Mahaffey Kenneth W, Cohen Marc, Garg Jyotsna, Antman Elliott, Kleiman Neal S, Goodman Shaun G, Berdan Lisa G, Reist Craig J, Langer Anatoly, White Harvey D, Aylward Philip E, Col Jacques J, Ferguson James J, Califf Robert M
Duke Clinical Research Institute, Durham, NC 27715, USA.
JAMA. 2005 Nov 23;294(20):2594-600. doi: 10.1001/jama.294.20.2594.
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.
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.
Six-month outcomes were death, nonfatal MI, revascularization procedures, stroke, and site-investigator-reported need for rehospitalization; 1-year outcome was all-cause death.
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).
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.
SYNERGY试验比较了依诺肝素与普通肝素在高危急性冠脉综合征（ACS）患者中的应用，结果显示，在30天时依诺肝素在降低死亡或非致命性心肌梗死（MI）方面不劣于普通肝素。
通过6个月和1年的随访评估该患者队列的持续风险。
设计、地点和患者：总体而言，2001年8月至2003年12月期间，12个国家的487家医院对9978例患者进行了随机分组。对患者进行了6个月和1年的随访。
6个月的结局指标为死亡、非致命性MI、血运重建术、卒中以及研究点调查员报告的再次住院需求；1年的结局指标为全因死亡。
9978例患者中，分别有9957例（99.8%）和9608例（96.3%）获得了6个月和1年的随访数据；541例患者（5.4%）在6个月时死亡，739例（7.4%）在1年时死亡。6个月时，接受依诺肝素治疗的872例患者（17.6%）发生死亡或非致命性MI，接受普通肝素治疗的884例患者（17.8%）发生死亡或非致命性MI（风险比[HR]，0.98；95%置信区间[CI]，0.89 - 1.07；P = 0.65）。在接受持续治疗的患者亚组中，即住院期间仅接受依诺肝素或普通肝素治疗的患者（n = 6138），依诺肝素在180天时仍能降低死亡或非致命性MI的发生率（HR，0.85；95% CI，0.75 - 0.95；P = 0.006）。180天内，接受依诺肝素治疗的858例患者（17.9%）再次住院，接受普通肝素治疗的911例患者（19.0%）再次住院（HR，0.94；95% CI，0.85 - 1.03；P = 0.17）。两个治疗组的1年全因死亡率相似（依诺肝素组为380/4974 [7.6%]，普通肝素组为359/4948 [7.3%]；HR，1.06；95% CI，0.92 - 1.22；P = 0.44）。接受持续治疗的患者1年死亡率也相似（依诺肝素组为251/3386 [7.4%]，普通肝素组为213/2720 [7.8%]；HR，0.95；95% CI，0.79 - 1.14；P = 0.55）。
在SYNERGY试验中，通过长期随访发现患者仍持续经历不良心脏事件。在总体试验和持续治疗组中，依诺肝素与普通肝素相比，6个月时对死亡或MI的影响与30天时观察到的相似。两组的1年死亡率也相似。尽管进行了积极治疗，但高危ACS患者仍易发生持续性心脏事件。临床试验注册号：NCT00043784。
