β受体阻断剂：COPD用得太少，ACS用得太早

近期令人意外的证据提示，β受体阻断剂在慢性阻塞性肺病(COPD)的治疗中可能使用不足，而在急性心肌梗死的早期治疗中则存在使用过度的情况。

心血管疾病与COPD经由吸烟而形成了错综复杂的关系，然而对COPD患者使用β受体阻断剂却与传统观念相悖。多数医生都会避免这样做，哪怕患者合并心血管疾病，原因是担心β受体阻断剂诱发支气管痉挛和抵消β受体激动剂吸入治疗的支气管扩张益处。

不过丹佛退伍军人事务部医疗中心的Mel L. Anderson博士在科罗拉多大学主办的内科学会议上指出，来自苏格兰回顾性队列研究的数据强烈提示，上述担心是不必要的。

NHS Tayside呼吸疾病信息系统(TARDIS)在11年前建立，旨在帮助苏格兰初级保健医生和呼吸科医生更好地治疗COPD患者。不久前，Tayside的研究人员报告了对5,977例50岁以上COPD患者平均随访4.4年的结果。受试者中有819人使用β受体阻断剂，其中近90%为相对具有心脏选择性的药物，如比索洛尔或阿替洛尔。

在一项倾向性匹配评分分析中，使用β受体阻断剂加多种呼吸系统药物的患者，在随访期间发生全因死亡的风险降低22%，因COPD而住院的风险降低50%。不论有无心血管疾病，与β受体阻断剂治疗相关的上述生存收益均存在，且收益程度相似(BMJ 2011;342:d2549])。“尽管这是一项观察性研究，可能存在选择偏倚，但它仍能使我们更放心地向COPD患者提供β受体阻断剂，当然前提是他们未患哮喘。”

他还强调了β受体阻断剂应用中存在的另一个急迫问题：广泛用于有≥1个心源性休克危险因素的心肌梗死(MI)患者的早期治疗。

研究者利用美国心脏病学会(ACC)登记库——ACTION Registry-GWTG，分析了291家美国医院中34,661例ST段抬高性MI(STEMI)和非ST段抬高性MI(non-STEMI)患者在发生MI后24 h内接受β受体阻断剂治疗的结局。这一登记库是ACC全国心血管数据登记库的一部分。

ACC/美国心脏协会(AHA)关于不稳定型心绞痛/non-STEMI(J. Am. Coll. Cardiol. 2007;50:e1-e157)和STEMI(J. Am. Coll. Cardiol. 2008;51:210-47)的指南，建议对于有心源性休克危险因素的患者在最初24 h内谨慎使用β受体阻断剂。然而在ACTION Registry-GWTG研究中，早期接受β受体阻断剂治疗的STEMI 患者45%有至少1项心源性休克危险因素，这一比例在non-STEMI患者中更是高达63%。

不仅如此，ACTION登记数据表明，有心源性休克危险因素的患者早期接受β受体阻断剂治疗与结局明显恶化相关。例如，无休克危险因素的β受体阻断剂使用者，发生院内心源性休克或死亡的复合几率为1.3%，而有1项休克危险因素的使用者的复合几率增至4.8%，有2项危险因素者高达8.1%(Am. Heart J. 2011;161:864-70)。

根据COMMIT(氯吡格雷与美托洛尔在心肌梗死中的应用试验)研究(Lancet 2005;366:1,622-32)，心源性休克的危险因素包括年龄＞70岁、收缩压＜120 mmHg、心率超过110 bpm，以及STEMI患者出现症状达到或超过12 h。“相当多的患者存在心源性休克危险因素，对于这类患者，我们要么不用β受体阻断剂，要么必须非常谨慎地使用这类药物。”

有与会者询问，假如拒绝对有心源性休克危险因素的急性冠脉综合征患者使用β受体阻断剂，医生们该如何依从联合委员会的要求和达到Medicare核心绩效指标呢？Anderson博士答复称，关键在于避免对这类患者“早期”使用β受体阻断剂。一旦度过了前24 h，且患者的病情趋于平稳、心脏灌注情况好转，使用β受体阻断剂就是合理的了。

Anderson博士报告称无相关利益冲突。

爱思唯尔版权所有  未经授权请勿转载

By: BRUCE JANCIN, Cardiology News Digital Network

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.