摘要
Context: Despite many therapeutic advances, mortality in patients with acute S T-segment elevation myocardial infarction(STEMI) remains high. The role of addi tional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. Objective: To evaluate the effect of fondaparinux, a facto r Xa inhibitor, when initiated early and given for up to 8 days vs usual care(pl acebo in those in whom unfractionated heparin[UFH] is not indicated[stratum 1] o r unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. Design, Setting, and Participants: Randomiz ed double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries(Septe mber 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main O utcome Measures: Composite of death or reinfarction at 30 days(primary) with sec ondary assessments at 9 days and at final follow-up(3 or 6 months). Results: Death or reinfarction at 30 days was significantly reduced from 677(11.2%) of 6056 patients in the control group to 585(9.7%) of 6036 patients in the fondaparin ux group(hazard ratio[HR], 0.86; 95%confidence interval[CI], 0.77-0.96; P=.008 ); absolute risk reduction, 1.5%; 95%CI, 0.4%-2.6%). These benefits were ob served at 9 days(537[8.9%] placebo vs 444[7.4%] fondaparinux; HR, 0.83; 95%CI , 0.73-0.94; P=.003), and at study end(857[14.8%] placebo vs 756[13.4%] fonda parinux; HR, 0.88; 95%CI, 0.79-0.97; P=.008). Mortality was significantly redu ced throughout the study. There was no heterogeneity of the effects of fondapari nux in the 2 strata by planned heparin use. However, there was no benefit in tho se undergoing primary percutaneous coronary intervention. In other patients in s tratum 2, fondaparinux was superior to unfractionated heparin in preventing deat h or reinfarction at 30 days(HR, 0.82; 95%CI, 0.66-1.02; P=.08) and at study e nd(HR, 0.77; 95%CI, 0.64-0.93; P=.008). Significant benefits were observed in those receiving thrombolytic therapy(HR, 0.79; P=.003) and those not receiving a ny reperfusion therapy(HR, 0.80; P=.03). There was a tendency to fewer severe bleeds(79 for placebo vs 61 for fondaparinux; P=.13), with significantly fewer car diac tamponade(48 vs 28; P=.02) with fondaparinux at 9 days. Conclusion: In pati ents with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction wit hout increasing bleeding and strokes.
Context： Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction（STEMI） remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving re the effect of fo perfusion therapy. Objective： To evaluate ndaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care （placebo in those in whom unfractionated heparin[UFH] is not indicated[stratum 1 ] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [ stratum 2 ] ） in patients with STEMI. Design, Setting, and Participants： Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries（September 2003- January 2006） From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main Outcome Measures： Composite of death or reinfarction at 30 days （primary） with secondary assessments at 9 days and at final follow-up（3 or 6 months）. Results： Death or reinfarction at 30 days was significantly reduced from 677（11.2% ） of 6056 patients in the control group to 585（9.7% ） of 6036 patients in the fondaparinux group（hazard ratio[HR], 0.86; 95% confidence interval[CI], 0.77-0.96; P= .008）; absolute risk reduction, 1.5% ; 95% CI, 0. 4% -2. 6% ） . These benefits were observed at 9 days（537 [8.9% ] placebo vs 44417.4% ] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P=.003）, and at study end（857[14. 8% ] placebo vs 756113.4% ] fondaparinux; HR, 0.88; 95% CI, 0. was significantly reduced 79 - 0.97; P =. 008）. Mortality throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention.
