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.
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The researchers found that initiation of a course of beta-blockers as per guideline recommendations before surgery was linked to a 27% increase in mortality.
"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.