Oral Anticoagulant Group Research Articles

Aspirin or Anticoagulants in Stenosis of the Middle Cerebral Artery:A Randomized Trial

Background: We report the results of an open, randomized, multicenter trial that compared the efficacy of aspirin to oral anticoagulants (OA) for the prevention of vascular events in patients with symptomatic stenosis of the middle cerebral artery (MCA). Methods: Participants were randomly assigned to receive 300 mg/day of aspirin or a dose of OA (target INR 2–3). The MCA stenosis was demonstrated by conventional angiography or by at least two noninvasive examinations. Patients had either transient ischemic attack or cerebral infarct (CI) attributable to the MCA stenosis within 90 days before inclusion. The primary endpoint was: nonfatal CI, nonfatal acute myocardial infarct, vascular death and major hemorrhage. The patients were followed-up for a minimum of 1 year and a maximum of 3 years. Results: The study included 28 patients (14 in each treatment group); the average age was 67 ± 9.9 years. Men constituted 68% of the patients. After a mean follow-up of 23.1 ± 10.9 months, there were no recurrences of CI in both groups. No endpoint was reported in the aspirin group, but 2 patients in the OA group (14.3%) exhibited vascular events: 1 acute myocardial infarct and 1 intracerebral hemorrhage). However, this difference was not statistically significant (p = 0.48). Conclusions: Our study suggests that aspirin is the treatment of choice for the prevention of vascular events in patients with symptomatic MCA stenosis.

Anticoagulation Therapy in Atrial Fibrillation in Combination With Acute Myocardial Infarction Influences Long-Term Outcome

The American and European guidelines do not agree with regard to antithrombotic treatment in patients with atrial fibrillation (AF) and acute myocardial infarction (AMI), thus causing uncertainty among physicians. We investigated the prescription of oral anticoagulation (OAC) in patients discharged alive with AF after an AMI and the influence of OAC treatment on 1-year mortality. This was a prospective cohort study using data from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA) on patients admitted to the coronary care units of 72 Swedish hospitals from 1995 to 2002. A total of 6182 patients discharged alive with first registry-recorded AMI and AF on discharge ECG were included. One-year mortality data were obtained from the Swedish National Cause of Death Register. Only 30% (n=1848) of the 6182 patients with AF were prescribed OAC. At 1 year, the unadjusted mortality was 31% (1183 deaths) in the platelet-inhibitors only group and 22% (414 deaths) in the OAC-treated group. In Cox regression analysis with adjustment for confounding factors, OAC treatment was associated with a reduction in 1-year mortality (relative risk 0.73; 95% CI 0.62 to 0.86; P<0.001) in hospital survivors of AMI with AF. The reduction in mortality appeared to be caused primarily by a lower rate of ischemic heart death (55.6% versus 62.0%) and fatal stroke (5.7% versus 7.5%) in the OAC group. This reduction of mortality was similar among most subgroups based on age, sex, baseline characteristics, previous disease manifestations, and medications. In daily clinical practice, OAC was only given to a minority (30%) of AMI patients with AF, despite the fact that OAC was associated with a 29% relative and 7% absolute reduction in 1-year mortality after adjustment for confounding variables. The results emphasize the importance of OAC treatment for AF after AMI.

Selecting an anticoagulant for recurrent venous thromboembolism in cancer

Purpose. The thrombogenicity of newer anticancer agents and the challenges associated with managing cancer patients on warfarin have led to the evaluation of the low-molecular-weight heparins (LMWHs) for primary and secondary prophylaxis in this high-risk patient population. Summary. The first published trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were then randomized to continue receiving enoxaparin or begin warfarin therapy. Due to inadequate patient enrollment, no statistically significant differences were detected between the two treatment groups. In a similar patient population, the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial evaluated the use of long-term dalteparin for the prevention of recurrent venous thromboembolism (VTE) in patients with cancer. Cancer patients with proximal DVT, PE, or both were randomized to initial treatment with dalteparin followed by either six months of oral anticoagulant therapy or dalteparin monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary outcomes were bleeding events and survival time. The cumulative risk of recurrent VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in the dalteparin group, a risk reduction of 52% (p=0.002). No significant differences in bleeding events or overall mortality occurred between the groups. Recent recommendations from the American College of Chest Physicians on the treatment of cancer-associated thrombosis are based in part on data from the CLOT trial and support the use of dalteparin and tinzaparin in the long-term treatment of patients with DVT and cancer. Finally, results of recent trials support the concept that antithrombotic therapy with dalteparin or nadroparin may have an antineoplastic effect, resulting in improved survival time. However, these results require further validation. Conclusion. Despite the absence of oncology-specific guidelines for cancer-associated thrombosis, pharmacists now have a number of new tools available for selecting an anticoagulant, including results from several clinical trials with LMWHs and recent reports from national meetings.

Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients With Cancer and Venous Thromboembolism

Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism. Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups. During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02). The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.

Self-management of anticoagulation therapy after mechanical heart valve replacement -10 years experience of a single center

Objectives: Oral anticoagulation (OA) requires frequent blood-checks and dose-changes to prevent thromboembolic or hemorrhagic complications after mechanical heart valve (MHV) replacement. We hypothesize that quality of OA and long-term outcome of patients with self-management of OA (group 1) is superior to conventional anticoagulation treatment (group 2).

Long‐term low‐dose warfarin use is effective in the prevention of recurrent venous thromboembolism: no

Long‐term low‐dose warfarin use is effective in the prevention of recurrent venous thromboembolism: no

Low-Molecular-Weight Heparin Versus Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer

Patients with cancer have a substantial risk of recurrent thromboembolism and hemorrhage when they received standard oral anticoagulant therapy for the treatment and prevention of acute venous thromboembolism. The authorsperformed a six-month, multicenter, randomized open-label clinical trial to investigate whether low-molecular-weight heparin is a safe and effective therapy in preventing recurrent thromboembolism in this group of patients. Cancer patients with deep vein thrombosis, pulmonary embolism, or both, were randomly assigned to receive (1) low-molecular-weight heparin subcutaneously and a coumarin derivative for 6 months (336 patients), or (2) the low-molecular-weight heparin alone for 6 months (336 patients). In the oral anticoagulation group, 53 of 336 patients had recurrent venous thromboembolism, compared with 27 of 336 patients in the low-molecular-weight heparin group. No significant difference was detected between the groups in the rate of bleeding. The low-molecular-weight heparin group had a lower mortality rate (39%) than the oral anticoagulation group (41%). The authors concluded that low-molecular-weight heparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism and did not increase the risk of bleeding.

Cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery

Purpose: Several antithrombotic therapies are available for the treatment of patients with peripheral vascular diseases. It is unknown how quality of life and costs of treatment are influenced by different therapies. This study assessed the cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery. Methods: Clinical outcome events and event-free survival were collected from 2650 patients in 77 centers who participated in the Dutch Bypass Oral anticoagulants or Aspirin trial. Approximately half the patients had critical ischemia; 60% received vein grafts, and 20% had femorocrural bypass grafts. A model that was primarily driven by clinical outcome events was used as a means of determining quality of life (EuroQol EQ-5D) and costs for each patient. The main outcome measure was the incremental health care costs in relation to the additional number of quality-adjusted life years and the additional number of event-free years. Results: The mean costs during the 21 months of follow-up were ϵ 6875 per patient in the oral anticoagulants group versus ϵ 7072 in the aspirin group (difference, 197; 95% CI, –746 to 343). The event-free survival was 1.10 years in the group treated with oral anticoagulants versus 1.09 years in the group treated with aspirin (difference, 0.01; 95% CI, –0.07 to 0.08), whereas the corresponding quality-adjusted life years were 1.06 and 1.05, respectively (difference, 0.01; 95% CI, –0.03 to 0.06). Conclusion: Health care costs, event-free survival, and quality-adjusted life years in patients after infrainguinal bypass surgery were not different in patients treated with aspirin and patients treated with oral anticoagulants. The extra costs of monitoring patients treated with oral anticoagulants were limited and play no role in the decision for treatment. (J Vasc Surg 2001;34:254-62.)

Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis

Purpose: The purpose of this study was to evaluate whether low molecular weight heparin (LMWH) could be equal or more effective than conventional oral anticoagulants (OAs) in the long-term treatment of deep venous thrombosis (DVT). Methods: One hundred fifty-eight patients with symptomatic DVT of the lower limbs confirmed by means of duplex ultrasound scan were randomized to receive 3 to 6 months' treatment with nadroparine calcium or acenocoumarol. Quantitative and qualitative duplex scan scoring systems were used to study the evolution of thrombosis in both groups at 1, 3, 6, and 12 months. Results: During the 12-month surveillance period, two (2.5%) of the 81 patients who received LMWH and seven (9%) of the 77 patients who received OAs had recurrence of venous thrombosis (not significant). In the LMWH group no cases of major bleeding were found, and four cases (5.2%) occurred in the OA group (not significant). The mortality rate was nine (11.1%) in the LMWH group and 7.8% in the OA group (not significant). The quantitative mean duplex scan score decreased in both groups during the follow-up and had statistical significance after long-term LMWH treatment on iliofemoral DVT (1, 3, 6, and 12 months), femoropopliteal DVT (1-3 months), and infrapopliteal DVT (first month). Duplex scan evaluation showed that the rate of venous recanalization significantly increased in the common femoral vein at 6 and at 12 months and during each point of follow-up in the superficial and popliteal veins in the LMWH group. Reflux was significantly less frequent in communicating veins after LMWH treatment (17.9% vs 32.2% in the OA group). The reflux rates in the superficial (22.4% in the LMWH group, 30.6% in OA group) and deep (13.4% vs 17.7%) venous system showed no significant differences between groups. Conclusions: The unmonitored subcutaneous administration of nadroparine in fixed daily doses was more effective than oral acenocoumarol with laboratory control adjustment in achieving recanalization of leg thrombi. With nadroparine, there was less late valvular communicating vein insufficiency, and it was at least as efficacious and safe as oral anticoagulants after long-term administration. These results suggest that LMWHs may therefore represent a real therapeutic advance in the long-term management of DVT. (J Vasc Surg 2001;33:77-90.)

Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral anticoagulants or Aspirin study): a randomised trial

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.

Low Molecular Weight Heparin versus Acenocoumarol in the Secondary Prophylaxis of Deep Vein Thrombosis

The aim of this study was to determine the efficacy and safety of subcutaneous weight-adjusted dose low molecular weight heparin (LMWH) compared with oral anticoagulant (OA) in the prevention of recurrent venous thromboembolism. In a prospective multicenter trial, 202 patients with symptomatic proximal deep vein thrombosis (DVT) were included. As soon as the diagnosis of DVT was confirmed by phlebography, 101 were randomly assigned to receive LMWH (nadroparin) for secondary prophylaxis and 101 to receive OA (acenocoumarol). Patients in both groups were initially treated with nadroparin in a dose of 85 anti-Xa IU/kg s.c. every 12 h. Secondary prophylaxis with either nadroparin, 85 anti-Xa IU/kg s. c. once daily, or acenocoumarol was continued for at least 3 months. Three patients in the LMWH group and 6 in the OA group were excluded from analysis for various reasons. During the one-year combined secondary prophylaxis and surveillance period, 7 of of the 98 evaluable patients (7.1%) in the LMWH group and 9 of the 95 evaluable patients (9.5%) in the OA group had a documented recurrence of venous thromboembolism (Fisher's exact test, p = 0.61). Of these, 2 patients who received LMWH and 7 patients on acenocoumarol had recurrences in the 3-month period of secondary prophylaxis. Four patients (4.1%) in the LMWH group developed bleeding complications during this study period, as compared with 7 (7.4%) in the OA group (Fisher's exact test, p = 0.37). There were two major bleedings, one in the LMWH group and one in the OA group. Eleven patients died, 5 (5.1%) in the LMWH group and 6 (6.3%) in the OA group. It is concluded that nadroparin in a dose of 85 anti-Xa IU/kg s.c. once daily provides an effective and safe alternative to oral anticoagulants in the secondary prophylaxis of DVT.

Effects of low dose aspirin (50 mg/day), low dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass grafting: Patency and clinical outcome at 1 year

Objectives. This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anti-coagulant agents in the prevention of internal mammary artery graft occlusion.Background. Antithrombotic drugs increase vein graft patency after coronary artery bypass surgery. Their benefit after internal mammary artery grafting has not been established.Methods. 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.Results. 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.Conclusions. 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.

Oral Anticoagulant Therapy Recommendations

Oral Anticoagulant Therapy Recommendations

Prevention of one-year vein-graft occlusion after aortocoronary- bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants

Summary 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% Cl 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% Cl 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.

A Novel Functional Assay of Protein C in Human Plasma and fts Comparison with Amidolytic and Anticoagulant Assays

A simple and fast method for the quantitative determination of protein C activity in plasma is here described. The first step consists in the conversion of protein C in the test sample into activated protein C by means of an activator isolated from Southern Copperhead venom. Subsequently, the degradation of factor Va, in presence of protein C-deficient plasma, is measured by the prolongation of the prothrombin time which is proportional to the amount of protein C in the sample. The dose-response curve showed a linear relationship from 6 to 150% protein C activity and the inter- and intra-assay reproducibility was 3.5% and 5.6% respectively. In normal subjects, a mean of protein C level of 98 +/- 15% of normal pooled plasma was found. Comparison with the anticoagulant assay in samples of patients with oral anticoagulant, liver cirrhosis, disseminated intravascular coagulation and severe preeclampsia revealed an excellent correlation (r = 0.94, p less than 0.001). Also, a similar correlation (r = 0.93, p less than 0.001) existed between amidolytic assay and the method here proposed for all the samples studied without including the oral anticoagulant group. These results allowed us to infer that this method evaluates the ability of protein C to interact with protein S, phospholipids, calcium ions and factor Va.

Local hemostasis after tooth extraction in patients with abnormal hemostatic function. Use of human fibrinogen concentrate.

Tooth extraction was carried out in 405 patients with various hemostatic disorders due to thrombocytopenia, chronic liver disease, hemophilia A and B, von Willebrand's disease and oral anticoagulants. Human fibrinogen concentrate was used as local hemostatic agent. Prophylactic replacement therapy (platelets or plasma concentrates) and antifibrinolytic agents were not administered. Oral anticoagulants were not discontinued. Minor postextraction bleeding occurred only in severe hemophilia A and occasionally in the oral anticoagulant group.

ORAL ANTICOAGULANTS CONTROLLED BY THE BRITISH COMPARATIVE THROMBOPLASTIN VERSUS LOW-DOSE HEPARIN IN PROPHYLAXIS OF DEEP VEIN THROMBOSIS

The British comparative thromboplastin (BCT) was used to monitor the effectiveness of oral anticoagulants in preventing deep vein thrombosis (DVT) in patients undergoing major gynaecological surgery. All patients were screened for DVT with the use of the 125I-fibrinogen scan. One hundred and forty-five patients aged 40 years or more were randomised into three groups. Group 1 received oral anticoagulant (nicoumalone) treatment, stabilised over five days before surgery and continuing into the second postoperative week. The other patients served as two contrast groups and were managed on a double-blind basis. Group 2 received a subcutaneous low-dose regimen of heparin calcium. Group 3 received subcutaneous saline. Eleven of 48 patients in the saline group, three of 49 patients in the heparin group, and three of 48 patients in the oral anticoagulant group developed DVT as judged by 125I-fibrinogen scanning. The incidences in groups 1 and 2 were significantly lower than in the saline group. The falls in haemoglobin concentration and incidence of haemorrhage were similar in all three groups. The study showed that oral anticoagulant prophylaxis stabilised preoperatively and low-dose heparin were equally effective in preventing deep vein thrombosis in a moderate-risk group. Immediate preoperative prothrombin ratios of 2·0-2·5 and postoperative ratios of 2·0-4·0 with the BCT gave adequate protection without increased haemorrhagic risk.

Oral anticoagulants controlled by the British comparative thromboplastin versus low-dose heparin in prophylaxis of deep vein thrombosis

The British comparative thromboplastin (BCT) was used to monitor the effectiveness of oral anticoagulants in preventing deep vein thrombosis (DVT) in patients undergoing major gynaecological surgery. All patients were screened for DVT with the use of the (125)I-fibrinogen scan.One hundred and forty-five patients aged 40 years or more were randomised into three groups. Group 1 received oral anticoagulant (nicoumalone) treatment, stabilised over five days before surgery and continuing into the second postoperative week. The other patients served as two contrast groups and were managed on a double-blind basis. Group 2 received a subcutaneous low-dose regimen of heparin calcium. Group 3 received subcutaneous saline. Eleven of 48 patients in the saline group, three of 49 patients in the heparin group, and three of 48 patients in the oral anticoagulant group developed DVT as judged by (125)I-fibrinogen scanning. The incidences in groups 1 and 2 were significantly lower than in the saline group. The falls in haemoglobin concentration and incidence of haemorrhage were similar in all three groups.The study showed that oral anticoagulant prophylaxis stabilised preoperatively and low-dose heparin were equally effective in preventing deep vein thrombosis in a moderate-risk group. Immediate preoperative prothrombin ratios of 2.0-2.5 and postoperative ratios of 2.0-4.0 with the BCT gave adequate protection without increased haemorrhagic risk.