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In a large trial, the estimated incidence of stroke, systemic embolism, hemorrhage, or death was 2.8 percentage points lower to 0.5 percentage points higher with early than with later use of direct oral anticoagulants.

In patients with venous thromboembolism at high risk of recurrence for whom extended treatment with direct oral anticoagulants has been indicated, the optimal dose is unknown. We aimed to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in patients in whom extended anticoagulation has been indicated. RENOVE was a non-inferiority, investigator-initiated, multicentre, randomised, open-label, blinded endpoint trial done in 47 hospitals in France. Ambulatory patients aged 18 years or older with acute symptomatic venous thromboembolism (pulmonary embolism or proximal deep vein thrombosis) who had received 6–24 uninterrupted months of full-dose anticoagulation and for whom extended anticoagulation has been indicated were eligible. Eligible participants were categorised as having either a first unprovoked venous thromboembolism, recurrent venous thromboembolism, presence of persistent risk factors, or other clinical situations considered to be a high risk of recurrence. Participants were randomly assigned (1:1) to receive oral treatment with either a reduced dose of apixaban (2·5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily) using a centralised randomisation procedure with an interactive web response system. The sequence generation method was a computerised random number generator and was balanced by blocks of different sizes. Randomisation was stratified by centre, type of direct oral anticoagulant, and antiplatelet drug. Physicians and participants were unmasked to treatment allocation; recurrent venous thromboembolism, clinically relevant bleeding, and all-cause death were adjudicated by an independent committee blinded to treatment allocation. The primary outcome was symptomatic recurrent venous thromboembolism, including recurrent fatal or non-fatal pulmonary embolism or isolated proximal deep vein thrombosis (non-inferiority hypothesis 90% power to exclude a hazard ratio [HR] of 1·7). The primary outcome and first two secondary outcomes were included in a hierarchical testing procedure. This trial is registered with ClinicalTrials.gov, NCT03285438. From Nov 2, 2017, to July 6, 2022, 2768 patients were enrolled and randomly assigned to the reduced-dose group (n=1383) or the full-dose group (n=1385). 970 (35·0%) participants were female, 1797 (65·0%) were male, and one (<0·1%) had sex not reported. Median follow-up was 37·1 months (IQR 24·0–48·3). Recurrent venous thromboembolism occurred in 19 of 1383 patients in the reduced-dose group (5-year cumulative incidence 2·2% [95% CI 1·1–3·3]) versus 15 of 1385 patients in the full-dose group (5-year cumulative incidence 1·8% [0·8–2·7]; adjusted HR 1·32 [95% CI 0·67–2·60]; absolute difference 0·40% [95% CI –1·05 to 1·85]; p=0·23 for non-inferiority). Major or clinically relevant bleeding occurred in 96 patients in the reduced-dose group (5-year cumulative incidence 9·9% [95% CI 7·7–12·1]) and 154 patients in the full-dose group (5-year cumulative incidence 15·2% [12·8–17·6]; adjusted HR 0·61 [95% CI 0·48–0·79]). 1136 (82·1%) of 1383 patients in the reduced-dose group and 1150 (83·0%) of 1385 in the full-dose group had an adverse event; 374 (27·0%) patients in the reduced-dose group and 420 (30·3%) in the full-dose group has a serious adverse event. 35 (5-year cumulative incidence 4·3% [95% CI 2·6–6·0]) patients in the reduced-dose group and 54 (5-year cumulative incidence 6·1% [4·3–8·0]) patients in the full-dose group died during the study period. In patients with venous thromboembolism requiring extended anticoagulation, reduction of the direct oral anticoagulant dose did not meet the non-inferiority criteria. However, the low recurrence rates in both groups and substantial reduction of clinically relevant bleeding with the reduced dose could support this regimen as an option. Further research will be needed to identify subgroups for whom the anticoagulation dose should not be reduced. French Ministry of Health.

In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem. Acute venous thromboembolism (i.e., deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. 1 , 2 Short-term treatment is effective, with the risk of recurrent disease — the major complication — reduced from an estimated 25% to about 3% during the first 6 to 12 months of therapy. 3 The risk of recurrence remains after treatment ends and can reach 5 to 10% during the first year. 4 , 5 Standard treatment for acute venous thromboembolism is limited by the need for parenteral heparin initially, with overlapping . . .

In the treatment of patients with acute pulmonary embolism, the efficacy of rivaroxaban, a factor Xa inhibitor, was similar to that of traditional anticoagulation therapy. There was less bleeding in the group receiving rivaroxaban, which supports its use in the treatment of this condition. Pulmonary embolism is a common disease, with an estimated annual incidence of 70 cases per 100,000 population. 1 , 2 The condition usually leads to hospitalization and may recur; it can be fatal. 3 For half a century, the standard therapy for most patients with pulmonary embolism has been the administration of heparin, overlapped and followed by a vitamin K antagonist. 4 , 5 This regimen is effective but complex. 5 – 9 Recently developed oral anticoagulants that are directed against factor Xa or thrombin overcome some limitations of standard therapy, including the need for injection and for regular dose adjustments on the basis of laboratory monitoring. . . .

Rivaroxaban is an orally administered direct inhibitor of factor Xa. As compared with enoxaparin, rivaroxaban was more effective in preventing venous thromboembolism after hip replacement, without a significant increase in major bleeding. Rivaroxaban is an orally administered direct inhibitor of factor Xa. As compared with enoxaparin, rivaroxaban was more effective in preventing venous thromboembolism after hip replacement, without a significant increase in major bleeding. Prophylactic anticoagulant therapy is standard practice after total hip or knee arthroplasty, with a minimum recommended duration of 10 days. 1 After total hip arthroplasty, extended prophylaxis for 5 weeks after surgery reduces the incidence of symptomatic and asymptomatic venous thromboembolism more effectively than does short-term prophylaxis. 2 New deep-vein thromboses have been shown to form after the discontinuation of short-term prophylaxis. 3 Several meta-analyses suggest that extended thromboprophylaxis after total hip arthroplasty leads to a reduction in symptomatic venous thromboembolic events, without increasing the risk of major bleeding. 4 – 6 These findings led to a grade 1A recommendation for extended thromboprophylaxis after total . . .

Unfractionated heparin and low-molecular-weight heparins are often used to treat acute coronary syndromes. In this study, the pentasaccharide fondaparinux was found to have efficacy equal to that of enoxaparin in terms of anti-ischemic benefits but was associated with substantially less bleeding and lower long-term morbidity and mortality. Fondaparinux was found to have efficacy equal to that of enoxaparin in terms of anti-ischemic benefits but was associated with substantially less bleeding and lower long-term morbidity and mortality. The combined use of anticoagulants, 1 antiplatelet agents, 2 – 4 and an invasive strategy 5 in high-risk patients with acute coronary syndromes reduces ischemic coronary events but also increases bleeding. Bleeding may increase the risk of death, 6 myocardial infarction, and stroke. Therefore, future therapies should either preserve or enhance benefits without increasing bleeding. Unfractionated heparin and low-molecular-weight heparins are commonly used in patients with acute coronary syndromes, but enoxaparin may be modestly superior to unfractionated heparin in reducing the risk of death or myocardial infarction. 7 Fondaparinux (Arixtra, GlaxoSmithKline), a synthetic pentasaccharide, selectively binds antithrombin and causes rapid and predictable inhibition of factor Xa. . . .

In a randomized trial involving patients with subclinical (typically asymptomatic) atrial fibrillation, apixaban led to a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding.

In a randomized trial, patients with severe Covid-19 were assigned to receive either therapeutic-dose anticoagulation or usual-care pharmacologic thromboprophylaxis. At 21 days, therapeutic-dose anticoagulation did not improve hospital survival or the number of days free of cardiovascular or respiratory organ support.

In a randomized trial, patients with moderately severe Covid-19 were assigned to receive either therapeutic-dose anticoagulation or usual-care thromboprophylaxis. At 21 days, therapeutic-dose anticoagulation resulted in a higher probability of survival until hospital discharge without organ support.

In a randomized trial, 1050 patients with cancer who had acute venous thromboembolism were assigned to receive either dalteparin or edoxaban for 6 to 12 months. Edoxaban was noninferior to dalteparin with respect to the outcome of recurrent venous thromboembolism or major bleeding.