A class of drugs called beta-blockers — used for decades as a first-line treatment after a heart attack— doesn’t benefit the vast majority of patients and may contribute to a higher risk of hospitalization and death in some women but not in men, according to groundbreaking new research.

“These findings will reshape all international clinical guidelines on the use of beta-blockers in men and women and should spark a long-needed, sex-specific approach to treatment for cardiovascular disease,” said senior study author Dr. Valentin Fuster, president of Mount Sinai Fuster Heart Hospital in New York City and general director of the National Center for Cardiovascular Investigation in Madrid.

Women with little heart damage after their heart attacks who were treated with beta-blockers were significantly more likely to have another heart attack or be hospitalized for heart failure — and nearly three times more likely to die — compared with women not given the drug, according to a study published in the European Heart Journal and also scheduled to be presented Saturday at the European Society of Cardiology Congress in Madrid.

“This was especially true for women receiving high doses of beta-blockers,” said lead study author Dr. Borja Ibáñez, scientific director for Madrid’s National Center for Cardiovascular Investigation.

“The total number of women in the clinical trial was the largest ever included in a study testing beta-blockers after myocardial infarction (heart attack), so this is a significant finding,” said Ibáñez, a cardiologist at Madrid’s Jiménez Díaz Foundation University Hospital.

The findings, however, only applied to women with a left ventricular ejection fraction above 50%, which is considered normal function, the study said. Ejection fraction is a way of measuring how well the left side of the heart is pumping oxygenated blood throughout the body. For anyone with a score below 40% after a heart attack, beta-blockers continue to be the standard of care due to their ability to calm heart arrhythmias that may trigger a second event.

Still, the drug can have unpleasant side effects, said Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health in Denver.

“The drugs can lead to low blood pressure, low heart rate, erectile dysfunction, fatigue and mood swings,” said Freeman, who was not involved in the research. “Anytime we use these drugs, we always have to balance risk versus benefit.”

Why would women be more susceptible to harm from beta-blockers than men?

“That’s actually not surprising,” Freeman said. “Gender has a lot to do with how people respond to medication. In many cases, women have smaller hearts. They’re more sensitive to blood pressure medications. Some of that may have to do with size, and some may have to do with other factors we have yet to fully understand.”

In fact, because early research on the heart focused on men, it took medical science years to discover that heart disease presents differently in women. Men typically have plaque buildup in their major arteries and experience more traditional signs of a heart attack such as chest pain. Women are more likely to have plaque in the heart’s smaller blood vessels and can have more unusual symptoms of a heart attack such as back pain, indigestion and shortness of breath.

The analysis on women was part of a much larger clinical trial called REBOOT — Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction — which followed 8,505 men and women treated for heart attacks at 109 hospitals in Spain and Italy for nearly four years.

Results of the study were published in The New England Journal of Medicine and also presented at the European Society of Cardiology Congress.

None of the patients in the trial had a left ventricular ejection fraction below 40%, a sign of potential heart failure.

“We found no benefit in using beta-blockers for men or women with preserved heart function after heart attack despite this being the standard of care for some 40 years,” said Fuster, former editor-in-chief of the Journal of the American College of Cardiology and past president of the American Heart Association and the World Health Federation.

That’s likely due to advances in medication treatment such as the immediate use of stents and blood thinners after patients arrive at the hospital. In fact, most men and women who survive heart attacks today have ejection fractions above 50%, Ibáñez said.

“Yet at this time, some 80% of patients in the US, Europe and Asia are treated with beta-blockers because medical guidelines still recommend them,” he said. “While we often test new drugs, it’s much less common to rigorously question the continued need for older treatments.”

While the study did not find any need to use beta-blockers for people with a left ventricular ejection fraction above 50% after a heart attack, a separate meta-analysis of 1,885 patients published Saturday in The Lancet did find benefits for those with scores between 40% and 50%, in which the heart may be mildly damaged.

“This subgroup did benefit from a routine use of beta-blockers,” said Ibáñez, who was also a coauthor on this paper. “We found about a 25% reduction in the primary endpoint, which was a composite of new heart attacks, heart failure and all-cause death.”

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