JAMA：艾司西酞普兰可显著减少精神刺激诱发的心肌缺血发生率

发表于《美国医学会杂志》5月22/29日刊在线版的一项研究显示，对于稳定型冠心病及精神紧张诱发的心肌缺血（MSIMI）患者，使用抗抑郁药艾司西酞普兰治疗6周与安慰剂相比，可降低MSIMI发生率。
“已存在相当数量的有力证据证明情绪压力是冠心病（CHD）及其它心血管事件的潜在触发因子，”文章的背景信息写道。“在最近的30年中，对情绪苦恼与心肌缺血性活动[心肌血流量不足，常常会引起胸痛]之间的关系已经在实验室中得到了充分研究。在实验室情境中，MSIMI出现在高达70%的临床病情稳定的CHD病人中，且它与死亡和心血管事件风险的增加有关。”几乎没有研究检查过能有效改变MSIMI的疗法。 近来的证据提示，选择性5-羟色胺再摄取抑制剂（SSRIs）可能会减少精神压力诱发的血流动力学反应、代谢风险因子及血小板的活性。
北卡罗来纳州Durham市杜克大学医学中心的Wei Jiang博士及其同事开展了一项研究，旨在明确选择性5-羟色胺再摄取抑制剂（SSRIs）治疗是否能改善精神压力诱发的心肌缺血（MSIMI）。 这项随机试验纳入了患有临床稳定性冠心病及实验室诊断为精神压力诱发的心肌缺血（MSIMI）患者。这些受试者来自于从2007年7月至2011年8月在一个三级医疗中心接受治疗的患者。 符合条件的受试者按1:1的比例进行随机分组分别接受艾司西酞普兰或安慰剂治疗6周时间。 每一组中有56名患者完成了终点评估。精神压力诱发的心肌缺血（MSIMI）的发生被定义为在进行3项含精神压力因素的工作的1或多个时，通过多种算法对其指数进行测量，这些含精神压力因素的工作包括：心算、镜描以及带有愤怒回忆的公众讲话。
研究人员还发现，在6个星期即将结束时，与服用安慰剂的病人（17.5%）相比，有更多的服用艾司西酞普兰的病人（34.2%）在3个含精神刺激因子工作时没有发生精神压力诱发的心肌缺血（MSIMI）。分析显示，与安慰剂组相比，艾司西酞普兰组的MSIMI阴性率显著增加（2.6倍）。 此外，艾司西酞普兰组对精神刺激的血流动力学反应全部较低，而组间的收缩压和心率有显著性差异。此外，6周的艾司西酞普兰介入可很大程度上改善心理功能的某些测量值，其中包括在精神刺激时的状态性焦虑和正能量情感。在接受艾司西酞普兰vs. 接受安慰剂的受试者中，他们在第6周时的运动能力没有显著性变化。
文章的作者由此得出结论：“总之，在6周的治疗时间里患者表现出5-羟色胺能神经功能的药理学增强与最好的循证冠心病（CHD）管理的叠加，提示该方案或能显著性改善MSIMI的发生率。这些结果支持并拓展了先前的研究结果，提示对中枢和外周5-羟色胺能神经功能的改善可缓解冠心病（CHD）症状，并可能对影响负面情感影响心血管事件预后通路的理解产生影响。”

Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial.
IMPORTANCE
Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress-induced myocardial ischemia (MSIMI) have not been well studied.
OBJECTIVE
To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters.
DESIGN, SETTING, AND PARTICIPANTS
The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center.
INTERVENTIONS
Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks. MAIN OUTCOMES AND MEASURES: Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks.
RESULTS
Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 mental stressor tasks compared with patients taking placebo (17.5% [95% CI, 10.4%-24.5%]), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62 [95% CI, 1.06-6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6%-55.0%]) than in patients receiving placebo (52.5% [95% CI, 43.3%-61.8%]), but this difference was not statistically significant (adjusted odds ratio; 1.24 [95% CI, 0.60-2.58]; P = .56).
CONCLUSIONS AND RELEVANCE
Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed.