Beta blockers are among the most trusted and most prescribed drugs in the pharmacy. This category of medications includes atenolol (Tenormin), carvedilol (Coreg), metoprolol (Lopressor, Toprol) and the granddaddy of them all, propranolol (Inderal). At last count, more than 25 million Americans take beta blocker medications every day. Many take such drugs for high blood pressure, though this use has fallen into disfavor as a first line treatment. Others are given beta blockers after heart attacks. The theory has been that such drugs will help protect the heart from overworking and reduce the risk of another myocardial infarction (MI). A new study in the New England Journal of Medicine (April 7, 2024) casts a cloud over this use. It will shock a great many cardiologists.
A Litte Beta Blocker History:
Initially, beta blockers were developed to treat chest pain (angina) and lower blood pressure. They are also used to control irregular heart rhythms. The scientist who developed propranolol, Sir James Black, was honored with the 1988 Nobel Prize for medicine because of this drug discovery.
What made the research so noteworthy was the concept of receptors. Propranolol blocks the effect of norepinephrine and epinephrine (adrenaline) on beta-adrenergic receptors. Think of it a bit like stuffing a wad of bubble gum into a lock in a door. The key (epinephrine) cannot get into the receptor (lock) to turn and open (activate) the door. In the case of the heart, epinephrine and norepi cannot stimulate the heart to beat faster and pump harder because a drug like metoprolol is blocking the receptors.
Sir James wrote that the beta blocker propranolol reduced the demand for oxygen in a compromised heart (Medical History, Jan. 1, 2006). Inderal was approved by the FDA in 1967.
The agency describes its approval this way:
“Propranolol…became the first non-selective beta-blocker, a class of drugs that can reduce the work of the heart, thereby reducing the risk of adverse cardiac events. Propranolol quickly became crucial for managing ischemic heart disease, arrhythmias, and myocardial infarction. However, in time it also proved useful in treating noncardiovascular conditions that are also exacerbated by adrenaline binding, such as migraines, essential tremors and anxiety disorders. However, because propranolol can induce chemical dependency, in 2010 FDA required it be labeled with a boxed warning advising against abruptly discontinuing use.”
The FDA Approved Propranolol for:
- High Blood Pressure
- Angina pectoris
- Atrial fibrillation
- Post heart attack (myocardial infarction) “…to reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.”
- Migraine
- Essential tremor
- Hypertrophic subaortic stenosis
- Pheochromocytoma
Beta Blockers After Heart Attacks May Not Always Be Beneficial:
Most cardiologists believe they must prescribe beta blockers after heart attacks! That’s because the Beta-Blocker Heart Attack Trial (BHAT) was published over 40 years ago (JAMA, March 26, 1982).
The authors concluded:
“Based on the BHAT results, the use of propranolol in patients with no contraindications to beta-blockade who have had a recent myocardial infarction is recommended for at least three years.”
As a result of that clinical trial and other research, guidelines usually require that physicians prescribe beta blockers after heart attacks. If a physician were to discharge a heart attack patient without a beta blocker on board, there could be a metaphorical spanking by an oversight committee.
New Research Questions the Value of Beta Blockers After Heart Attacks:
A new study published in the New England Journal of Medicine (April 7, 2024) challenges the long-held belief that beta blockers are always essential after heart attacks. Over 5,000 heart attack patients in New Zealand, Sweden and Estonia were randomized to receive either metoprolol or bisoprolol or no beta blocker treatment. The study started in September of 2017 and lasted until May of 2023. The median follow-up time was 3.5 years. It was funded by “the Swedish Research Council and others.” The researchers recorded whether study participants had a second heart attack or died during the study.
There was a slight difference between groups, with 7.9 percent of those on beta blockers experiencing a heart attack or death from any cause. In the no beta-blocker group, 8.3 percent met that fate. That difference is not significant.
The trial was distinguished by its long duration. It suggests that beta-blocker treatment will not improve survival after a heart attack for everyone. Some patients with low ejection fractions may benefit, though. You will read about that shortly.
Some health care professionals who are reading this heresy might take exception to my summary.
Here is the doctorspeak version from the researchers themselves:
“In this registry-based, prospective, randomized, open-label, parallel-group trial conducted across 45 centers, most of which were in Sweden, the early initiation of oral beta-blocker treatment after an acute myocardial infarction in patients with a preserved left ventricular ejection fraction did not lead to a lower cumulative incidence of death from any cause or new myocardial infarction (composite primary end point). In addition, no appreciable between-group differences were observed in the analyses of secondary efficacy and safety end points. After 1 year, the incidence and severity of symptoms appeared to be similar in the two groups among the patients in Sweden who attended registry follow-up visits and had symptoms assessed. The absence of an effect of beta-blocker treatment on the cumulative incidence of death or myocardial infarction appeared to be consistent across all prespecified subgroups.”
We know that is hard to understand. But the bottom line seems to be that in people with “preserved left ventricular ejection fraction” of at least 50%, beta blockers were not beneficial.
We won’t go into a detailed discussion of ejection fraction, but it relates to the pumping power of the heart. The authors state that “The efficacy of beta-blockers in patients with heart failure and reduced ejection fraction is well documented.” So patients and their families will want to ask a cardiologist about ejection fraction percentages before opting for beta blockers.
An Editorialist Comments on Beta Blockers After Heart Attacks:
An editorial in the New England Journal of Medicine (April 7, 2024) accompanies the research cited above. It is very circumspect. The author cites a familiar axiom:
“absence of evidence is not evidence of absence”
He goes on to state:
“Given the difficulty of unambiguously showing an absence of benefit with beta-blocker therapy and the limitations of a single, somewhat underpowered, open-label trial, it may be too early to cut beta-blockers from the ‘secondary prevention team’ definitively. While we await the results of the multiple upcoming trials reevaluating the role of beta-blockers in contemporary care, it may be prudent to place routine beta-blocker therapy after myocardial infarction on ‘injured reserve.'”
No one should ever stop a beta blocker suddenly! Doing so might trigger serous heart problems.
Not the First Time Researchers Have Questioned Beta Blockers After Heart Attacks:
Many doctors did not believe the results of an earlier study in the Journal of the American Medical Association (JAMA, Oct. 3, 2012). The investigators tracked 44,708 high-risk heart patients. These people had had a heart attack or were diagnosed with coronary artery disease (CAD). After roughly 44 months of follow-up, there was no evidence that beta blockers prevented second heart attacks, strokes or death due to cardiovascular causes.
The authors concluded:
“In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of β-blockers was not associated with a lower risk of composite cardiovascular events.”
What About Beta Blockers for High Blood Pressure?
After more than 50 years as a mainstay for the treatment of hypertension, beta blockers are losing their luster. The Cochrane Collaboration is an independent, highly regarded organization of outside experts who review the world’s evidence on drugs.
An analysis by Cochrane concluded that:
“Beta-blockers are not recommended as first line treatment for hypertension as compared to placebo due to their modest effect on stroke and no significant reduction in mortality or coronary heart disease” (Cochrane Database of Systematic Reviews, Nov. 14, 2012).
The article we cited above from JAMA (Oct. 3, 2012) also concluded:
“Based on this evidence, β-blocker therapy has been downgraded by the European Society on Hypertension, the American Heart Association, and others to a fourth-line agent for the treatment of hypertension.”
More recently, though, the European Society of Hypertension has “upgraded beta blockers, putting them on equal footing with thiazide diuretics…” and other blood pressure-lowering medications (Lancet, Nov. 11, 2023). The reason for the “upgrade” is because the Society believes beta blockers “are often used for many other clinical conditions commonly encountered with hypertension.”
But one of the authors of this article in the Lancet is Professor Franz Messerli, MD, HonD. He is one of the grand old men of hypertension treatment. We have had the honor of interviewing Dr. Messerli.
He and his colleagues conclude that the European Society of Hypertension upgrade might be premature:
“Compared with the other first-line antihypertensive drug classes, β blockers are significantly less effective in preventing stroke and cardiovascular mortality. To relegate β blockers to an inferiority status as previous guidelines have done was based on the evidence in aggregate, and still stands. No new evidence supports the switch of β blockers back to first-line therapy. We are concerned that this move might lead to widespread harm because of inferior stroke protection.”
Beta Blocker Side Effects:
Beta blockers can make breathing more difficult, especially for people who are susceptible to asthma. Other complications may include fatigue, dizziness, slow heart rate, depression, sleep disturbances, hair loss, digestive upset, weakness and sexual dysfunction.
I have long contended that such a list of adverse reactions is virtually meaningless. People glaze over after reading two or three of these side effects. It is why drug companies have no problem listing super scary complications on their prescription drug TV commercials. People just tune out things like cancer, heart attacks, strokes, kidney failure or death. It seems so abstract as to be meaningless.
That is why we have written about the beta blocker “blahs” and the beta blocker “blues.” Here are some articles you may find more relevant than a list of beta blocker side effects:
The Beta Blocker Blahs Can Be Debilitating
Is Your Blood Pressure Medicine Making You Sad and Depressed?
Is Your Medication Causing Nightmares?
Could Your Medicine Cause Hair Loss?
Final Words About Beta Blockers After Heart Attacks:
Every situation is different. Every patient is different! There are times when it is absolutely appropriate for doctors to prescribe beta blockers after heart attacks. Beta blockers may also be critical for patients with hypertrophic cardiomyopathy. We have no doubt that beta blockers have saved lives and should absolutely be prescribed.
But there are also times when beta blockers may cause problems. People with with lung problems, especially asthma, may have difficulty breathing when they take certain beta blockers. Some people are very sensitive to beta blockers and may get too big a dose. That can slow the heart rate into the danger zone. The beta blocker blahs/blues can make some people miserable.
That is why it is so important to have a frank discussion with the prescriber about the pros and cons of beta blockers. If it becomes necessary to stop such drugs with medical supervision, it must be done gradually to prevent serious cardiac complications. We have heard of heart attacks occurring when patients stop such drugs too quickly.
Share Your Experience:
Please share your own experience with beta blockers in the comment section below. You may also want to ask your doctor if she is aware of the research published in the New England Journal of Medicine (April 7, 2024). Once prescribers get in the habit of writing prescriptions for familiar medications, they may not spend a lot of time keeping up with the latest developments. That’s why we try to keep you informed.
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