Abstract
Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.
| Original language | English |
|---|---|
| Pages (from-to) | 677-686 |
| Number of pages | 10 |
| Journal | JAMA - Journal of the American Medical Association |
| Volume | 314 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
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ASJC Scopus subject areas
- Medicine(all)
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Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer : A randomized clinical trial. / CATCH Investigators.
In: JAMA - Journal of the American Medical Association, Vol. 314, No. 7, 01.01.2015, p. 677-686.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer
T2 - A randomized clinical trial
AU - CATCH Investigators
AU - Lee, Agnes Y.Y.
AU - Kamphuisen, Pieter W.
AU - Meyer, Guy
AU - Bauersachs, Rupert
AU - Janas, Mette S.
AU - Jarner, Mikala F.
AU - Khorana, Alok A.
AU - Rafael, Bella Santiago
AU - Susana, Cerana
AU - José, Zarbá Juan
AU - Andel, Johannes
AU - Henrique, Barrios Carlos
AU - André, Borba Reiriz
AU - Fabiane, Cesario
AU - Sérgio, De Azevedo
AU - Fabiano, Ferreira Filho Antonio
AU - André, Franke Fábio
AU - Sergio, Padilha
AU - Renata, Paiva Queiroz
AU - Alex, Pimenta
AU - Júlio, Rerin
AU - Rodrigo, Rigo
AU - Brigitte, Rocha Van Eyll Sylvie
AU - Giuliano, Santos Borges
AU - Giovana, Vacaro
AU - Vasil, Anastasov
AU - Tanya, Dragneva
AU - Georgi, Georgiev
AU - Philip, Champion
AU - Philip, Kuruvilla
AU - Carolina, Gonzalez
AU - Pavel, Ditl
AU - Jiří, Förster
AU - Buncek, Lubomir
AU - Jan, Vydra
AU - Rasha, Abo El Hassan
AU - Sherif, Sabri
AU - Nasr, Allahloubi
AU - Ahmed, Elzawawy
AU - Saad, Ezzat Safwat
AU - Mohamed, Sabry El Kady
AU - Rupert, Bauersachs
AU - Liza, Bacchus
AU - Jan, Beyer Westendorf
AU - Ulrich, Kamphausen
AU - Dietger, Niederwieser
AU - Helmut, Ostermann
AU - Markus, Sosada
AU - Nikolas, Anagnostopoulos
AU - Shin, Sang Won
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.
AB - Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.
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U2 - 10.1001/jama.2015.9243
DO - 10.1001/jama.2015.9243
M3 - Article
C2 - 26284719
AN - SCOPUS:84940649946
VL - 314
SP - 677
EP - 686
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
SN - 0002-9955
IS - 7
ER -