67 research outputs found
Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism : a pooled analysis of the EINSTEIN-DVT and PE randomized studies
Background: Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects.
Methods: A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75.
Results: 8282 patients were enrolled. 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 rivaroxaban-treated patients (2.1%) compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66-1.19; pnoninferiority<0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37-0.79; p=0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban was similar compared with standard-therapy.
Conclusion: The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups
Apixaban for extended treatment of venous thromboembolism
Background: Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. Methods: in this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. Results: a total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. Conclusions: extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893)
Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score
Aims
Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation.
Methods and results
Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding.
Conclusion
The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making
Edoxaban for stroke prevention in atrial fibrillation and treatment of venous thromboembolism: an expert position paper
Diagnosis of pulmonary embolism
The clinical diagnosis of pulmonary embolism is highly nonspecific because none of the symptoms or signs of pulmonary embolism is unique and all may be caused by other cardiorespiratory disorders. Thus, objective testing is mandatory to either confirm or exclude a diagnosis of pulmonary embolism. Based on current available information, a diagnostic approach for the management of clinically suspected pulmonary embolism is proposed. After a history and physical examination, electrocardiogram and chest X-ray film, all patients should undergo perfusion lung scanning. The finding of a normal perfusion lung scan rules out clinically significant pulmonary embolism, and anticoagulant therapy is withheld.The management of patients with an abnormal perfusion lung scan is more complex. If this scan demonstrates one or more segmental (or greater) perfusion defects, ventilation lung scanning should be performed because the probability of pulmonary embolism is markedly increased if a mismatch is found, with a high probability scan (positive predictive value 86 %) providing an end point for commencing anticoagulant therapy in the majority of patients. In an abnormal ventilationperfusion study, the presence of a ventilation-perfusion match does not rule out the possibility of pulmonary embolism, and further objective testing is required in these patients with nonhigh probability scans. Similarly, in patients with small perfusion defects (one or more subsegmental defects) or indeterminate lung scan findings (in which the perfusion scan defects correspond to a defect on a chest X-ray film), the predictive values obtained from these ventilation-perfusion scan patterns are not sufficiently high or low to confirm or exclude the presence of pulmonary embolism.Alternative approaches are available that would reduce the need for pulmonary angiography in patients with abnormal but nonhigh probability ventilationperfusion lung scans. In these patients, venography or impedance plethysmography could be performed as the next step of the diagnostic evaluation. If the presence of deep vein thrombosis is confirmed by these tests, anticoagulant therapy can be commenced without the need to perform pulmonary angiography. If the tests are negative, pulmonary angiography is required to confirm the presence or absence of pulmonary embolism because a negative venogram occurs in up to 30% of patients with pulmonary embolism by angiography and, therefore, may not be used to exclude venous thromboembolism. Other approaches (for example, serial impedance plethysmography) are being explored in selected patients
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