不伴隐匿性心肌缺血的心绞痛也预示稳定性冠心病有麻烦

据欧洲心脏病学会（ESC）年会上公布的CLARIFY注册研究的分析结果，在大量病情稳定的患冠心病的门诊患者中，60%的心肌梗死（MI）或心血管死亡发生于日常生活中无心绞痛症状且无隐匿性心肌缺血证据的患者，这凸显了加强二级预防措施的必要性，即使对于无临床症状的患者亦如此。

患有心绞痛的稳定性冠心病（CAD）患者发生这些不良事件的风险要明显高于那些未患心绞痛和隐匿性心肌缺血的患者，而在心绞痛合并隐匿性心肌缺血的患者中风险甚至更高。但对于存在隐匿性缺血而无心绞痛的患者，其不良临床结局的风险与未患这两种病的患者没有明显差异。

该研究是由巴黎大学心脏病学教授Phillipe G. Steg医生等人进行的一项前瞻性注册研究，他们在2009~2010年间从45个国家招募了32,396例稳定性冠心病患者，随访时间为2年。纳入标准包括：基线时有MI病史、胸痛并有心肌缺血的证据；冠状动脉造影显示冠心病征象；既往接受过经皮冠状动脉介入治疗（PCI）或冠脉搭桥（CABG）手术。在这项分析中，Steg医生着重研究了20,402例在被招募前1年内接受过无创心肌缺血检查但因为检查结果未进行血运重建的CLARIFY参与者。他将这些患者分为四类：65%基线时既无心绞痛亦无心肌缺血，9%有心绞痛但无心肌缺血，15%有心肌缺血但无心绞痛，11%同时有心绞痛和心肌缺血。

在对同时患有心绞痛和心肌缺血的患者进行的2年随访期间，主要复合终点（心血管死亡或非致死性MI）的绝对风险不到4%。研究者认为这一低发生率与当前患者能够接受到较好的治疗有关。尽管这不是一项全球性的注册研究，但患者得到的治疗非常好，抗血小板药物、降脂疗法、ACE抑制剂和β-受体阻断药的使用率比较高。在一项针对人口学特征、吸烟状况、血脂障碍和糖尿病调整的多元分析中，患有心绞痛但无隐匿性心肌缺血的患者心血管死亡或非致死性MI的风险比既未患心绞痛也未患心肌缺血的患者高46%，具有显著的统计学差异；同时患有心绞痛和心肌缺血的患者的风险则比对照组高出76%。对于包含心血管死亡、MI、卒中或血运重建在内的次要复合终点，仅患有心绞痛组的风险相对于未患心绞痛或心肌缺血的患者上升了38%，心绞痛+心肌缺血组的风险上升了58%。值得关注的是，大出血与存在心肌缺血、心绞痛或二者同时存在没有关联。

CLARIFY注册研究由施维雅公司资助。Steg医生收到该公司提供的研究资金并担任该公司顾问，他同时为十几家其他制药公司或医疗器械公司提供了咨询服务。

爱思唯尔版权所有  未经授权请勿转载

By: BRUCE JANCIN, Cardiology News Digital Network

AMSTERDAM – Sixty percent of all myocardial infarctions and cardiovascular deaths in a large population of stable outpatients with coronary artery disease occurred in patients with neither anginal symptoms in daily life nor evidence of silent myocardial ischemia.

"This emphasizes the need to enforce secondary prevention measures, even in stable asymptomatic patients, Dr. Phillipe G. Steg observed at the annual congress of the European Society of Cardiology.

The risk of these adverse events was significantly greater in patients with stable coronary artery disease (CAD) who had angina than in those with neither angina nor silent myocardial ischemia, and higher still in those with both angina and silent ischemia. But in patients with silent ischemia and no angina, the risk of adverse clinical outcomes wasn’t significantly different than in patients with neither angina nor ischemia, added Dr. Steg, professor of cardiology at the University of Paris.

He presented an analysis from the CLARIFY registry, a prospective registry including 32,396 patients with stable CAD enrolled during 2009-2010 in 45 countries and followed up for 2 years. Participants had to have a baseline history of MI, chest pain with evidence of myocardial ischemia, evidence of CAD on coronary angiography, or prior PCI or CABG surgery.

For this analysis, Dr. Steg focused on the 20,402 CLARIFY participants who underwent noninvasive testing for myocardial ischemia within 1 year prior to enrollment and didn’t undergo revascularization as a result of the findings. These patients fell into four categories: 65% had neither angina nor myocardial ischemia at baseline, 9% had angina without ischemia, 15% had ischemia and no angina, and 11% had both angina and ischemia.

The absolute risk of the primary composite endpoint – cardiovascular death or nonfatal MI – was just under 4% in 2 years of follow-up in the patients with both angina and ischemia.

"I think that low rate corresponds to the modern environment of a well-treated patient population. Even though this was a global registry, patients were remarkably well treated, with a high rate of use of antiplatelet agents, lipid-lowering therapies, ACE inhibitors, and beta-blockers. I think it’s striking that two-thirds of the population had neither angina nor ischemia," he added.

In a multivariate analysis adjusted for demographics, smoking status, dyslipidemia, and diabetes, patients with angina but not silent ischemia had a statistically significant 46% greater risk of cardiovascular death or nonfatal MI than did those with neither angina nor ischemia. Patients with both angina and ischemia had a 76% greater risk than did the comparison group.

For the secondary composite endpoint consisting of cardiovascular death, MI, stroke, or revascularization, the angina-only group was at 38% increased risk and the angina-plus-ischemia group had a 58% greater risk than did patients with neither angina nor ischemia.

Importantly, major bleeding was not linked to the presence of ischemia, angina, or both.

The CLARIFY registry was supported by Servier. Dr. Steg has received research funding from and served as a consultant to the company. He has also consulted for a dozen other pharmaceutical or medical device companies.