Back and forth on beta-blockers

Hospitalists are weighing the risks vs. benefits of administering beta-blockers.

Hospitalists have new evidence to balance the risks and benefits of beta-blockers in certain patients. In a recent study of nearly 16,000 older nursing home residents, starting beta-blockers after an acute myocardial infarction (AMI) lowered the 90-day risk of mortality by about 25%, but significantly increased the likelihood of functional decline, especially when patients had moderate or severe cognitive impairment or severe functional dependency.

“We think this is a new discovery,” said Michael A. Steinman, MD, FACP, professor of medicine in the division of geriatrics at the University of California, San Francisco, who reported the findings in the February 2017 JAMA Internal Medicine.

Evidence and the experts are more certain about the value of beta-blockers for most patients with heart failure Image by Thinkstock
Evidence and the experts are more certain about the value of beta-blockers for most patients with heart failure. Image by Thinkstock

Beta-blockers can cause fatigue, dizziness, and a decreased sense of well-being, which might be “the straw that broke the camel's back” for frail, elderly patients, Dr. Steinman said. “This might be an example of how adverse effects that are tolerable in a relatively robust older adult can tip a vulnerable older adult ‘over the edge’ into bad outcomes.”

That means that among the many factors determining whether a patient should take beta-blockers, hospitalists should also now consider older patients' functional and cognitive status.

For AMI patients with no more than mild dementia and at least moderate functional abilities, beta-blockade seems to prevent mortality without leading to functional decline, Dr. Steinman said. But if patients do not meet those criteria, “decisions about beta-blocker use should be driven by goals of care. If patients strongly value staying alive, beta-blockers are a good choice. But if the patient values preserving function more than prolonging lifespan, it may be reasonable not to prescribe a beta-blocker.”

Questions on post-AMI use

Such findings challenge decades-old notions about the universal benefits of beta-blockers after AMI, said Jeffrey Goldberger, MD, FACP, chief of the cardiovascular division at the University of Miami in Florida. “In patients with recent MI, the major new questions are: Do all patients require treatment? What is the optimal dose? How long do patients need to be treated?” he said.

When considering whether to prescribe a beta-blocker in a patient hospitalized with cardiovascular disease, including AMI, Dr. Goldberger recommends asking, “Will it make the patient feel better? Will it improve survival? Will it prevent other cardiovascular morbidity, such as hospitalization for heart failure?”

Most patients with AMI should start a beta-blocker in the hospital, but optimal dosing remains a question, he noted. In a study of nearly 7,000 patients with acute AMI, low-dose beta-blockers improved two-year survival as effectively as the higher doses typically used in clinical trials, Dr. Goldberger reported in the September 29, 2015, Journal of the American College of Cardiology. The findings highlight the need for more research on appropriate beta-blocker dosing after AMI, he concluded.

How long to continue beta-blockers after AMI also remains uncertain. There is no clear evidence supporting beta-blockade beyond one year in patients with a history of AMI without left ventricular dysfunction, angina, or dysrhythmia, experts noted in an editorial accompanying Dr. Steinman's study. Clinicians also lack protocols on tapering therapy and solid data on the potential benefits and harms of doing so, the editorialists noted.

Accordingly, they suggested a five-step approach to deciding whether to taper medications such as beta-blockers. Clinicians and patients can list all prescriptions and the reason for each, evaluate the overall risks of drug-induced harm, consider whether each drug can be discontinued, and decide which, if any, to stop. Finally, they can begin a discontinuation regimen with careful follow-up, the editorialists advised.

Heart failure

The evidence and the experts are more certain about the value of beta-blockers for most patients with heart failure. In a study of more than 2,000 Medicare beneficiaries hospitalized with heart failure and ejection fraction below 45%, beta-blockers at discharge were associated with a 70% decrease in the risk of mortality at 30 days and a 20% decrease at four years, investigators reported in the July 2015 American Journal of Medicine.

“The evidence for long-term use of beta-blockade in patients with reduced ejection fraction, along with [angiotensin-converting enzyme] inhibitors and aldosterone antagonists, is some of the most compelling that we have in internal medicine in terms of absolute risk reduction for mortality,” said Frank Merritt, MD, a hospitalist and instructor of medicine at the University of Colorado Anschutz Medical Center in Aurora. For these patients, hospitalists play a crucial role by starting beta-blockers before discharge, he said. The American Heart Association recommends this “common-sense approach,” which helps ensure this step is not missed during follow-up visits, he added.

Dr. Merritt usually prescribes these patients beta-blockers for at least one month. But beta-blockers are not always appropriate in heart failure, he noted. Because beta-blockers reduce short-term cardiac output, hospitalists should be “extremely cautious” about starting or resuming them in patients with severely decompensated heart failure, especially those who recently received inotropes and have not yet been adequately diuresed. These cases merit input from a cardiologist, Dr. Merritt emphasized.

The field also lacks robust evidence on whether to continue or temporarily stop beta-blockers during acute worsening of heart failure, he said. For patients with hypotension without organ hypoperfusion, the beta-blocker dose might be reduced. But in the “extreme example of cardiogenic shock, it seems logical that beta-blockers should be temporarily discontinued, although some cardiologists may just reduce the dose of beta-blocker and add a non-beta-agonist inotrope, such as milrinone.”

Another question is how to manage beta-blockers in patients with chronic heart failure and reduced ejection fraction who are hospitalized for other reasons, such as sepsis or severe blood loss. “Generally, if a patient is hemodynamically unstable or if you are concerned for impending decompensation, it makes sense to temporarily hold beta-blockade,” Dr. Merritt said. “Again, there is no randomized evidence to guide us.”

Coronary artery disease

For patients with coronary artery disease who have neither heart failure nor a history of MI, recent research suggests that beta-blockers don't prevent cardiovascular events. There are post-hoc analyses of trials, observational studies, and recent meta-analyses to support this conclusion, according to William Boden, MD, scientific director of the Clinical Trials Network, MAVERIC, at the VA New England Healthcare System and professor of medicine at the Boston University School of Medicine. “There is mounting evidence that we need to be more selective and judicious in prescribing beta-blockers to patients hospitalized for cardiovascular disease,” he added.

He cited a study of over 750,000 patients, published in the August 22, 2016, JACC: Cardiovascular Interventions in which beta-blockers failed to improve cardiovascular outcomes 30 days and three years after elective percutaneous coronary intervention. Findings like these raise questions about extrapolating the “putative benefits of beta-blockers to all patients with stable coronary artery disease,” Dr. Boden said. Still, this population is increasingly receiving beta-blockers, he noted. “For years, clinicians have extrapolated the evidence of beta-blocker benefit from older post-MI trials and applied it to all patients with coronary artery disease,” he wrote in an editorial that accompanied the study.

This overprescribing results mainly from guidelines that broadly recommend beta-blockers in coronary artery disease, despite a lack of rigorous data showing that they benefit the large subsets of patients without AMI, reduced left ventricular systolic function, or ongoing angina, according to Dr. Boden. He finds it very hard to accept such recommendations, he said. “If we are supposed to practice evidence-based medicine, the evidence is either weak or lacking that the majority of patients with coronary artery disease derive any meaningful clinical benefit from beta-blockers.”

Dr. Boden does recommend considering beta-blockers in coronary artery disease with serious or complex polymorphic or sustained ventricular arrhythmia, he said. “Most of these patients would also be candidates for an implantable cardioverter/defibrillator to prevent sudden cardiac death, but even with an ICD implanted in such patients, I would favor continuing a beta-blocker indefinitely.”

Who does what?

Shifting evidence about the risks and benefits of beta-blockers highlights the need for hospitalists to seek input from multiple sources when deciding how to treat complex cases, the experts said.

“Collaborative decision making among physicians is generally the best approach,” Dr. Steinman stressed. “By the same token, we should not simply be punting decisions to someone else—that often results in nobody having ownership of the patient.”

Accordingly, cardiologists should help guide decisions for patients with advanced heart failure who probably cannot tolerate beta-blockade or who have contraindications such as borderline hypotension or heart block, said Dr. Merritt. But hospitalists should take the lead in prescribing beta-blockers for straightforward indications, such as heart failure in the setting of reduced ejection fraction, he said.

Hospitalists should also talk with primary care clinicians about the reasons for beta-blockade and the importance of titrating medication if needed, he added. Primary care clinicians also can help hospitalists understand potential treatment barriers, such as past issues with cost, health knowledge, or adherence, he said.

Dr. Steinman agreed, noting that physicians make mistakes when they don't consider or have access to their patients' full story. “The primary care clinician can provide valuable insights into a patient's goals of care, abilities at home, and so forth,” he said. “The hospitalist can use this information to help make a high-quality, patient-centered treatment decision in the acute setting.”