vitamin-k-semiquinone-radical and Graft-Occlusion--Vascular

Despite being the most common antithrombotic strategy in trials comparing venous with prosthetic grafts, the use of vitamin K antagonists (VKAs) to improve the outcome of venous bypass remains the subject of debate. In this systematic review, evidence supporting the use of VKAs for improving venous patency following infrainguinal venous bypass is provided.. A 67 year old man with lifestyle limiting claudication underwent a successful infrainguinal venous bypass. Can VKAs help preserve patency after venous bypass surgery?. A systematic review of electronic databases, including MEDLINE and Embase, was conducted. Only randomized controlled studies comparing VKAs with aspirin (ASA) were included. The main outcome was bypass patency.. Four studies using different intensities of anticoagulation ± ASA were identified. All but one showed a benefit of VKAs over ASA with respect to primary patency. However, this benefit was also accompanied by an increased risk of bleeding. The Dutch Bypass Oral Anticoagulants, or ASA, study was the largest included and showed that VKAs (without concomitant ASA) were superior to ASA alone for the prevention of graft occlusion (hazard ratio 0.69, 95% confidence interval 0.54-0.88).. Current evidence suggests that VKAs are superior to ASA for the prevention of infrainguinal autologous venous graft thrombosis.

Topics: Anticoagulants; Graft Occlusion, Vascular; Humans; Inguinal Canal; Vascular Grafting; Vascular Patency; Vitamin K

We investigated the role of oral vitamin K antagonists (VKAs) in graft patency, limb salvage, major and minor bleeding rates in patients undergoing infrainguinal bypass surgery. Five randomized-controlled trials (RCTs; n = 3746 patients) comparing VKA versus non-VKA treatment outcomes in patients undergoing infrainguinal bypass surgery were analyzed. The VKA treatment was associated with improved graft patency rates when a vein graft was used (risk ratio [RR]: 0.74; P = .0004), while there was no difference with prosthetic grafts (RR: 1.07; P = .39). The VKA treatment was also associated with improved limb salvage rates (RR: 0.33; P = .0008). Major and minor bleeding complications were higher in the VKA group. In conclusion, VKA treatment is associated with improved graft patency and limb salvage rates when a vein graft is used at the price of an increased risk of bleeding. Due to the inconsistent results, further well-designed RCTs are needed.

Topics: Administration, Oral; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vascular Grafting; Vascular Patency; Vitamin K

Many cardiac patients require combined antithrombotic therapy consisting of an anticoagulant and inhibition of platelet function. The most frequent indications are atrial fibrillation (AF) in combination with drug-eluting stent implantation and/or the presence of an acute coronary syndrome (ACS). Currently, the optimal combination of anticoagulants and anti-platelet therapy is unknown, but it is well established that the combination of regular doses and regimens as prescribed in AF or after ACS results in increased bleeding rates. In this review, we discuss the current literature and describe approaches to reduce the risk of bleeding hoping not to increase the rate of ischaemic events.

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Embolism; Fibrinolytic Agents; Graft Occlusion, Vascular; Hemorrhage; Humans; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Precision Medicine; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Peripheral arterial disease (PAD) is frequently treated by either an infrainguinal autologous (using the patient's own veins) or synthetic graft bypass. The rate of occlusion of the graft after one year is between 12% and 60%. To prevent occlusion, patients are treated with an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion. This is an update of a Cochrane review first published in 2003.. To evaluate whether antithrombotic treatment improves graft patency, limb salvage and survival in patients with chronic PAD undergoing infrainguinal bypass surgery.. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3).. Randomised, controlled trials; two review authors independently assessed the methodological quality of each trial using a standardised checklist.. Data collected included patient details, inclusion and exclusion criteria, type of graft, antithrombotic therapy, outcomes, and side effects.. A total of 14 trials were included in this review; 4970 patient results were analysed. Four trials evaluating vitamin K antagonists (VKA) versus no VKA suggested that oral anticoagulation may favour autologous venous, but not artificial, graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin (ASA) or aspirin and dipyridamole provided evidence to support a positive effect of VKA on the patency of venous but not artificial grafts. Three trials comparing low molecular weight heparin (LMWH) to unfractionated heparin (UFH) failed to demonstrate a significant difference on patency. One trial comparing LMWH with placebo found no significant improvement in graft patency over the first postoperative year in a population receiving aspirin. One trial showed an advantage for LMWH versus aspirin and dipyridamol at one year for patients undergoing limb salvage procedures. Perioperative administration of ancrod showed no greater benefit when compared to unfractionated heparin. Dextran 70 showed similar graft patency rates to LMWH but a significantly higher proportion of patients developed heart failure with dextran.. Patients undergoing infrainguinal venous graft are more likely to benefit from treatment with VKA than platelet inhibitors. Patients receiving an artificial graft benefit from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers are needed in the future to compare antithrombotic therapies with either placebo or antiplatelet therapies.

Topics: Arteriosclerosis; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Intermittent Claudication; Ischemia; Leg; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

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.. 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.. 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'.. 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.. 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.. 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.. 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 future.

Topics: Arteriosclerosis; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Intermittent Claudication; Ischemia; Leg; Peripheral Vascular Diseases; Postoperative Complications; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

Topics: Anticoagulants; Aspirin; Coronary Artery Bypass; Dipyridamole; Graft Occlusion, Vascular; Humans; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Sulfinpyrazone; Ticlopidine; Vitamin K

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

Topics: Anticoagulants; Aspirin; Coronary Artery Bypass; Dipyridamole; Graft Occlusion, Vascular; Humans; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Sulfinpyrazone; Ticlopidine; Vitamin K

The EPPAC (Etude de la perméabilité des pontages aortocoronaires) is a randomised prospective (18 centres) double blind trial designed to compare the patency of coronary bypass grafts in two groups of coronary patients after surgery: one group treated with oral vitamin-K antagonists and placebo (n = 196, age 57 +/- 5 years, 2.09 grafts/patient) and the other group with vitamin-K antagonists and dipyridamole (n = 182, age 56 +/- 6 years, 1.99 grafts/patient), the principal criterion of evaluation being the patency of the grafts at coronary angiography performed 6 months after surgery, interpreted by two independent observers. Of the 469 patients included (average ejection fraction 59.5 +/- 2.2%), 378 underwent the control coronary angiography at the 6th month and 773 saphenous vein grafts were evaluated. At the end of the study, there were 12 deaths, 10 due to perioperative myocardial infarction, and 24 nonlethal myocardial infarctions. The frequency of occlusion of at least one graft per patient was 18.2%, the patency of the graft at the distal anastomosis was 89.9%. The following factors played a major role: the cardiological center: the occlusion rate per patient ranged from 7.1 to 57.1% and per anastomosis from 2.8 to 28.6%; the internal diameter of the artery grafted: when 2 mm or more, the occlusion rate was 17.6% compared with 42.3% (p less than 0.001); the technique used for distal anastomosis: 9.2% of grafts with single outflow sites occluded, compared with 4.3% of grafts with multiple outflow sites. Early occlusion of saphenous vein aorto-coronary grafts is the main problem of this form of therapy and the addition of dipyridamole to oral anticoagulants does not seem to reinforce the anti-thrombotic effect at 6 months after surgery.

Topics: Adult; Aged; Aspirin; Coronary Angiography; Coronary Artery Bypass; Dipyridamole; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Risk Factors; Vitamin K

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

We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo.. Preclotted and nonpreclotted (collagen-coated) polyester grafts were studied before and 24 hours after implantation into pig femoral arteries. After incubation of explanted grafts was performed with plasma depleted of vitamin K-dependent coagulation factors by barium chloride adsorption (Ba-plasma), graft-associated thrombin activity was determined by radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels reflect thrombin-mediated fibrin formation. Factor Xa activity was characterized by measuring activation of prothrombin added to Ba-plasma.. Thrombin and factor Xa were associated with the luminal surfaces of preclotted grafts before and 24 hours after implantation. Nonpreclotted grafts had negligible procoagulant activity before implantation. After 24 hours in vivo graft-associated factor Xa activity was similar in both nonpreclotted and preclotted grafts; however, more thrombin was bound to nonpreclotted coated grafts (p < 0.01).. The procoagulant activity of small-diameter prosthetic grafts persists for 24 hours after implantation and is attributable not only to graft-associated thrombin but also to de novo thrombin elaboration induced by factor Xa. Moreover, graft-associated procoagulant activity is not dependent on preclotting because it develops on nonpreclotted, collagen-coated grafts as well. Treatment strategies to attenuate graft thrombosis may require the inhibition of both thrombin and factor Xa.

Topics: Adsorption; Animals; Barium Compounds; Blood Coagulation; Blood Vessel Prosthesis; Chlorides; Collagen; Factor Xa; Femoral Artery; Fibrin; Fibrinopeptide A; Graft Occlusion, Vascular; Polyesters; Polyethylene Terephthalates; Prosthesis Design; Prothrombin; Surface Properties; Swine; Thrombin; Thrombosis; Vitamin K