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Samuel Z Goldhaber - One of the best experts on this subject based on the ideXlab platform.

  • Extended duration venous thromboembolism prophylaxis with Betrixaban for patients re-admitted with venous thromboembolism
    Journal of Thrombosis and Thrombolysis, 2021
    Co-Authors: Monica Fahmy, Katelyn W. Sylvester, Mattia Migliore, Tewodros Eguale, John Fanikos, Jean M. Connors, Samuel Z Goldhaber
    Abstract:

    Patients hospitalized for an acute medical illness remain at risk of developing venous thromboembolism (VTE) post-discharge. Betrixaban, an oral direct Factor Xa inhibitor, is approved for extended VTE thromboprophylaxis in acutely ill medical patients. The primary objective of this study was to evaluate patients re-admitted with VTE within 30 days of discharge to determine if they would have been eligible for extended duration VTE prophylaxis during the index admission. We used three different sets of eligibility criteria: the APEX study criteria, the Bevyxxa® (Betrixaban) package insert, and Mass General Brigham HealthCare System’s Center for Drug Policy Guidelines. A secondary aim was to describe the reasons for ineligibility. Within 30 days of the index hospital admission, 226 patients were re-admitted with new VTE between January 2017 and December 2018. Of these, 134 (59%) were excluded based on pre-defined exclusion criteria. Of the remaining 92, 22 patients (23.9%) were eligible based on the APEX study criteria, 26 patients (28.2%) based on Mass General Brigham HealthCare System’s Center for Drug Policy Guidelines, and 92 patients (100%) based on the Bevyxxa® package insert. There were 22 patients (23.9%) who were eligible for VTE prophylaxis with Betrixaban based on all three criteria. Appropriate Betrixaban use may have prevented some of the VTE events and re-admissions that occurred within 30 days of initial hospital discharge.

  • Net-clinical benefit of extended prophylaxis of venous thromboembolism with Betrixaban in medically ill patients aged 80 or more.
    Journal of Thrombosis and Haemostasis, 2019
    Co-Authors: Walter Ageno, Samuel Z Goldhaber, Adrian F Hernandez, C. Michael Gibson, Megan K. Yee, Russell D Hull, Renato D. Lopes, Alexander T. Cohen
    Abstract:

    BACKGROUND Extended-duration thromboprophylaxis with Betrixaban reduces the risk of venous thromboembolism (VTE) without increasing major bleeding rates in acutely ill medical patients as compared to standard duration enoxaparin. We aimed to assess the risk-benefit of Betrixaban in patients aged ≥ 80 years enrolled in the APEX trial. METHODS APEX was a randomized, double-blind trial in which patients hospitalized for acute medical illnesses received enoxaparin 40 mg qd for 10 ± 4 days or oral Betrixaban 80 mg qd for 35 to 42 days. The primary efficacy outcome was VTE, the principal safety outcome was major bleeding. Net clinical benefit (NCB) was defined by the occurrence of VTE or major bleeding. RESULTS Of 7513 patients enrolled in the APEX trial, 2781 (37%) were aged ≥ 80 years. In this subgroup, VTE or major bleeding occurred in 7.0% of Betrixaban patients and in 8.4% of enoxaparin patients, for a relative risk in the NCB of 0.82 (95% confidence interval 0.62-1.10). The relative risk reduction obtained with Betrixaban was similar between those aged ≥ 80 years and patients younger than 80 years (5.0% and 6.7%, respectively, NCB 0.75, 0.58-0.96, P = .024), with no significant interaction across age groups (P = .33). CONCLUSIONS Event rates were higher in medically ill patients aged ≥ 80 years enrolled in the APEX study than in patients younger than 80 years. The predefined NCB was reduced with extended Betrixaban therapy in both groups with no signs of age-related interactions. However, the primary efficacy endpoint was not achieved with Betrixaban for patients 80 years of age or older.

  • NNT to prevent one symptomatic VTE or VTE-related death and NNH to cause one major or fatal bleeding event for individual trials and overall pooled estimates.
    2019
    Co-Authors: Navkaranbir S. Bajaj, Samuel Z Goldhaber, Muthiah Vaduganathan, Arman Qamar, Kartik Gupta, Ankur Gupta, Harsh Golwala, Javed Butler, Mandeep R. Mehra
    Abstract:

    The size of red bubbles is proportional to number of patients in the trial, and the size of the black bubble is proportional to accrued information size. The overall pooled estimates for NNH and NNT were calculated by conducting random effects meta-analyses for risk difference for primary efficacy and safety events. Safer implies higher NNH for causing one major or fatal bleeding event. Efficacious implies lower NNT to prevent one symptomatic VTE or VTE-related death. ADOPT, Apixaban Dosing to Optimize Protection from Thrombosis; APEX, Acute Medically Ill Venous Prevention with Extended Duration Betrixaban; EXCLAIM, Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization; MAGELLAN, Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin; MARINER, Medically Ill Patient Assessment of Rivaroxaban versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk; NNH, number need to harm; NNT, number needed to treat; VTE, venous thromboembolism.

  • Forest plot for cumulative meta-analysis of EDT versus standard-duration thromboprophylaxis in hospitalized medically ill patients for primary efficacy events.
    2019
    Co-Authors: Navkaranbir S. Bajaj, Samuel Z Goldhaber, Muthiah Vaduganathan, Arman Qamar, Kartik Gupta, Ankur Gupta, Harsh Golwala, Javed Butler, Mandeep R. Mehra
    Abstract:

    Black solid square markers and associated solid lines represent cumulative summary RR and 95% CI after addition of each trial as listed in the left column. The size of black markers is proportional to total accrued size. The numerical estimates in the right columns are cumulative RRs and 95% CI after sequentially adding each trial and cumulative sample size after addition of each trial listed in left column. ADOPT, Apixaban Dosing to Optimize Protection from Thrombosis; APEX, Acute Medically Ill Venous Prevention with Extended Duration Betrixaban; CI, confidence interval; EDT, extended-duration thromboprophylaxis; EXCLAIM, Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization; MAGELLAN, Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin; MARINER, Medically Ill Patient Assessment of Rivaroxaban versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk; RR, risk ratio.

  • Forest plot comparing EDT versus standard-duration thromboprophylaxis in hospitalized medically ill patients for the primary efficacy endpoint (symptomatic VTE or VTE-related death) and the primary safety endpoint (major or fatal bleeding).
    2019
    Co-Authors: Navkaranbir S. Bajaj, Samuel Z Goldhaber, Muthiah Vaduganathan, Arman Qamar, Kartik Gupta, Ankur Gupta, Harsh Golwala, Javed Butler, Mandeep R. Mehra
    Abstract:

    Black solid square markers and associated solid lines represent summary RR and 95% CI of each trial listed in the left column. The size of black markers is proportional to standard error of effect estimate. The numerical estimates in the right columns are RRs with 95% CI of each trial listed in the left column. The hollow blue diamond is summary RR and 95% CI for VTE or VTE-related death, whereas the hollow red diamond is summary RR for major or fatal bleeding. ADOPT, Apixaban Dosing to Optimize Protection from Thrombosis; APEX, Acute Medically Ill Venous Prevention with Extended Duration Betrixaban; BID, two times a day; CI, confidence interval; EDT, extended-duration thromboprophylaxis; EXCLAIM, Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization; MAGELLAN, Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin; MARINER, Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk; OD, once daily; RR, risk ratio; VTE, venous thromboembolism.

Adrian F Hernandez - One of the best experts on this subject based on the ideXlab platform.

  • Net-clinical benefit of extended prophylaxis of venous thromboembolism with Betrixaban in medically ill patients aged 80 or more.
    Journal of Thrombosis and Haemostasis, 2019
    Co-Authors: Walter Ageno, Samuel Z Goldhaber, Adrian F Hernandez, C. Michael Gibson, Megan K. Yee, Russell D Hull, Renato D. Lopes, Alexander T. Cohen
    Abstract:

    BACKGROUND Extended-duration thromboprophylaxis with Betrixaban reduces the risk of venous thromboembolism (VTE) without increasing major bleeding rates in acutely ill medical patients as compared to standard duration enoxaparin. We aimed to assess the risk-benefit of Betrixaban in patients aged ≥ 80 years enrolled in the APEX trial. METHODS APEX was a randomized, double-blind trial in which patients hospitalized for acute medical illnesses received enoxaparin 40 mg qd for 10 ± 4 days or oral Betrixaban 80 mg qd for 35 to 42 days. The primary efficacy outcome was VTE, the principal safety outcome was major bleeding. Net clinical benefit (NCB) was defined by the occurrence of VTE or major bleeding. RESULTS Of 7513 patients enrolled in the APEX trial, 2781 (37%) were aged ≥ 80 years. In this subgroup, VTE or major bleeding occurred in 7.0% of Betrixaban patients and in 8.4% of enoxaparin patients, for a relative risk in the NCB of 0.82 (95% confidence interval 0.62-1.10). The relative risk reduction obtained with Betrixaban was similar between those aged ≥ 80 years and patients younger than 80 years (5.0% and 6.7%, respectively, NCB 0.75, 0.58-0.96, P = .024), with no significant interaction across age groups (P = .33). CONCLUSIONS Event rates were higher in medically ill patients aged ≥ 80 years enrolled in the APEX study than in patients younger than 80 years. The predefined NCB was reduced with extended Betrixaban therapy in both groups with no signs of age-related interactions. However, the primary efficacy endpoint was not achieved with Betrixaban for patients 80 years of age or older.

  • extended duration Betrixaban versus shorter duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients an apex trial substudy
    Intensive Care Medicine, 2019
    Co-Authors: Gerald Chi, Alexander T. Cohen, Adrian F Hernandez, Arzu Kalayci, Mehrian Jafarizade, Russell D Hull, Michael C Gibson, Farima Kahe, Sadaf Sharfaei, Yuyin Liu
    Abstract:

    To assess the efficacy and safety of Betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients. The APEX trial randomized 7513 acutely ill hospitalized patients to Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35–42 days and at 77 days. At 35–42 days, extended Betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received Betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39). Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration Betrixaban had fewer VTE without more major bleeding events. The benefit of Betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies. http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

  • extended duration Betrixaban reduces the risk of rehospitalization associated with venous thromboembolism among acutely ill hospitalized medical patients findings from the apex trial acute medically ill venous thromboembolism prevention with extended duration Betrixaban trial
    Circulation, 2018
    Co-Authors: Gerald Chi, Alexander T. Cohen, Samuel Z Goldhaber, Adrian F Hernandez, Robert A. Harrington, Megan K. Yee, Russell D Hull, Alpesh Amin, Michael C Gibson
    Abstract:

    Among hospitalized medically ill patients who are at risk of venous thromboembolism (VTE), pharmacological thromboprophylaxis is recommended during the period of immobilization or acute hospital stay.1 However, the risk of VTE extends beyond the standard 10- to 14-day course of anticoagulation and persists for weeks to months after hospital discharge. About half of VTE events occur after the period of index hospitalization and may require rehospitalization.2 Rehospitalization is an end point that adversely affects the morbidity and quality of life of patients and can be a major driver of healthcare costs. Indeed, a goal of patient-centered care is to be both alive and free of hospitalization. The APEX trial (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban Trial; ClinicalTrials.gov: NCT01583218) was a double-blind randomized clinical trial that compared extended-duration (35–42 days) Betrixaban with standard-duration (10±4 days) enoxaparin among acutely ill hospitalized medical patients at increased risk of VTE. A reduction in VTE by extended-duration Betrixaban compared with standard-duration enoxaparin has been demonstrated,3 but the impact of extended thromboprophylaxis with Betrixaban on the risk of rehospitalization associated with VTE has not been studied. It was hypothesized that Betrixaban would reduce VTE-related rehospitalization. The APEX trial randomized 7513 patients to either extended-duration Betrixaban or standard-duration enoxaparin for VTE prophylaxis. The full-dose regimen (Betrixaban 80 mg daily) was administered to patients who had a creatinine clearance of ≥30 mL/min and were not administered a strong P-glycoprotein inhibitor. VTE-related rehospitalization was …

  • increased benefit of Betrixaban among patients with a history of venous thromboembolism a post hoc analysis of the apex trial
    Journal of Thrombosis and Thrombolysis, 2018
    Co-Authors: Megan K. Yee, Samuel Z Goldhaber, Adrian F Hernandez, Tarek Nafee, Fahad Alkhalfan, Serge Korjian, Yazan Daaboul, Mathieu Kerneis, Cara Wiest, Russell D Hull
    Abstract:

    Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of Betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of Betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06–5.30, p 0.05). Additionally, four subjects in the enoxaparin arm and one subject in the Betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, Betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41–0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36–0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with Betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis.

  • Increased benefit of Betrixaban among patients with a history of venous thromboembolism: a post-hoc analysis of the APEX trial
    Journal of Thrombosis and Thrombolysis, 2018
    Co-Authors: Tarek Nafee, Samuel Z Goldhaber, Adrian F Hernandez, Fahad Alkhalfan, Russell D Hull, Serge Korjian, Yazan Daaboul, Mathieu Kerneis, Cara Wiest, Alexander T. Cohen
    Abstract:

    Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of Betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of Betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06–5.30, p  0.05). Additionally, four subjects in the enoxaparin arm and one subject in the Betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, Betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41–0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36–0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with Betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis. Trial registration: http://www.clinicaltrials.gov , Unique identifier: NCT01583218

Alexander T. Cohen - One of the best experts on this subject based on the ideXlab platform.

  • budget impact analysis of Betrixaban for venous thromboembolism prophylaxis in nonsurgical patients with acute medical illness in the united kingdom
    Expert Review of Pharmacoeconomics & Outcomes Research, 2020
    Co-Authors: Holly Guy, Vicki Laskier, Mark Fisher, Iwona Bucior, Steven Deitelzweig, Alexander T. Cohen
    Abstract:

    Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Service (NHS). Betrixaban is approved in the US for VTE prophylaxis with a recommended 35–42 days of treatment. This ...

  • Net-clinical benefit of extended prophylaxis of venous thromboembolism with Betrixaban in medically ill patients aged 80 or more.
    Journal of Thrombosis and Haemostasis, 2019
    Co-Authors: Walter Ageno, Samuel Z Goldhaber, Adrian F Hernandez, C. Michael Gibson, Megan K. Yee, Russell D Hull, Renato D. Lopes, Alexander T. Cohen
    Abstract:

    BACKGROUND Extended-duration thromboprophylaxis with Betrixaban reduces the risk of venous thromboembolism (VTE) without increasing major bleeding rates in acutely ill medical patients as compared to standard duration enoxaparin. We aimed to assess the risk-benefit of Betrixaban in patients aged ≥ 80 years enrolled in the APEX trial. METHODS APEX was a randomized, double-blind trial in which patients hospitalized for acute medical illnesses received enoxaparin 40 mg qd for 10 ± 4 days or oral Betrixaban 80 mg qd for 35 to 42 days. The primary efficacy outcome was VTE, the principal safety outcome was major bleeding. Net clinical benefit (NCB) was defined by the occurrence of VTE or major bleeding. RESULTS Of 7513 patients enrolled in the APEX trial, 2781 (37%) were aged ≥ 80 years. In this subgroup, VTE or major bleeding occurred in 7.0% of Betrixaban patients and in 8.4% of enoxaparin patients, for a relative risk in the NCB of 0.82 (95% confidence interval 0.62-1.10). The relative risk reduction obtained with Betrixaban was similar between those aged ≥ 80 years and patients younger than 80 years (5.0% and 6.7%, respectively, NCB 0.75, 0.58-0.96, P = .024), with no significant interaction across age groups (P = .33). CONCLUSIONS Event rates were higher in medically ill patients aged ≥ 80 years enrolled in the APEX study than in patients younger than 80 years. The predefined NCB was reduced with extended Betrixaban therapy in both groups with no signs of age-related interactions. However, the primary efficacy endpoint was not achieved with Betrixaban for patients 80 years of age or older.

  • cost effectiveness of Betrixaban compared with enoxaparin for venous thromboembolism prophylaxis in nonsurgical patients with acute medical illness in the united states
    PharmacoEconomics, 2019
    Co-Authors: Holly Guy, Vicki Laskier, Mark Fisher, Richey W Neuman, Iwona Bucior, Steven Deitelzweig, Alexander T. Cohen
    Abstract:

    Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in nonsurgical patients with acute medical illness. Betrixaban is the first anticoagulant approved in the United States (US) for VTE prophylaxis extending beyond hospitalization. The aim was to establish whether Betrixaban for VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the US is cost-effective compared with enoxaparin. A cost-effectiveness analysis was conducted, estimating the cost per quality-adjusted life-year (QALY) gained with Betrixaban (35–42 days) compared with enoxaparin (6–14 days) from a US payer perspective over a lifetime horizon. A decision tree (DT) estimated primary VTE events, thrombotic events, and treatment complications in the first 3 months based on data from the phase III Acute Medically Ill VTE Prevention with Extended Duration Betrixaban study. A Markov model estimated recurrent events and long-term complication risks from published literature. EuroQoL-5 Dimensions utility data and costs inflated to 2017 US dollars (US$) were from published literature. Results were discounted at 3.0% per annum. Deterministic and probabilistic sensitivity analyses explored uncertainty. Betrixaban dominated enoxaparin, with savings of US$784 and increased QALYs of 0.017 per patient. In addition, Betrixaban dominated enoxaparin across all sensitivity analyses, but was most sensitive to utilities and DT probabilities. Furthermore, probabilistic sensitivity analysis found that Betrixaban was more cost-effective than enoxaparin at all willingness-to-pay thresholds. Betrixaban can be considered cost-effective for nonsurgical patients with acute medical illness at risk of VTE, requiring longer VTE prophylaxis from hospitalization through post-discharge.

  • extended duration Betrixaban versus shorter duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients an apex trial substudy
    Intensive Care Medicine, 2019
    Co-Authors: Gerald Chi, Alexander T. Cohen, Adrian F Hernandez, Arzu Kalayci, Mehrian Jafarizade, Russell D Hull, Michael C Gibson, Farima Kahe, Sadaf Sharfaei, Yuyin Liu
    Abstract:

    To assess the efficacy and safety of Betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients. The APEX trial randomized 7513 acutely ill hospitalized patients to Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35–42 days and at 77 days. At 35–42 days, extended Betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received Betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39). Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration Betrixaban had fewer VTE without more major bleeding events. The benefit of Betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies. http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

  • abstract 135 extended thromboprophylaxis with Betrixaban is cost effective in acutely ill medical patients
    Circulation-cardiovascular Quality and Outcomes, 2018
    Co-Authors: Huang Wei, Iwona Bucior, Richey W Neuman, Frederick A Anderson, Alexander T. Cohen
    Abstract:

    Objectives: The APEX trial demonstrated that prophylaxis of venous thromboembolism (VTE) with Betrixaban from hospital admission through post-discharge (35-42 days) in acutely ill medical patients ...

Michael C Gibson - One of the best experts on this subject based on the ideXlab platform.

  • extended duration Betrixaban versus shorter duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients an apex trial substudy
    Intensive Care Medicine, 2019
    Co-Authors: Gerald Chi, Alexander T. Cohen, Adrian F Hernandez, Arzu Kalayci, Mehrian Jafarizade, Russell D Hull, Michael C Gibson, Farima Kahe, Sadaf Sharfaei, Yuyin Liu
    Abstract:

    To assess the efficacy and safety of Betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients. The APEX trial randomized 7513 acutely ill hospitalized patients to Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35–42 days and at 77 days. At 35–42 days, extended Betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received Betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39). Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration Betrixaban had fewer VTE without more major bleeding events. The benefit of Betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies. http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

  • asymptomatic deep vein thrombosis is associated with an increased risk of death insights from the apex trial
    Thrombosis and Haemostasis, 2018
    Co-Authors: Arzu Kalayci, Tarek Nafee, Megan K. Yee, Gerald Chi, Michael C Gibson, Serge Korjian, Sudarshana Datta, Mike Gurin, Noah Q Haroian, Iqra Qamar
    Abstract:

    Aim Asymptomatic deep vein thrombosis (DVT) diagnosed with compression ultrasound (CUS) is a common endpoint in trials assessing the efficacy of anticoagulants to prevent venous thromboembolism (VTE), but the relationship of asymptomatic thrombus to mortality remains uncertain. Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration Betrixaban (35–42 days) or enoxaparin (10 ± 4 days). Asymptomatic DVT was assessed once with CUS between day 32 and 47, and mortality was assessed through 77 days. Results A total of 309 asymptomatic DVTs were detected through CUS. Of these, 133 (4.27%) subjects were in the Betrixaban group, and 176 (5.55%) subjects were in the enoxaparin group (relative risk = 0.77, 95% confidence interval [CI] = 0.62–0.97, p = 0.025, number needed to treat = 79). With respect to all-cause mortality due to cardiovascular diseases, non-cardiovascular diseases and unknown causes, the number of the deaths was 5 (1.67%), 4 (1.34%) and 1 (0.33%) in the asymptomatic DVT group and 25 (0.42%), 33 (0.56%) and 11 (0.19%) in the no DVT group, respectively. Subjects with an asymptomatic DVT had an almost threefold increase in the risk of all-cause mortality compared with subjects without DVT (hazard ratio = 2.87, 95% CI = 1.48–5.57, p = 0.001). A positive linear trend was observed between greater thrombus burden and mortality during the follow-up (p = 0.019). Conclusion Asymptomatic DVT was associated with approximately threefold increased risk of short-term all-cause mortality in patients hospitalized with an acute medical illness within the prior 77 days. A positive linear trend was observed between greater thrombus burden and mortality during the follow-up.

  • symptomatic event reduction with extended duration Betrixaban in acute medically ill hospitalized patients
    American Heart Journal, 2018
    Co-Authors: Michael C Gibson, Samuel Z Goldhaber, Tarek Nafee, Megan K. Yee, Fahad Alkhalfan, Gerald Chi, Serge Korjian, Yazan Daaboul, Mathieu Kerneis, R D Hull
    Abstract:

    Abstract Background Approximately 15%-30% of patients in trials of medical thromboprophylaxis will have missing compression ultrasound (CUS) data. The goal of the present analysis was to perform analyses to minimize missing data. Methods The APEX trial randomized 7,513 acutely medically ill hospitalized patients to thromboprophylaxis with either Betrixaban for 35-42 days or enoxaparin for 6-14 days. A modified intent-to-treat (mITT) analysis was performed and included all subjects administered study drug, irrespective of CUS performance, and an analysis of symptomatic events which do not require performance of a CUS (symptomatic deep vein thrombosis, nonfatal pulmonary embolism, and venous thromboembolism (VTE)–related mortality). Results In the mITT population, Betrixaban significantly reduced the primary end point (which included both symptomatic and CUS events) (165 [4.4%] vs 223 [6.0%]; relative risk = 0.75; 95% CI 0.61-0.91; P = .003; absolute risk reduction [ARR] = 1.6%; number needed to treat [NNT] = 63). Betrixaban also reduced symptomatic VTE through day 42 (35 [1.28%] vs 54 [1.88%], hazard ratio [HR] = 0.65; 95% CI 0.42-0.99; P = .044; ARR = 0.6%; NNT=167) as well as through day 77 (37 [1.02%] vs 67 [1.89%]; HR= 0.55; 95% CI 0.37-0.83; P = .003; ARR = 0.87%; NNT=115) as well as the individual end point of nonfatal pulmonary embolism (9 [0.25%] vs 20 [0.55%]; HR= 0.45; 95% CI 0.21-0.99; P = .041; ARR = 0.30%; NNT=334). On an “as-treated” basis, 80 mg of Betrixaban reduced VTE-related mortality through day 77 (10 [0.34%] vs. 22 [0.79%]; HR=0.46; 95% CI 0.22-0.96; P = .035; ARR = 0.45%; NNT=223). Conclusion In an mITT analysis of all patients administered study drug, extended-duration Betrixaban reduced the primary end point as well as symptomatic events. In an as-treated analysis, 80 mg of Betrixaban reduced VTE-related death.

  • extended duration Betrixaban reduces the risk of rehospitalization associated with venous thromboembolism among acutely ill hospitalized medical patients findings from the apex trial acute medically ill venous thromboembolism prevention with extended duration Betrixaban trial
    Circulation, 2018
    Co-Authors: Gerald Chi, Alexander T. Cohen, Samuel Z Goldhaber, Adrian F Hernandez, Robert A. Harrington, Megan K. Yee, Russell D Hull, Alpesh Amin, Michael C Gibson
    Abstract:

    Among hospitalized medically ill patients who are at risk of venous thromboembolism (VTE), pharmacological thromboprophylaxis is recommended during the period of immobilization or acute hospital stay.1 However, the risk of VTE extends beyond the standard 10- to 14-day course of anticoagulation and persists for weeks to months after hospital discharge. About half of VTE events occur after the period of index hospitalization and may require rehospitalization.2 Rehospitalization is an end point that adversely affects the morbidity and quality of life of patients and can be a major driver of healthcare costs. Indeed, a goal of patient-centered care is to be both alive and free of hospitalization. The APEX trial (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban Trial; ClinicalTrials.gov: NCT01583218) was a double-blind randomized clinical trial that compared extended-duration (35–42 days) Betrixaban with standard-duration (10±4 days) enoxaparin among acutely ill hospitalized medical patients at increased risk of VTE. A reduction in VTE by extended-duration Betrixaban compared with standard-duration enoxaparin has been demonstrated,3 but the impact of extended thromboprophylaxis with Betrixaban on the risk of rehospitalization associated with VTE has not been studied. It was hypothesized that Betrixaban would reduce VTE-related rehospitalization. The APEX trial randomized 7513 patients to either extended-duration Betrixaban or standard-duration enoxaparin for VTE prophylaxis. The full-dose regimen (Betrixaban 80 mg daily) was administered to patients who had a creatinine clearance of ≥30 mL/min and were not administered a strong P-glycoprotein inhibitor. VTE-related rehospitalization was …

  • association of d dimer levels with clinical event rates and the efficacy of Betrixaban versus enoxaparin in the apex trial
    TH open : companion journal to thrombosis and haemostasis, 2018
    Co-Authors: Michael C Gibson, Tarek Nafee, Megan K. Yee, Fahad Alkhalfan, Gerald Chi, Rim Halaby, Serge Korjian, Mathieu Kerneis, Lisa K Jennings, Yazan Daaboul
    Abstract:

    Background Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of Betrixaban versus enoxaparin in the APEX trial. Methods Hospitalized acutely medically ill subjects (n = 7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral Betrixaban (80 mg once daily for 35–42 days) or standard dose subcutaneous enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. Results For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the Betrixaban (p < 0.001) and enoxaparin (p < 0.001) treatment arms. Among D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration Betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [n = 124] vs. 7.6% [n = 170]; odds ratio = 0.69; 95% confidence interval: 0.55–0.88; absolute risk reduction = 2.2%, number needed to treat = 46, p = 0.003). There was no interaction between D-dimer and the treatment effect (p int = 0.53). Conclusion Extended-duration Betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with Betrixaban.

Russell D Hull - One of the best experts on this subject based on the ideXlab platform.

  • Net-clinical benefit of extended prophylaxis of venous thromboembolism with Betrixaban in medically ill patients aged 80 or more.
    Journal of Thrombosis and Haemostasis, 2019
    Co-Authors: Walter Ageno, Samuel Z Goldhaber, Adrian F Hernandez, C. Michael Gibson, Megan K. Yee, Russell D Hull, Renato D. Lopes, Alexander T. Cohen
    Abstract:

    BACKGROUND Extended-duration thromboprophylaxis with Betrixaban reduces the risk of venous thromboembolism (VTE) without increasing major bleeding rates in acutely ill medical patients as compared to standard duration enoxaparin. We aimed to assess the risk-benefit of Betrixaban in patients aged ≥ 80 years enrolled in the APEX trial. METHODS APEX was a randomized, double-blind trial in which patients hospitalized for acute medical illnesses received enoxaparin 40 mg qd for 10 ± 4 days or oral Betrixaban 80 mg qd for 35 to 42 days. The primary efficacy outcome was VTE, the principal safety outcome was major bleeding. Net clinical benefit (NCB) was defined by the occurrence of VTE or major bleeding. RESULTS Of 7513 patients enrolled in the APEX trial, 2781 (37%) were aged ≥ 80 years. In this subgroup, VTE or major bleeding occurred in 7.0% of Betrixaban patients and in 8.4% of enoxaparin patients, for a relative risk in the NCB of 0.82 (95% confidence interval 0.62-1.10). The relative risk reduction obtained with Betrixaban was similar between those aged ≥ 80 years and patients younger than 80 years (5.0% and 6.7%, respectively, NCB 0.75, 0.58-0.96, P = .024), with no significant interaction across age groups (P = .33). CONCLUSIONS Event rates were higher in medically ill patients aged ≥ 80 years enrolled in the APEX study than in patients younger than 80 years. The predefined NCB was reduced with extended Betrixaban therapy in both groups with no signs of age-related interactions. However, the primary efficacy endpoint was not achieved with Betrixaban for patients 80 years of age or older.

  • extended duration Betrixaban versus shorter duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients an apex trial substudy
    Intensive Care Medicine, 2019
    Co-Authors: Gerald Chi, Alexander T. Cohen, Adrian F Hernandez, Arzu Kalayci, Mehrian Jafarizade, Russell D Hull, Michael C Gibson, Farima Kahe, Sadaf Sharfaei, Yuyin Liu
    Abstract:

    To assess the efficacy and safety of Betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients. The APEX trial randomized 7513 acutely ill hospitalized patients to Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35–42 days and at 77 days. At 35–42 days, extended Betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received Betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39). Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration Betrixaban had fewer VTE without more major bleeding events. The benefit of Betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies. http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

  • extended duration Betrixaban reduces the risk of rehospitalization associated with venous thromboembolism among acutely ill hospitalized medical patients findings from the apex trial acute medically ill venous thromboembolism prevention with extended duration Betrixaban trial
    Circulation, 2018
    Co-Authors: Gerald Chi, Alexander T. Cohen, Samuel Z Goldhaber, Adrian F Hernandez, Robert A. Harrington, Megan K. Yee, Russell D Hull, Alpesh Amin, Michael C Gibson
    Abstract:

    Among hospitalized medically ill patients who are at risk of venous thromboembolism (VTE), pharmacological thromboprophylaxis is recommended during the period of immobilization or acute hospital stay.1 However, the risk of VTE extends beyond the standard 10- to 14-day course of anticoagulation and persists for weeks to months after hospital discharge. About half of VTE events occur after the period of index hospitalization and may require rehospitalization.2 Rehospitalization is an end point that adversely affects the morbidity and quality of life of patients and can be a major driver of healthcare costs. Indeed, a goal of patient-centered care is to be both alive and free of hospitalization. The APEX trial (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban Trial; ClinicalTrials.gov: NCT01583218) was a double-blind randomized clinical trial that compared extended-duration (35–42 days) Betrixaban with standard-duration (10±4 days) enoxaparin among acutely ill hospitalized medical patients at increased risk of VTE. A reduction in VTE by extended-duration Betrixaban compared with standard-duration enoxaparin has been demonstrated,3 but the impact of extended thromboprophylaxis with Betrixaban on the risk of rehospitalization associated with VTE has not been studied. It was hypothesized that Betrixaban would reduce VTE-related rehospitalization. The APEX trial randomized 7513 patients to either extended-duration Betrixaban or standard-duration enoxaparin for VTE prophylaxis. The full-dose regimen (Betrixaban 80 mg daily) was administered to patients who had a creatinine clearance of ≥30 mL/min and were not administered a strong P-glycoprotein inhibitor. VTE-related rehospitalization was …

  • Increased benefit of Betrixaban among patients with a history of venous thromboembolism: a post-hoc analysis of the APEX trial
    Journal of Thrombosis and Thrombolysis, 2018
    Co-Authors: Tarek Nafee, Samuel Z Goldhaber, Adrian F Hernandez, Fahad Alkhalfan, Russell D Hull, Serge Korjian, Yazan Daaboul, Mathieu Kerneis, Cara Wiest, Alexander T. Cohen
    Abstract:

    Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of Betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of Betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06–5.30, p  0.05). Additionally, four subjects in the enoxaparin arm and one subject in the Betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, Betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41–0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36–0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with Betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis. Trial registration: http://www.clinicaltrials.gov , Unique identifier: NCT01583218

  • increased benefit of Betrixaban among patients with a history of venous thromboembolism a post hoc analysis of the apex trial
    Journal of Thrombosis and Thrombolysis, 2018
    Co-Authors: Megan K. Yee, Samuel Z Goldhaber, Adrian F Hernandez, Tarek Nafee, Fahad Alkhalfan, Serge Korjian, Yazan Daaboul, Mathieu Kerneis, Cara Wiest, Russell D Hull
    Abstract:

    Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of Betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either Betrixaban for 35–42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of Betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06–5.30, p 0.05). Additionally, four subjects in the enoxaparin arm and one subject in the Betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, Betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41–0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36–0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with Betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis.