围手术期使用β受体阻断剂可降低死亡率

据4月24日《美国医学会杂志》(JAMA)上发表的一篇文章，对于接受大型非心脏手术的心脏病高危患者而言，在围手术期早期使用β受体阻断剂与30天全因死亡率及心脏并发症发生率显著降低相关，并且在心脏病最高危患者中相关性最强。

Martin London医生

β受体阻断剂在这类患者中的应用目前仍存在争议，而且鉴于安全性方面的担忧，围手术期β受体阻断剂的应用正在减少。为了探讨高危患者使用这类药物的利弊，旧金山市美国退伍军人事务部(VA)医疗中心麻醉与围手术期医疗部的Martin J. London医生及其合作者开展了一项回顾性队列研究，对VA外科手术质量提高计划数据库、VA药房数据库及VA行政数据库中的数据进行分析，具体分析了136,745例于2005~2010年间接受血管、普外、神经、整形、胸部、泌尿或耳鼻喉手术的患者，共涉及104家VA医疗中心。其中40.3%的受试者在手术当天或次日服用了β受体阻断剂，33.2%在手术7天内接受了β受体阻断剂门诊处方。

在5年研究期间，β受体阻断剂的应用呈现小幅但具有统计学意义的下降，从第1年的43.5%降至最后1年的36.2%。既往研究也曾报道过相近的趋势。研究者表示，这可能与POISE试验显示的治疗组患者卒中和死亡例数增加有关，该结果导致这段时期内的治疗指南更加保守。

在主要结局分析中，研究者们进行了1:1的倾向性匹配，查到37,805对匹配的暴露和未暴露患者。主要结局指标为30天全因死亡率，使用β受体阻断剂治疗的患者与未使用者相比，该指标显著降低(相对风险为0.73)，需治疗的患者数为241例(JAMA 2013;309:1704-13)。

研究者根据修订心脏危险指数(CRI)评分对受试者进行了分类。CRI包括6个变量：高危手术、心脑血管病、缺血性心脏病、心力衰竭、糖尿病及肾功能不全。具备至少2项CRI危险因素的患者(即心脏病最高危患者)从围手术期β受体阻断剂治疗中获得的死亡率收益最大，相对风险为0.63。根据手术类型将数据细分时发现，β受体阻断剂使用者的死亡率仍较未使用者显著降低，只有血管手术例外，而既往研究显示血管手术患者使用β受体阻断剂的获益与其他类型手术患者相当。

本研究的次要结局指标为30天Q波心肌梗死或非致死性心脏骤停复合发生率，这两种病症属于罕见并发症，但却是后续死亡率的高预测指标。结果与主要结局相似，服用β受体阻断剂的患者的心脏并发症发生率显著低于未服用者，相对风险为0.67，需治疗的例数为339。

将患者按照住院前是否一直在服用β受体阻断剂进行分类及将患者按照短期或长期使用β受体阻断剂进行分类后，在敏感性分析中上述研究结果仍具有鲁棒性。

该研究证实了既往的研究结果，即在手术30天内停用β受体阻断剂与死亡率增加相关。在本研究中，若在围手术期停用β受体阻断剂，死亡风险会增加约1倍。在事后分析中，研究者未能证实围手术期β受体阻断剂应用与术后卒中风险有显著相关性。接受β受体阻断剂治疗的患者与未使用者在卒中发生率上无显著差异。

本研究由麻醉患者安全基金会资助。London医生无经济利益冲突披露。一位合作者报告与罗氏、Resverlogie、Anthera及赛诺菲有关联。

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By: MARY ANN MOON, Internal Medicine News Digital Network

For patients at elevated cardiac risk who are undergoing major noncardiac surgery, early perioperative use of beta-blockers is associated with significantly lower 30-day all-cause mortality and cardiac morbidity, according to a report in the April 24 issue of JAMA.

In a retrospective cohort study, this association was strongest in the patients at highest cardiac risk – those with two or more factors on the six-item Cardiac Risk Index, said Dr. Martin J. London of the department of anesthesia and perioperative care, U.S. Department of Veterans Affairs Medical Center, San Francisco, and his associates.

Beta-blocker use in this setting remains controversial, and the use of perioperative beta-blockers has been declining, because of safety concerns. To examine whether high-risk patients are helped or harmed by the treatment, Dr. London and his colleagues analyzed data from the VA Surgical Quality Improvement Program database, a VA pharmacy database, and a VA administrative database.

They assessed the records of 136,745 patients who had vascular, general, neurologic, orthopedic, thoracic, urologic, or otolaryngologic surgery at 104 VA medical centers in 2005-2010.

A total of 40.3% of these subjects had received beta-blockers on the day of or the day after surgery, and 33.2% were given outpatient prescriptions for beta-blockers within 7 days of surgery.

There was a modest but significant decline in beta-blocker use during the 5-year study period, from 43.5% in the first year to 36.2% in the last. A similar national trend has been reported in previous studies. "This may be related to the findings of the POISE trial of increased stroke and death in treated patients, leading to more conservative guideline recommendations within this period," the investigators said.

They performed 1:1 propensity matching and identified 37,805 matched pairs of exposed and nonexposed patients for the primary outcome analysis. The primary outcome measure – all-cause mortality at 30 days – was significantly lower (relative risk 0.73) among patients who used beta-blockers than among those who did not, with a number needed to treat of 241 (JAMA 2013;309:1704-13).

The study subjects were categorized according to their scores on the revised Cardiac Risk Index, which includes six variables: high-risk surgery, cerebrovascular disease, ischemic heart disease, heart failure, diabetes, and renal insufficiency. Patients who had two or more of these CRI risk factors showed the greatest mortality benefit from perioperative beta-blocker therapy, with an relative risk of 0.63.

When the data were broken down by type of surgery, mortality remained significantly lower in beta-blocker users, compared with nonusers for every category except vascular surgery. In previous studies, beta-blockers have shown equivocal benefit in this same subgroup of surgery patients, Dr. London and his associates noted.

The secondary outcome measure of the study was a composite of Q-wave myocardial infarction or nonfatal cardiac arrest at 30 days. These may be rare complications but they are highly predictive of subsequent mortality, the researchers said.

Again, patients who took beta-blockers showed significantly less cardiac morbidity than those who did not, with a relative risk of 0.67 and a number needed to treat of 339.

The study results remained robust in a sensitivity analysis that categorized patients according to whether they had been taking beta-blockers before hospitalization, as well as in a sensitivity analysis that categorized patients as either acute or chronic users of beta-blockers.

This study confirmed the previous finding that withdrawal of beta-blockers within 30 days of surgery is associated with increased mortality. In this study, the risk of death was approximately doubled if beta-blockers were withdrawn perioperatively.

In a post hoc analysis, "we were unable to demonstrate significant associations of perioperative beta-blockade with the risk of postoperative stroke." There was no significant difference in stroke rates between patients who received beta-blockers and those who did not, Dr. London and his colleagues said.

This study was supported by a grant from the Anesthesia Patient Safety Foundation. Dr. London reported no financial conflicts of interest. An associate reported ties to Roche, Resverlogie, Anthera, and Sanofi.