Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes - Phase Z of the A to Z trial
Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes - Phase Z of the A to Z trial
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DOI：
10.1001/jama.292.11.1307
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发表时间：
2004-09-15
影响因子：
120.7
通讯作者：
Braunwald, E
中科院分区：
文献类型：
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作者：
de Lemos, JA;Blazing, MA;Braunwald, E
背景有限的数据可用于评估急性冠状动脉综合征（ACS）事件后他汀类药物治疗的时间和强度如何影响临床outcome.Objective比较ACS患者早期开始强化他汀类药物治疗方案与延迟开始强度较低的治疗方案。一项双盲试验，ACS患者接受辛伐他汀40 mg/d治疗1个月，随后接受80 mg/d治疗（n=2265），与ACS患者接受安慰剂治疗4个月，随后接受辛伐他汀20 mg/d治疗（n=2232）相比，研究对象为1999年12月29日至2003年1月6日期间入组A-Z试验Z期的患者。主要结果测量主要终点为心血管死亡、非致死性心肌梗死、ACS再入院和卒中的复合终点。结果安慰剂+辛伐他汀组患者中位低密度脂蛋白胆固醇水平在服用安慰剂1个月时为122 mg/dL（3.16 mmol/L），服用辛伐他汀20 mg/d 8个月时为77 mg/dL（1.99 mmol/L）。在仅使用辛伐他汀组的患者中，服用40 mg/d辛伐他汀时，1个月时达到的中位LDL胆固醇水平为68 mg/dL（1.76 mmol/L），服用80 mg/d辛伐他汀时，8个月时达到63 mg/dL（1.63 mmol/L）。安慰剂+辛伐他汀组共有343例（16.7%）患者出现主要终点，而辛伐他汀单药组（40 mg/80 mg）有309例（14.4%）患者出现主要终点（风险比[HR]，0.89; 95%置信区间[CI] 0.76-1.04; P= 0.14）。两组分别有109例（5.4%）和83例（4.1%）患者发生心血管死亡（HR，0.75; 95% CI，0.57-1.00; P= 0.05），但在主要终点的其他个体组分中未观察到差异。在最初4个月内，两组之间的主要终点无明显差异（HR，1.01; 95%CI，0.83-1.25; P= 0.89），但从4个月至研究结束，辛伐他汀组的主要终点显著降低（HR，0.75; 95%CI，0.60-0.95; P= 0.02）。9例（0.4%）接受辛伐他汀80 mg/d的患者发生肌病（肌酸激酶>10倍正常值上限并伴有肌肉症状），接受低剂量辛伐他汀的患者无肌病发生，接受安慰剂的患者1例肌病发生（P= 0.02）。然而，在ACS患者中，早期开始积极的辛伐他汀治疗方案导致了减少主要心血管事件的有利趋势。
Context Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome.Objective To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS.Design, Setting, and Participants International, randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n=2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n=2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003.Main Outcome Measure The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, readmission for ACS, and stroke. Follow-up was for at least 6 months and up to 24 months.Results Among the patients in the placebo plus simvastatin group, the median low-density lipoprotein (LDL) cholesterol level achieved while taking placebo was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%) in the placebo plus simvastatin group experienced the primary end point compared with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95% confidence interval [CI] 0.76-1.04; P=.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in the 2 groups (HR, 0.75; 95% CI, 0.57-1.00; P=.05) but no differences were observed in other individual components of the primary end point. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95% CI, 0.83-1.25; P=.89), but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group (HR, 0.75; 95% CI, 0.60-0.95; P=.02). Myopathy (creatine kinase >10 times the upper limit of normal associated with muscle symptoms) occurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving lower doses of simvastatin, and in 1 patient receiving placebo (P=.02).Conclusions The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive simvastatin regimen resulted in a favorable trend toward reduction of major cardiovascular events.