JAMA：用抗抑郁症药物治疗可降低精神刺激诱发的心肌缺血发生率

据发表在5月22/29日刊《美国医学会杂志》上的一则研究披露，在罹患稳定型冠心病及精神压力诱发的心肌缺血（MSIMI）患者中，与安慰剂相比，用抗抑郁药艾司西酞普兰治疗6周可降低MSIMI发生率。

根据文章的背景资料：“有一系列强有力的证据已经确认情绪压力是冠心病（CHD）及其它心血管事件的一个可能的触发因子” 。“在过去的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很好的研究。在实验室的环境中，MSIMI出现在高达70%的临床上稳定的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。 最近的证据提示，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。

北卡罗来纳州达勒姆的杜克大学医学中心的Wei Jiang, M.D.及其同事开展了一项研究，旨在调查选择性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）。 这项随机试验包括了患有临床稳定性冠心病及得到实验室诊断的精神压力诱发的心肌缺血（MSIMI）患者。这些患者是从2007年7月至2011年8月在一个三级医疗中心被招募到本研究中的。 符合条件的参与者按1:1的比例被随机性地指派接受艾司西酞普兰或安慰剂达6周时间。 每一组中共有56名患者完成了终点评估。精神压力诱发的心肌缺血（MSIMI）的发生是在进行3个精神压力因素作业中的1或多个时，通过多种检测对其进行定义的，这些精神压力因素作业有：心算、镜描以及带有愤怒回忆的公开演说。

研究人员发现，在6个星期结束时，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个精神刺激因子作业时没有发生精神压力诱发的心肌缺血（MSIMI）。分析显示，艾司西酞普兰组与安慰剂组相比有着显着较高（2.6倍）的MSIMI阴性率。 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，而组间的心率差异是显着的。

此外，6周的艾司西酞普兰干预与心里运作的某些检测上的较大改善有关，其中包括在精神刺激时的状态性焦虑和正向情感。

在接受艾司西酞普兰vs. 接受安慰剂的参与者中，他们在第6周时的运动能力没有显着的改变。

文章的作者得出结论：“综上所述，为期6周的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）管理的叠加看来能显着地改善MSIMI的发生。这些结果支持并扩展了先前的发现，这些发现提示改变中枢和外周5-羟色胺能神经功能可改善冠心病（CHD）症状并可能对人们理解负面情感影响心血管事件预后的通路具有意义。”（生物谷Bioon.com）

生物谷推荐英文摘要：

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.