Extended prophylaxis for venous thromboembolism after hospitalization for medical illness: A trial sequential and cumulative meta-analysis

Figures

• 

  Fig 1. Flow diagram for study selection. MeSH, Medical Subject Headings.

• 

  Fig 2. 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). 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…

• 

  Fig 3. Forest plot for cumulative meta-analysis of EDT versus standard-duration thromboprophylaxis in hospitalized medically ill patients for primary efficacy events. 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…

• 

  Fig 4. Trial sequential analysis of EDT versus standard-duration thromboprophylaxis in hospitalized medically ill patients for primary efficacy events. The green dashed line represents Lan–DeMets trial sequential boundary for benefit and the maroon dashed line represents Lan–DeMets trial sequential boundary for harm. The blue solid line is cumulative Z-curve derived from random effects cumulative meta-analysis. The solid bright green line indicates line of no difference, and dashed black lines are upper and lower bounds for 95% CI. The total accrued information size for this analysis was 40,247 patients. The cumulative Z-curve surpassed both the dashed black line (line of statistical significance at Z-score of +1.96) and green dashed line (Lan–DeMets trial sequential boundary for benefit), indicating true benefit EDT over standard of care in reducing postdischarge VTE. 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…

• 

  Fig 5. Forest plot for cumulative meta-analysis of EDT versus standard-duration thromboprophylaxis in hospitalized medically ill patients for major or fatal bleeding. Black solid square markers and associated solid lines represent cumulative summary RR and 95% CI after addition of each trial as listed in 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…

• 

  Fig 6. 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. 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…