Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. Self-management of oral anticoagulation in the elderly: rationale, design, baselines and oral anticoagulation control after one year of follow-up. A randomized controlled trial. Anticoagulant therapy for idiopathic pulmonary fibrosis. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. Optimal Frequency of Patient Monitoring and Intensity of Oral Anticoagulation Therapy in Valvular Heart Disease.
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. This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.
                Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.
                We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.
                Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.
                The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients. Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.
                Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.
                The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).
                Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy. The clinical benefit of coronary-artery stenting performed in conjunction with coronary angioplasty is limited by the risk of thrombotic occlusion of the stent as well as hemorrhagic and vascular complications of intensive anticoagulation. We compared antiplatelet therapy with conventional anticoagulant therapy with respect to clinical outcomes 30 days after coronary-artery stenting.
                After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin). The primary cardiac end point was a composite measure reflecting death from cardiac causes or the occurrence of myocardial infarction, aortocoronary bypass surgery, or repeat angioplasty. The primary noncardiac end point comprised death from noncardiac causes, cerebrovascular accident, severe hemorrhage, and peripheral vascular events.
                Of the patients assigned to antiplatelet therapy, 1.6 percent reached a primary cardiac end point, as did 6.2 percent of those assigned to anticoagulant therapy (relative risk, 0.25; 95 percent confidence interval, 0.06 to 0.77). With antiplatelet therapy, there was an 82 percent lower risk of myocardial infarction than in the anticoagulant-therapy group, and a 78 percent lower need for repeat interventions. Occlusion of the stented vessel occurred in 0.8 percent of the antiplatelet-therapy group and in 5.4 percent of the anticoagulant-therapy group (relative risk, 0.14; 95 percent confidence interval, 0.02 to 0.62). A primary noncardiac end point was reached by 1.2 percent of the antiplatelet-therapy group and 12.3 percent of the anticoagulant-therapy group (relative risk, 0.09; 95 percent confidence interval, 0.02 to 0.31). Hemorrhagic complications occurred only in the anticoagulant-therapy group (in 6.5 percent). An 87 percent reduction in the risk of peripheral vascular events was observed with antiplatelet therapy.
                As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications. Self-management is safe and reliable in patients with long-term oral anticoagulation (OAC). However, no study has yet assessed the safety and efficacy of OAC self-management in elderly patients with major thromboembolic and haemorrhagic complications as primary outcomes. In this multi-centre, open, randomised controlled trial, patients aged 60 years or more were randomised into the self-management group (SMG) (N = 99) or routine care group (RCG) (N = 96). We describe the rationale, design, baseline characteristics and interim analyses of oral anticoagulation control quality within the first year of follow-up. The medians of the squared international normalised ratio (INR) value deviations after six and 12 months were significantly lower in the SMG with medians of 0.16 and 0.16 compared to the RCG with medians of 0.25 and 0.25. The percentage of time within target range and the percentage of INR measurements within target range were significantly higher in the SMG versus the RCG within the first six months (medians 71% vs. 58% and 69% vs. 57%), and during the second six months of the study (75% vs. 67% and 72% vs. 57%). The numbers of all thromboembolic events requiring hospitalisation, major bleeding events, and deaths were similar in both groups. These preliminary results suggest that self-management of oral anticoagulation is safe and feasible for elderly patients willing to participate in a structured training programme. To evaluate the effect of anticoagulant therapy on the survival of patients with idiopathic pulmonary fibrosis (IPF).
                Prospective study.
                Five hospitals located in the Miyagi prefecture in Japan, including a university hospital, a Red Cross hospital, two public general hospitals, and a municipal hospital.
                Fifty-six patients with IPF (mean age, 69.4 years; range, 47 to 89) admitted to the hospitals from April 2001 to April 2004.
                Patients were assigned to receive prednisolone alone or prednisolone plus anticoagulant therapy. The anticoagulants included oral warfarin in an outpatient setting and low-molecular-weight heparin for rehospitalized patients with severely progressive respiratory failure.
                There was no difference in baseline characteristics, including age, gender, clinical condition, pulmonary function, and plasma d-dimer level between the non-anticoagulant group and the anticoagulant group. The overall survival and hospitalization-free periods were assessed. There was a significant difference between survival curves of the non-anticoagulant group and the anticoagulant group, with a 2.9 hazard ratio (p = 0.04, Cox regression model). There was no significant difference in the probability of a hospitalization-free period between groups. The major cause of clinical deterioration was acute exacerbation during follow-up in the present study. Therefore, the mortality and plasma d-dimer levels in patients with an acute exacerbation were also assessed. The mortality associated with acute exacerbations of IPF in the anticoagulant group was significantly reduced compared to that in the non-anticoagulant group (18% vs 71%, respectively; p = 0.008, Fisher Exact Test). Furthermore, the plasma d-dimer levels in patients who died were significantly higher than those in survivors during acute exacerbation of IPF (3.3 +/- 2.3 microg/mL vs 0.9 +/- 0.7 microg/mL, p < 0.0001). Histologic analysis performed in three patients who died due to an exacerbation of IPF in the non-anticoagulant group demonstrated the features of usual interstitial pneumonia and acute lung injury.
                Our data suggested that plasma d-dimer levels are associated with mortality in patients with an acute exacerbation of IPF, and that anticoagulant therapy has a beneficial effect on survival in patients with IPF. Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.
                Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).
                During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.
                In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.
                Copyright 2003 Massachusetts Medical Society To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.
                Randomised controlled trial.
                729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years.
                Primary care in the Netherlands.
                Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2).
                Stroke, systemic embolism, major haemorrhage, and vascular death.
                108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors.
                In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice. The antithrombotic effect of oral anticoagulation therapy and the incidence of anticoagulant-related bleeding complications are both closely correlated with the intensity of treatment. The optimal intensity of oral anticoagulation for an individual patient is the target INR that results in the lowest incidence of thromboembolic plus bleeding complications. For patients with native valve lesions, one must consider the cardiac morphology and pathophysiology, for example, the etiology of the disease, left atrial diameters, loss of active atrial contraction (atrial fibrillation), left ventricular pump function, and left ventricular diameters, to determine an optimal INR target. In patients with prosthetic devices, the "thrombogenicity" of the heart valve prosthesis is an additional risk factor for intracardiac thrombus formation and thromboembolic episodes. This "thrombogenicity" may vary significantly from device to device. INR self-testing improves the overall prognosis of patients on lifelong oral anticoagulation therapy because patients remain more precisely within that target therapeutic INR range. For most patients under phenprocoumon, one to two INR measurements per week are a sufficient frequency to provide a stable intensity of anticoagulation.
Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer while increasing the risk for bleeding.