acenocoumarol and Graft-Occlusion--Vascular

Secondary prophylaxis using aspirin is standard of care after coronary artery bypass graft surgery. Limited data are available for long-term results. We evaluated the effect of aspirin, aspirin with dipyridamole, and vitamin K antagonists (VKA) on 14-year clinical outcome of patients included in the Prevention of Coronary Artery Bypass Graft Occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study (CABADAS).. All 726 Dutch patients for whom antithrombotic therapy with aspirin (n = 248), aspirin with dipyridamole (n = 234), or VKA (n = 244) was randomly allocated were included. The primary endpoint was occurrence of major adverse cardiac events (MACE). Outcomes were retrospectively evaluated during 14-year follow-up.. Cumulative incidences for MACE over 14 years were 49%, 50%, and 59% for patients treated with aspirin, aspirin with dipyridamole, and VKA, respectively. Although the overall occurrence of MACE did not significantly differ among the three treatment groups (p = 0.12), patients treated with VKA were at higher risk of MACE than patients treated with aspirin with dipyridamole (hazard ratio 1.3, 95% confidence interval: 1.0 to 1.8, p = 0.041) and patients treated with aspirin alone (hazard ratio 1.1, 95% confidence interval: 0.86 to 1.5, p = 0.37). This difference was attributed to an increased risk of repeat revascularization in patients treated with VKA, without any differences in cardiac death and myocardial infarction among the three treatment groups. However, the observed high rate of repeat revascularization in patients treated with VKA could reflect an a priori increased probability for repeat revascularization due to the specific conditions surrounding VKA therapy (ie, more intense patient-doctor contacts).. This study with 14-year clinical outcome provides further evidence for the use of aspirin as secondary prophylaxis after coronary artery bypass graft surgery.

Topics: Acenocoumarol; Aged; Anticoagulants; Aspirin; Coronary Artery Bypass; Dipyridamole; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Phenprocoumon; Vitamin K

The purpose of this study was to determine the optimal intensity of oral anticoagulation in patients who participated in a randomized trial of oral anticoagulants or aspirin after infrainguinal bypass graft surgery.. The distribution of patient-time spent in international normalized ratio (INR) classes of 0.5 INR unit was calculated assuming a linear change between successive measurements. INR-specific incidence rates of ischemic and hemorrhagic events were calculated as the ratio of the number of events at a certain INR category and the total patient-time spent in that class. The relationship between INR class and event rates was quantified by rate ratios calculated in a Poisson regression model.. In 1326 patients (mean age, 69 years) 41,928 INR measurements were recorded in 1698 patient-years. Patients spent 50% of the total time within the target range of 3.0 to 4.5 INR. Most of the patient-time (60%) was spent between 2.5 and 3.5 INR. For each increasing class of 0.5 INR, the incidence of ischemic events (n = 154, INR data on event available in 49%) decreased by a factor of 0.97 (95% CI, 0.87-1.08). The incidence of major bleeding (n = 123, INR data on event available in 65%) increased significantly by a factor of 1.27 (95% CI, 1.19-1.34) for each increasing 0.5 INR category. The optimal target range was 3.0 to 4.0 INR, with an incidence of 3.8 events (0.9 ischemic and 2.9 hemorrhagic) per 100 patient-years.. The target range of 3.0 to 4.0 INR is the optimal range of achieved anticoagulation intensity and is safe for the prevention of ischemic events in patients after infrainguinal bypass graft surgery.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Aspirin; Blood Vessel Prosthesis Implantation; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; International Normalized Ratio; Ischemia; Leg; Male; Middle Aged; Netherlands; Phenprocoumon; Treatment Outcome

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.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Aspirin; Female; Graft Occlusion, Vascular; Humans; Leg; Male; Phenprocoumon; Platelet Aggregation Inhibitors; Vascular Surgical Procedures

This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anticoagulant agents in the prevention of internal mammary artery graft occlusion.. Antithrombotic drugs increase vein graft patency after coronary artery bypass surgery. Their benefit after internal mammary artery grafting has not been established.. Angiographic internal mammary artery graft patency at 1 year was assessed in 494 patients who received both internal mammary artery and vein grafts. These patients were a subgroup of a prospective, randomized vein graft patency study in 948 patients assigned to treatment with aspirin, aspirin plus dipyridamole, or oral anticoagulant agents. The design was double-blind for both aspirin groups and open for oral anticoagulant treatment. Dipyridamole (5 mg/kg body weight per 24 h intravenously, followed by 200 mg twice daily) and oral anticoagulant agents (prothrombin time target range 2.8 to 4.8 international normalized ratio) were started before operation, and low dose aspirin (50 mg/day) after operation. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding or death.. Occlusion rates of distal anastomoses were 4.6% in the aspirin plus dipyridamole group and 6.8% in the oral anticoagulant group versus 5.3% in the aspirin group (p = NS). Overall clinical event rates were 23.3% and 13.3% in the aspirin plus dipyridamole group and the aspirin group, respectively (relative risk 1.75, 95% confidence interval 1.09 to 2.81, p = 0.025), and 17.1% in the oral anticoagulant group.. Internal mammary artery graft patency at 1 year is not improved by aspirin plus dipyridamole or oral anticoagulant agents over that obtained with low dose aspirin alone. However, there is evidence that the overall clinical event rate increases if dipyridamole is added to aspirin.

Topics: Acenocoumarol; Anticoagulants; Aspirin; Dipyridamole; Double-Blind Method; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Humans; Internal Mammary-Coronary Artery Anastomosis; Male; Middle Aged; Phenprocoumon; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency

From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aspirin; Coronary Artery Bypass; Coronary Circulation; Coronary Disease; Dipyridamole; Drug Therapy, Combination; Exercise Test; Female; Fibrinolytic Agents; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Prospective Studies; Radionuclide Imaging; Saphenous Vein; Thallium Radioisotopes; Treatment Outcome

Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been established. We assessed one-year angiographic vein-graft patency after aortocoronary-bypass surgery in 948 patients assigned to receive aspirin, aspirin plus dipyridamole, or oral anticoagulants in a prospective, randomised trial. The design was double-blind and placebo-controlled for the aspirin groups, but open for oral anticoagulant treatment. Dipyridamole (5 mg/kg per 24 h intravenously for 28 h, followed by 200 mg twice daily) and oral anticoagulants (desired prothrombin time range 2.8-4.8 international normalised ratio) were started before surgery, and aspirin (50 mg per day) was started after surgery. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, or death. Occlusion rate of distal anastomoses was 11% in the aspirin plus dipyridamole group versus 15% in the aspirin group (relative risk 0.76, 95% CI 0.54-1.05) and 13% in the oral anticoagulants group. Clinical events occurred in 20.3% of patients receiving aspirin plus dipyridamole compared with 13.9% of the aspirin group (relative risk 1.46, 95% CI 1.02-2.08) and 16.9% of the oral anticoagulants group. Our data provide no convincing evidence that addition of dipyridamole to 50 mg aspirin per day improves aortocoronary vein-graft patency. Moreover, there is evidence that the combination increases the overall clinical-event rate. Compared with aspirin, oral anticoagulants provided no benefit.

Topics: Acenocoumarol; Administration, Oral; Aged; Aspirin; Coronary Artery Bypass; Dipyridamole; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Phenprocoumon; Treatment Outcome; Vascular Patency

The effects of the antiaggregant substance ticlopidine and of the anticoagulant acenocoumarol on patency rates of aorto-coronary bypass grafts were compared in a prospective randomized trial. Ticlopidine, 250 mg b.i.d. was administered orally from the first postoperative day till angiography, while anticoagulation with acenocoumarol was initiated on the second to third postoperative day. Side-effects of ticlopidine were rare and patient management with the standard dosage of this drug was easier than oral anticoagulation. From an initial group of 166 randomized patients 149 completed the trial by coronary angiography three months postoperatively. The 78 patients in the ticlopidine group showed a compliance of 85%. The average prothrombin time in the 71 patients receiving acenocoumarol was 26.9%. Detailed statistical analysis of the two study groups revealed no reason to doubt the correctness of randomization. Coronary angiography showed an average patency rate per patient of 84% with ticlopidine and of 82% with acenocoumarol. This and various other measures of graft occlusion did not reveal any substantial difference in graft patency of patients receiving ticlopidine or acenocoumarol. It is concluded that ticlopidine may well be used instead of anticoagulants for prevention of postoperative occlusion of aorto-coronary bypass grafts.

Topics: Acenocoumarol; Anticoagulants; Clinical Trials as Topic; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Graft Occlusion, Vascular; Humans; Middle Aged; Postoperative Complications; Thiophenes; Ticlopidine

Topics: Acenocoumarol; Anticoagulants; Aspirin; Coronary Artery Bypass; Dipyridamole; Graft Occlusion, Vascular; Humans; Phenprocoumon; Vitamin K

A male patient had been treated with acenocoumarol for 9 years. Raised white cell count returned to normal, when acenocoumarol was substituted by heparin, but rose again after reexposure. An analysis of variance showed that this effect is mediated by neutrophils only. The rise is quick and may therefore be caused by a redistribution of white cells rather than by increased cell production.

Topics: Acenocoumarol; Adult; Aorta, Thoracic; Aortic Aneurysm; Aortic Dissection; Blood Vessel Prosthesis; Graft Occlusion, Vascular; Granulocytes; Heparin; Humans; Leukocyte Count; Leukocytosis; Male; Postoperative Complications