指南推荐的术前β受体阻断剂用法不合理

一项meta分析显示，如果不采纳美国心脏病学会基金会(ACCF)/美国心脏协会(AHA)指南和欧洲心脏病学会(ESC)指南的建议，在非心脏手术前不使用β受体阻断剂，那么每4例术后死亡患者中就有至少1例可以幸免。

主要研究者、伦敦帝国学院国立心肺研究所的Sonia Bouri博士指出：“因此，如果能对ESC指南进行相应调整，就有望在英国每年避免多达10,000例医源性死亡。”

上述指南建议，所有接受血管或中等风险手术的患者，或者具有1种以上冠心病危险因素的患者，或者已在服用β受体阻断剂的患者，应在术前使用β受体阻断剂。

Bouri博士及其同事对9项安全性随机试验进行了meta分析，共涉及10,529例符合指南标准的患者，其中291例死亡。研究者发现，如果按照指南建议在术前启动β受体阻断剂治疗，会导致死亡率增加27%。在这些安全性试验中，术前使用β受体阻断剂可显著减少非致死性心肌梗死(RR，0.73；P=0.001)，但同时会增加卒中(RR，1.73；P=0.05)和低血压(RR，1.51；P＜0.00001)。这一结果发表在《心脏》杂志上(2013 July 31 [doi: 10.1136/heartjnl-2013-304262])。

在291例死亡中，162例死亡(3.21%)来自5,264例被随机分至β受体阻断剂组的患者，129例死亡(2.45%)来自5,265例被随机分至安慰剂组的患者。因此，按照指南建议在术前启动β受体阻断剂治疗导致全因死亡率升高了27%。研究者补充道：“那些仍然热衷于使用β受体阻断剂的人最好把精力用到更深入的随机试验中，而且应当采用细致和诚实的试验设计。”

这项meta分析排除了来自荷兰应用负荷超声心动检查评估心脏风险(DECREASE)系列试验的数据，该系列试验如今已经受到了质疑。Meta分析的结果实质上确实与DECREASE系列试验的结果大相径庭(分歧度P=0.05)。“DECREASE系列的所有试验都接受了调查，结果显示尚未遗失的数据存在严重瑕疵，因而是不安全的。例如，整个研究数据库都是捏造的。发表于1999年的DECREASE Ⅰ试验逃过了调查，原因是调查最多只回溯到10年前。”

在ESC和(ACCF)/(AHA)制定出指南后，“DECREASE系列试验数据不安全的调查结论使他们得出了‘β受体阻断剂对死亡率的影响为中性’的结论，并将关注点转向非致死性心肌梗死的降低，将其作为了替代终点”。

DECREASE系列试验是在大约2年前受到质疑的，随后接受了漫长的内部调查，其结果已发表。“然而，ESC和(ACCF)/(AHA)均未撤回其指南。”研究者总结道：“患者安全是最重要的，没有理由拖延对有关术前使用β受体阻断剂的指南的撤回工作。未来的指南应当附带一项承诺，即获得授权者可以在发现推荐意见实际上有害的情况下立即撤回指南。”

这项meta分析的作者均报告称无相关利益冲突。

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By: MARK S. LESNEY, Cardiology News Digital Network

More than 1 in 4 patients who died from all causes after noncardiac surgery may have survived if they were not treated with perioperative beta-blockers as specified by joint American College of Cardiology Foundation/American Heart Association and separate European Society of Cardiology guidelines.

These guidelines recommend perioperative beta-blockers in all patients undergoing vascular or intermediate-risk surgery with coronary artery disease, or with more than one risk factor for CAD, or with preexisting beta-blockade. These are all iatrogenic deaths, according to a meta-analysis of secure studies, which excluded data from the now discredited Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of trials.

"Refraining from this ESC [European Society of Cardiology] guideline would therefore be expected to prevent up to 10,000 iatrogenic deaths each year in the U.K.," according to Dr. Sonia Bouri and her coauthors at the National Heart and Lung Institute, Imperial College London.

The researchers analyzed nine secure randomized trials totaling 10,529 patients who met the guideline criteria, 291 of whom died. They found that initiation of a course of beta-blockers as per guideline recommendations before surgery resulted in a 27% increase in mortality.

In the secure trials, use of perioperative beta-blockers decreased nonfatal myocardial infarction significantly (RR, 0.73; P = .001), but increased stroke (RR, 1.73; P =.05) and hypotension (RR, 1.51; P less than .00001), according to the authors, who presented their data in Heart (2013 July 31 [doi: 10.1136/heartjnl-2013-304262]).

Of the 291 deaths recorded in the secure trials, 162 deaths (3.21%) occurred in 5,264 patients randomized to beta-blockers, and 129 deaths (2.45%) occurred in the 5,265 patients randomized to placebo.

Thus, the initiation of a course of beta-blockers as per guideline recommendations before surgery resulted in a 27% increase in all-cause mortality, Dr. Bouri and her coauthors stated. "Any remaining [perioperative beta-blocker] enthusiasts might best channel their energy into a further randomized trial, which should be designed carefully and honestly," they added.

The results from the DECREASE family of trials substantially contradicted the meta-analysis of the secure trials on the effect on mortality (P = .05 for divergence).

"All studies investigated in the DECREASE family for which data had not been lost were found to be insecure because of serious flaws. In one case, it was clear that the entire study database had been fabricated. DECREASE I, published in 1999, escaped investigation as the terms of the investigation only reached back 10 years," the researchers reported.

When the ESC and American College of Cardiology Foundation/American Heart Association guidelines were formulated, "the inclusion of insecure data caused them to reach the conclusion that beta-blockade had a neutral effect on mortality and allowed them to focus on the reduction of non-fatal MI as a surrogate endpoint," the authors explained.

The DECREASE family of studies was discredited almost 2 years ago and subsequently underwent lengthy internal investigation, the results of which have been public for some time, according to the authors. "Nevertheless, neither the European Society of Cardiology nor the AHA guidelines have been retracted," they said.

"Patient safety being paramount, guidelines for perioperative beta-blockers should be retracted without further delay. Future guidelines should be accompanied by a commitment from named individuals to retract them immediately if the advice given is later revealed to be harmful," the authors concluded.

The authors reported that they had no conflicts of interest.