High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial.
BACKGROUND
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.


METHODS
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.


METHODS
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.
Mahaffey
Kenneth W
KW
Duke Clinical Research Institute, Durham, NC 27715, USA. mahaf002@mc.duke.edu
Cohen
Marc
M
Garg
Jyotsna
J
Antman
Elliott
E
Kleiman
Neal S
NS
Goodman
Shaun G
SG
Berdan
Lisa G
LG
Reist
Craig J
CJ
Langer
Anatoly
A
White
Harvey D
HD
Aylward
Philip E
PE
Col
Jacques J
JJ
Ferguson
James J
JJ
Califf
Robert M
RM
D017984:Enoxaparin / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality; D009204:Myocardial Revascularization; D012306:Risk; D020521:Stroke / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006493:Heparin