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Beta-Blockers Increase Mortality in Hypertensive Patients


NEW YORK - Perioperative beta-blocker use in patients with hypertension is associated with increased cardiovascular complications and mortality after noncardiac surgery, researchers from Denmark report.

"The consistency of the findings of increased risks associated with beta-blockers across numerous subgroups was an important finding," Dr. Mads Emil Jorgensen from Gentofte Hospital in Hellerup said by email. "It supports our concern that in a low-risk population, beta-blocker-associated risks may outweigh the advantages of the treatment, in a wide range of low-risk patients."

Several studies have shown that perioperative beta-blocker use may benefit patients at high cardiac risk, but may increase mortality in others. Guidelines from the United States and Europe support continuing beta-blocker use perioperatively in patients already using being treated with them, but literature support for these recommendations is sparse.

Dr. Jorgensen's team used data from Statistics Denmark to investigate whether perioperative beta-blocker use is associated with an increased risk of major adverse cardiovascular events (MACEs) and all-cause mortality in the 30 days after noncardiac surgery in hypertensive patients free of cardiac, renal, and liver disease.

Among 14,644 patients treated with beta-blockers and 40,676 patients treated with other antihypertensives, the incidence of 30-day MACEs was significantly higher among those taking beta-blockers than among those taking other antihypertensives (1.32% vs. 0.84%, p<0.001).

Thirty-day all-cause mortality was also significantly higher in the beta-blocker group than in the other antihypertensives group (1.93% vs. 1.32%, p<0.001), the researchers report in JAMA Internal Medicine, online Oct. 5.

With the exception of combinations that included beta-blockers and two other antihypertensive drugs, all regimens that included a beta-blocker were associated with significantly increased risks of MACE and all-cause mortality, compared with regimens of renin-angiotensin system inhibitors and thiazides.

Results were comparable in subgroup analyses of diabetics versus nondiabetics and patients with low risk versus elevated risk.

The elevated risks were especially notable among patients at least 70 years old (number needed to harm, NNH, 140), men (NNH, 142), and patients undergoing acute surgery (NNH, 97).

"This study, among others, presents the case that the beneficial effects of beta-blockers might be subgroup dependent and that beta-blockers may not be the safe haven that previous perioperative guidelines have suggested," Dr. Jorgensen concluded. "More studies are needed to further the understanding of patient subgroups at risk, preferably in the setting of a randomized trial."

"The use of beta-blockers in 1 out of 4 patients with uncomplicated hypertension was higher than expected, as beta-blockers are no longer first-line drugs for treating hypertension," Dr. Jorgensen noted. "The high prevalence of beta-blocker use in this patient group underlines the clinical importance of these findings."

"Although we cannot conclude on whether the therapy should be changed prior to surgery, clinicians might want to pay special attention to these otherwise low-risk patients in the perioperative setting," he said.

"It is important to keep in mind that our population consisted of hypertensive patients without cardiac, renal or liver disease; thus not all patients with hypertension receiving a beta-blocker are expected to be at increased risk," Dr. Jorgensen cautioned. "Several conditions may necessitate and fully justify the use of beta-blockers, such as congestive heart failure or recent myocardial infarction, as demonstrated in a previous study from our research group."

Dr. Mark L. Friedell from the University of Missouri Kansas City School of Medicine in Kansas City coauthored one of the earlier reports that called into question the safety of perioperative beta-blocker use in low-risk patients. He said by email, "I was surprised at the higher mortality of patients with no cardiac risk factors. But, when taking the POISE trial into consideration, it makes sense that patients with no risk factors might be the ones most harmed by hypotension/stroke since there was no counter balance of cardiac protection such as that given to the patients with 3-4 cardiac risk factors."

His conclusion: "Patients with no or 1-2 cardiac risk factors do not need to be started on a beta-blocker perioperatively to try to mitigate cardiac risk."

"I think patients with perioperative hypertension and tachycardia could probably still be treated with short-acting beta-blockers," Dr. Friedell said. "If starting a beta-blocker in preparation for surgery (3-4 cardiac risk factors), do it at least a week in advance."

Dr. Elisabetta Patorno from Harvard Medical School in Boston recently coauthored a report of patterns of beta-blocker initiation in patients undergoing noncardiac surgery.

"These findings are just one piece of information and it is important not to overreact to only one study," she cautioned in an email. "These findings should be considered in addition to other available research, recommendations from professional societies like the American Heart Association, and patient specific considerations, when deciding regarding the perioperative management of patients with hypertension."

"Doctors should also balance these findings in light of the possible problems associated with this study," Dr. Patorno said. "Beta-blockers are not typically a first-line treatment for hypertension, so it is conceivable that the study participants treated with beta-blockers may have had a longer history and greater severity of hypertension compared with the patients treated with other antihypertensive therapy (the comparison group used in this study). This suggests the groups may be inherently different, with the implication that the underlying differential severity of hypertension and not the specific treatment may be responsible for the post-surgical increased risk of cardiovascular events and mortality observed among patients treated with beta-blocker therapy."

"Finally," she said, "as this study focuses on chronic antihypertensive users only, the question of whether there is real benefit or harm associated with initiating beta-blocker therapy prior to surgery remains unanswered."

Dr. Hermann Blessberger from Johannes Kepler University Linz School of Medicine, Linz, Austria, who has coauthored several papers regarding perioperative beta-blocker use, offered similar comments.

"We learned from our meta-analysis that dosage of beta-blockers (heart rate titrated), time point of start of beta-blockers before surgery (at least 2 weeks prior to surgery to allow the circulatory system to accommodate) as well as type of beta-blocker (issue with metoprolol metabolism - blood level may be heavily increased in poor metabolizers) are crucial," he said. "Except for the type of beta-blocker (mainly metoprolol and atenolol) this information could not be provided in this article as we can read in the discussion section but may be important."

"If a patient suffers from arterial hypertension, do not use a beta-blocker for initial treatment unless a beta-blocker seems desirable for another condition (rhythm disturbances, coronary heart disease, hyperthyroidism, etc.)," he advised.

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