Cardiovascular disease outcomes during 6.8 years of hormone therapy - Heart and Estrogen/progestin Replacement Study follow-up (HERS II)
Cardiovascular disease outcomes during 6.8 years of hormone therapy - Heart and Estrogen/progestin Replacement Study follow-up (HERS II)
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DOI：
10.1001/jama.288.1.49
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发表时间：
2002-07-03
影响因子：
120.7
通讯作者：
Wenger, N
中科院分区：
文献类型：
--
作者：
Grady, D;Herrington, D;Wenger, N
心脏和雌激素/黄体酮替代研究（HERS）发现绝经后冠心病妇女冠心病（CHD）事件的总体风险没有降低。然而，在激素组中，研究结果确实表明第一年发生冠心病事件的风险较高，第3至5年的风险降低。目的通过额外的随访，确定在HERS后期观察到的风险降低是否持续，并导致冠心病事件的总体风险降低。随机、盲法、安慰剂对照试验，持续4.1年（HERS），随后的非盲法随访2.7年（HERS II），在美国20个临床中心的门诊和社区环境中进行。参与HERS研究的2763名绝经后冠心病妇女，平均年龄67岁；2321名妇女（93%的幸存者）同意在HERS II中进行随访。在HERS期间，参与者被随机分配接受0.625 mg/d共轭雌激素和2.5 mg醋酸甲孕酮（n=1380）或安慰剂（n=1383）；在HERS II期间，开放标签激素治疗由个人医生自行决定，激素组中至少80%的激素依从性从81%（第1年）下降到45%（第6年），安慰剂组从0%（第1年）增加到8%（第6年）。主要结局指标主要结局是非致死性心肌梗死和冠心病死亡。继发性心血管事件包括冠状动脉血运重建术、因不稳定型心绞痛或充血性心力衰竭住院、非致死性室性心律失常、猝死、中风或短暂性脑缺血发作以及外周动脉疾病。结果：与安慰剂组相比，激素组在HERS、HERS 11或总体上的原发性冠心病事件或继发性心血管事件发生率均无显著降低，HERS组冠心病事件的未调整相对危险度（RH）为0.99(95%可信区间[CI]， 0.81-1.22)；her ii, 1.00 (95% ci, 0.77-1.29)；总体为0.99（0.84-1.17）。在校正了潜在混杂因素和不同治疗组间他汀类药物的差异使用后，总体RHs相似（RH, 0.97; 95% CI, 0.82-1.14），并且在限于坚持随机治疗分配的女性的分析中（RH, 0.96; 95% CI, 0.77-1.19）。结论：激素组妇女在HERS的最后几年冠心病发生率较低，但在后续随访中并未持续。6.8年后，激素治疗并没有降低冠心病女性心血管事件的风险。绝经后激素治疗不应用于降低冠心病患者发生冠心病的风险。
Context The Heart and Estrogen/progestin Replacement Study (HERS) found no overall reduction in risk of coronary heart disease (CHD) events among postmenopausal women with CHD. However, in the hormone group, findings did suggest a higher risk of CHD events during the first year, and a decreased risk during years 3 to 5.Objective To determine if the risk reduction observed in the later years of HERS persisted and resulted in an overall reduced risk of CHD events with additional years of follow-up.Design and Setting Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent unblinded follow-up for 2.7 years (HERS II) conducted at outpatient and community settings at 20 US clinical centers.Participants A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II.Intervention Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate (n=1380), or placebo (n=1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II, The proportions with at least 80% adherence to hormones declined from 81 % (year 1) to 45% (year 6) in the hormone group, and increased from 0% (year 1) to 8% (year 6) in the placebo group.Main Outcome Measures The primary outcome was nonfatal myocardial infarction and CHD death. Secondary cardiovascular events were coronary revascularization, hospitalization for unstable angina or congestive heart failure, nonfatal ventricular arrhythmia, sudden death, stroke or transient ischemic attack, and peripheral arterial disease.Results There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS, HERS 11, or overall, The unadjusted relative hazard (RH) for CHD events in HERS was 0.99 (95% confidence interval [CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH, 0.97; 95 % CI, 0.82-1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH, 0.96; 95% CI, 0.77-1.19).Conclusions Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.