulants were beneficial in patients with vein grafts (0.69 [0.54-0.88]), whereas aspirin had better results for nonvenous grafts (1.26 [1.03-1.55]). The composite outcome of vascular death, myocardial infarction, stroke, or amputation occurred 248 times in the oral-anticoagulants group and 275 times in the aspirin group (0.89 [0.75-1.06]). Patients treated with oral anticoagulants had more major bleeding episodes than those treated with aspirin (108 vs 56; 1.96 [1.42-2.71]).
                Oral anticoagulation was better for the prevention of infrainguinal-vein-graft occlusion and for lowering the rate of ischaemic events. Aspirin was better for the prevention of non-venous graft occlusion, and was associated with fewer bleeding episodes. A randomized, double-blind clinical trial was designed to assess the effect of aspirin (ASA) alone or in combination with dipyridamole (DIP) on the patency rates of expanded PTFE grafts placed in the infrainguinal position. Forty-nine patients were randomized into three groups who received three times daily either two placebos (17 patients), 325 mg ASA and placebo (16 patients), or 325 mg ASA and 75 mg DIP (16 patients). The patients were seen at 3-month intervals for 1 year, and coded medication bottles were dispensed and returned pills counted to assess patient compliance. Treatment failure was defined as the first graft occlusion. The data were analyzed using the Breslow statistic for progressively censored survival type data. The 1-year cumulative patency rate for the entire series was 59%. The rates for above-knee grafts in the ASA group (100%) and the ASA/DIP group (100%) were significantly higher than the rates for the placebo group (50%) (P = 0.05). The 1-year cumulative patency rates for patients with below-knee grafts were not statistically different among the groups, although the patients who received ASA alone had a higher rate than did the other two groups (65% versus 21% for placebo and 19% for ASA/DIP). There were fewer occlusions in the above-knee grafts as compared to below-knee grafts in all groups, but the differences were statistically significant only in the ASA/DIP group. There were no statistical differences between the two active treatment groups. Two prospective randomized trials were referred. In the first study 50 patients with femorotibial greater saphenous vein in situ bypasses were treated intraarterially with 0.2 ng PGE 1/kg body weight/min and 15,000 i.U. of heparine continuously. The control group of 50 patients also got 15,000 i.U. of heparine and 3 x 0.5 g of Aspirin. We observed 2 (4%) immediate occlusions in the PGE 1 group and 7 (14%) immediate occlusions in the control group. This difference proved to be statistically significant. In the second study 83 patients with three level occlusions (ilio-femoro-tibial) in stage III and IV were treated with a profundaplasty. 42 patients received 60 micrograms PGE 1 in 250 ml saline twice daily. The control group of 41 patients only got twice 250 ml saline over a period of three weeks. In the PGE 1 group 26 patients (61%) showed disappearance of rest pain and healing of necrotic lesions, whereas in the control group this could only be achieved in 15 patients (35%). The difference proved to be statistically significant. To compare the effects of indobufen (INB) with those of ASA+dipyridamole (DP) on graft patency, 113 patients undergoing femoropopliteal bypass surgery were randomly and blindly assigned to treatment with INB 400 mg daily or with ASA 900 mg daily plus DP 225 mg daily. Treatment started 2 days before surgery and lasted for 12 months. All patients underwent two angiographic examinations: the first early after surgery (mean 6 days) and the second at the end of the study (mean 368 days). The 1 year cumulative patency rate for INB was 60% higher but not statistically different from the ASA-DP group (53.2%). The relative risk (INB/ASA+DP) calculated by the Mantel-Haenszel test was 0.86 (confidence limits 0.54-1.35). Only the site of operation (above-knee or below-knee) has a significant prognostic value on the fate of the graft. Recent clinical studies indicate that the use of aspirin and dipyridamole improves graft patency rates in patients with infrainguinal polytetrafluoroethylene (PTFE) grafts and aortocoronary vein grafts. We undertook a prospective, double-blind, randomized study to determine whether these drugs administered postoperatively to patients with PTFE or autologous vein infrainguinal bypasses would improve graft patency during the first 24 months after operation. Patients received either aspirin 325 mg and dipyridamole 75 mg or identical placebo tablets three times a day, taken orally. Patency rates were compared by computing standard life tables and comparing cumulative patency rates. One hundred patients with 102 grafts were studied. The cumulative patency rate at 24 months was not significantly different for the treatment (57%) versus control (67%) groups or for any subgroup. We conclude that aspirin and dipyridamole administered postoperatively in the doses used in this study do not improve the overall patency rates of vein or PTFE infrainguinal bypass grafts. 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 effect of a short course of anti-platelet agents, started preoperatively, on the patency of femorodistal bypass grafts is unknown. One hundred and forty-eight such grafts were randomized to act as controls or to receive dipyridamole 200 mg b.d. for 48 h pre-operatively and dipyridamole 200 mg b.d. with aspirin 300 mg daily for 6 weeks after surgery. Patients were well-matched and the mean pre-operative pressure index of 0.37 rose to 0.78 during the first postoperative week. No deaths were attributable to the treatment. Ninety-three grafts were autogenous vein and the remainder were prosthetic (GORE-TEX (PTFE), human umbilical vein or externally supported Dacron). At 1 year autogenous vein cumulative patency was 75 per cent. Overall results showed higher patency in the treated group (P = 0.012) which was entirely accounted for by the difference between prosthetic dipyridamole and aspirin group (85 per cent patency) and prosthetic control groups (53 per cent patency, P = 0.005) and arose during the first postoperative month. There were 11 deaths and 8 amputations in the dipyridamole and aspirin group and 8 deaths and 12 amputations in the control group. It is concluded that a six week perioperative course of dipyridamole and aspirin allows the patency of prosthetic femorodistal bypass to approach that of autogenous vein, and the regimen therefore is recommended for patients who may require a prosthetic graft. Optimal therapy to prevent late occlusion of arterial bypass grafts in the legs has not been determined. We assessed the effect of ticlopidine, an inhibitor of platelet aggregation, on the long-term patency of saphenous-vein bypass grafts for the treatment of peripheral vascular disease.
                A total of 243 patients with femoropopliteal or femorotibial saphenous-vein bypass grafts were randomly assigned to receive either ticlopidine (250 mg twice a day) or matching placebo for two years. The primary end point was graft patency at two years, as assessed by physical examination, measurement of the ankle brachial index, and duplex ultrasonography or arteriography. The incidence of death and major ischemic events was also analyzed in the two groups.
                After two years, 66.4 percent of the patients were alive with a patent graft in the ticlopidine group, as compared with 51.2 percent in the placebo group (95 percent confidence interval for the difference between the two groups, 2.9 to 27.4 percent; P=0.02). The two-year cumulative patency rate was 82 percent in the ticlopidine group and 63 percent in the placebo group (P=0.002). There was no significant difference between groups in overall mortality or major ischemic events.
                Ticlopidine significantly improved the long-term patency of saphenous-vein bypass grafts in the legs. Since the drug was well tolerated, its use can be recommended after peripheral-vein bypass surgery. To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease. The patency rate and reocclusion incidence were studied in 97 patients following vascular surgery necessitated by occlusion in the aortoiliac or femoropopliteal regions or both. Forty-nine patients were treated orally with a combination of acetylsalicylic acid and dipyridamole (1050 mg + 150 mg/day) and 48 patients with the haemorheologically active agent pentoxifylline (1200 mg/day, Trental 400 tds.) for uniform periods of 6 months. Reocclusion occurred in 10 patients receiving ASAD and in 5 patients receiving pentoxifylline. Adverse reactions were recorded in 12 patients with ASAD (discontinuation in 11) and in 3 patients with pentoxifylline (discontinuation in 2). Patency and tolerability rate were significantly superior in those patients treated with pentoxifylline, suggesting that the combination of haemorheological effects with antihaemostaseological and antithrombotic properties offered by pentoxifylline may be of benefit in the prevention of reocclusion after vascular surgery.
Antiplatelet therapy with aspirin had a slight beneficial effect on the patency of peripheral bypass grafts but seemed to have an inferior effect on venous graft patency compared with artificial grafts. The effect of aspirin on cardiovascular outcomes and survival was small and not statistically significant. This might be due to the fact that the majority of patients receiving a peripheral graft have an advanced stage of PAD with critical ischaemia. They are usually seriously ill as a result of cardiovascular disease and have high mortality rates, of 20% per year. Additionally, the number of patients included in this analysis might be too small to reach a statistically significant effect for mortality and cardiovascular morbidity.