BACKGROUND: The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported. METHODS AND RESULTS: We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001). CONCLUSIONS: Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
RCT Entities:
BACKGROUND: The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported. METHODS AND RESULTS: We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001). CONCLUSIONS: Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
Authors: Renato D Lopes; Richard C Becker; L Kristin Newby; Eric D Peterson; Elaine M Hylek; Christopher B Granger; Mark Crowther; Tracy Wang; Antonio C Carvalho; Otavio Berwanger; Roberto R Giraldez; Gilson Soares Feitosa; Jorge Pinto Ribeiro; Eduardo Darze; Renato A K Kalil; Marianna Andrande; Fabio Villas Boas; Jadelson Andrade; Ana Thereza Rocha; Robert A Harrington; Antonio C Lopes; David A Garcia Journal: J Thromb Thrombolysis Date: 2012-07 Impact factor: 2.300
Authors: V Wenzel; S G Russo; H R Arntz; J Bahr; M A Baubin; B W Böttiger; B Dirks; U Kreimeier; M Fries; C Eich Journal: Anaesthesist Date: 2010-12 Impact factor: 1.041
Authors: Renato D Lopes; Richard C Becker; John H Alexander; Paul W Armstrong; Robert M Califf; Mark Y Chan; Mark Crowther; Christopher B Granger; Robert A Harrington; Elaine M Hylek; Stefan K James; E Marc Jolicoeur; Kenneth W Mahaffey; L Kristin Newby; Eric D Peterson; Karen S Pieper; Frans Van de Werf; Lars Wallentin; Harvey D White; Antonio C Carvalho; Roberto R Giraldez; Helio P Guimaraes; Helena B Nader; Renato A K Kalil; Joyce M A Bizzachi; Antonio C Lopes; David A Garcia Journal: J Thromb Thrombolysis Date: 2011-08 Impact factor: 2.300