CONTEXT: The SYNERGY trial comparing enoxaparin and unfractionated heparin in high-risk patients with acute coronary syndromes (ACS) showed that enoxaparin was not inferior to unfractionated heparin in reducing death or nonfatal myocardial infarction (MI) at 30 days. OBJECTIVE: To evaluate continued risk in this patient cohort through 6-month and 1-year follow-up. DESIGN, SETTING, AND PATIENTS: Overall, 9978 patients were randomized from August 2001 through December 2003 in 487 hospitals in 12 countries. Patients were followed up for 6 months and for 1 year. MAIN OUTCOME MEASURES: Six-month outcomes were death, nonfatal MI, revascularization procedures, stroke, and site-investigator-reported need for rehospitalization; 1-year outcome was all-cause death. RESULTS: Six-month and 1-year follow-up data were available for 9957 (99.8%) and 9608 (96.3%) of 9978 patients, respectively; 541 patients (5.4%) had died at 6 months and 739 (7.4%) at 1 year. Death or nonfatal MI at 6 months occurred in 872 patients receivingenoxaparin (17.6%) vs 884 receiving unfractionated heparin (17.8%) (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.89-1.07; P = .65). In the subgroup of patients receiving consistent therapy, ie, only enoxaparin or unfractionated heparin during the index hospitalization (n = 6138), a reduction in death or nonfatal MI with enoxaparin was maintained at 180 days (HR, 0.85; 95% CI, 0.75-0.95; P = .006). Rehospitalization within 180 days occurred in 858 patients receivingenoxaparin (17.9%) and 911 receiving unfractionated heparin (19.0%) (HR, 0.94; 95% CI, 0.85-1.03; P = .17). One-year all-cause death rates were similar in the 2 treatment groups (380/4974 [7.6%] for enoxaparin vs 359/4948 [7.3%] for unfractionated heparin; HR, 1.06; 95% CI, 0.92-1.22; P = .44). One-year death rates in patients receiving consistent therapy were also similar (251/3386 [7.4%] for enoxaparin vs 213/2720 [7.8%] for unfractionated heparin; HR, 0.95; 95% CI, 0.79-1.14; P = .55). CONCLUSIONS: In the SYNERGY trial, patients continued to experience adverse cardiac events through long-term follow-up. The effect of enoxaparin on death or MI compared with that of unfractionated heparin at 6 months was similar to that observed at 30 days in the overall trial and in the consistent-therapy group. One-year death rates were also similar in both groups. High-risk patients with ACS remain susceptible to continued cardiac events despite aggressive therapies.ClinicalTrials.gov Identifier: NCT00043784.
RCT Entities:
CONTEXT: The SYNERGY trial comparing enoxaparin and unfractionated heparin in high-risk patients with acute coronary syndromes (ACS) showed that enoxaparin was not inferior to unfractionated heparin in reducing death or nonfatal myocardial infarction (MI) at 30 days. OBJECTIVE: To evaluate continued risk in this patient cohort through 6-month and 1-year follow-up. DESIGN, SETTING, AND PATIENTS: Overall, 9978 patients were randomized from August 2001 through December 2003 in 487 hospitals in 12 countries. Patients were followed up for 6 months and for 1 year. MAIN OUTCOME MEASURES: Six-month outcomes were death, nonfatal MI, revascularization procedures, stroke, and site-investigator-reported need for rehospitalization; 1-year outcome was all-cause death. RESULTS: Six-month and 1-year follow-up data were available for 9957 (99.8%) and 9608 (96.3%) of 9978 patients, respectively; 541 patients (5.4%) had died at 6 months and 739 (7.4%) at 1 year. Death or nonfatal MI at 6 months occurred in 872 patients receiving enoxaparin (17.6%) vs 884 receiving unfractionated heparin (17.8%) (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.89-1.07; P = .65). In the subgroup of patients receiving consistent therapy, ie, only enoxaparin or unfractionated heparin during the index hospitalization (n = 6138), a reduction in death or nonfatal MI with enoxaparin was maintained at 180 days (HR, 0.85; 95% CI, 0.75-0.95; P = .006). Rehospitalization within 180 days occurred in 858 patients receiving enoxaparin (17.9%) and 911 receiving unfractionated heparin (19.0%) (HR, 0.94; 95% CI, 0.85-1.03; P = .17). One-year all-cause death rates were similar in the 2 treatment groups (380/4974 [7.6%] for enoxaparin vs 359/4948 [7.3%] for unfractionated heparin; HR, 1.06; 95% CI, 0.92-1.22; P = .44). One-year death rates in patients receiving consistent therapy were also similar (251/3386 [7.4%] for enoxaparin vs 213/2720 [7.8%] for unfractionated heparin; HR, 0.95; 95% CI, 0.79-1.14; P = .55). CONCLUSIONS: In the SYNERGY trial, patients continued to experience adverse cardiac events through long-term follow-up. The effect of enoxaparin on death or MI compared with that of unfractionated heparin at 6 months was similar to that observed at 30 days in the overall trial and in the consistent-therapy group. One-year death rates were also similar in both groups. High-risk patients with ACS remain susceptible to continued cardiac events despite aggressive therapies.ClinicalTrials.gov Identifier: NCT00043784.
Authors: Kenneth W Mahaffey; Qinghong Yang; Karen S Pieper; Elliott M Antman; Harvey D White; Shaun G Goodman; Marc Cohen; Neal S Kleiman; Anatoly Langer; Philip E Aylward; Jacques J Col; Craig Reist; James J Ferguson; Robert M Califf Journal: J Gen Intern Med Date: 2008-01-15 Impact factor: 5.128