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Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review.

Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillón E - Vasc Health Risk Manag (2014)

Bottom Line: In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE.Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited.For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.

ABSTRACT
Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE. Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited. For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event.

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Subgroup analysis of major and clinically relevant nonmajor bleeding events depending on index event (PE or DVT) in clinical trials with DOAC in the treatment of VTE.Notes: (A) Initial/long-term therapy versus standard treatment. (B) Extended therapy versus placebo.Abbreviations: AMPLIFY-EXT, Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein; CI, confidence interval; df, degrees of freedom; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; EINSTEIN DVT, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis; EINSTEIN PE, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism; HOKUSAI-VTE, Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots; M-H, Mantel–Haenszel; PE, pulmonary embolism; VTE, venous thromboembolism.
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f4-vhrm-10-627: Subgroup analysis of major and clinically relevant nonmajor bleeding events depending on index event (PE or DVT) in clinical trials with DOAC in the treatment of VTE.Notes: (A) Initial/long-term therapy versus standard treatment. (B) Extended therapy versus placebo.Abbreviations: AMPLIFY-EXT, Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein; CI, confidence interval; df, degrees of freedom; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; EINSTEIN DVT, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis; EINSTEIN PE, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism; HOKUSAI-VTE, Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots; M-H, Mantel–Haenszel; PE, pulmonary embolism; VTE, venous thromboembolism.

Mentions: The risk of CRB versus standard treatment was consistent in patients with index PE (RR: 0.90; 95% CI: 0.80–1.02) and index DVT (RR: 0.87; 95% CI: 0.67–1.12) (P for subgroup differences =0.80) (Figure 4A).


Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review.

Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillón E - Vasc Health Risk Manag (2014)

Subgroup analysis of major and clinically relevant nonmajor bleeding events depending on index event (PE or DVT) in clinical trials with DOAC in the treatment of VTE.Notes: (A) Initial/long-term therapy versus standard treatment. (B) Extended therapy versus placebo.Abbreviations: AMPLIFY-EXT, Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein; CI, confidence interval; df, degrees of freedom; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; EINSTEIN DVT, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis; EINSTEIN PE, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism; HOKUSAI-VTE, Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots; M-H, Mantel–Haenszel; PE, pulmonary embolism; VTE, venous thromboembolism.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230169&req=5

f4-vhrm-10-627: Subgroup analysis of major and clinically relevant nonmajor bleeding events depending on index event (PE or DVT) in clinical trials with DOAC in the treatment of VTE.Notes: (A) Initial/long-term therapy versus standard treatment. (B) Extended therapy versus placebo.Abbreviations: AMPLIFY-EXT, Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein; CI, confidence interval; df, degrees of freedom; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; EINSTEIN DVT, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis; EINSTEIN PE, Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism; HOKUSAI-VTE, Comparative Investigation of Low Molecular Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots; M-H, Mantel–Haenszel; PE, pulmonary embolism; VTE, venous thromboembolism.
Mentions: The risk of CRB versus standard treatment was consistent in patients with index PE (RR: 0.90; 95% CI: 0.80–1.02) and index DVT (RR: 0.87; 95% CI: 0.67–1.12) (P for subgroup differences =0.80) (Figure 4A).

Bottom Line: In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE.Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited.For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.

ABSTRACT
Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE. Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited. For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event.

Show MeSH
Related in: MedlinePlus