ATLANTA — Beta blockers are a mainstay in cardiovascular treatment, frequently given to patients after heart attacks. But a new large trial turns that convention on its head, suggesting that the drugs may not in fact help many of these patients.
The trial, which enrolled about 5,000 patients who specifically had preserved ejection fraction after a heart attack, found that long-term treatment with beta blockers did not significantly reduce the combined risk of death or new heart attack, according to results being presented here Sunday at the American College of Cardiology conference and published in the New England Journal of Medicine.
Ejection fraction, the proportion of blood pushed out of the heart’s left ventricle with each heartbeat, serves as a measure of the heart’s squeezing function. This study defined preserved, or normal, ejection fraction as over 50%, though some other studies define it as over 40%.
The frequent use of beta blockers after heart attacks is based on research that was conducted decades ago, before advancements in procedures doctors now use to open blocked arteries. The drugs make the heart beat more slowly and are meant to lower stress on the heart, but they can have side effects, such as fatigue, weight gain, and sexual dysfunction.
These days, patients have smaller heart attacks with less injury to their heart, leading doctors to wonder if current guidelines, which recommend using beta blockers regardless of ejection fraction, still make sense. Observational studies have suggested beta blockers may not be useful for people with preserved ejection fraction, but the field had so far lacked large randomized trials looking at this question.
“This is one of those studies at ACC that I think is potentially practice changing,” said Kim Eagle, director of the Frankel Cardiovascular Center at the University of Michigan who wasn’t involved in the trial. It’s “a very important landmark study that will change the way patients who are currently managed with [heart attacks] are cared for.”
The trial enrolled patients mostly in Sweden, but also some in Estonia and New Zealand. The researchers followed patients for a median of three-and-a-half years.
Patients assigned to beta blockers had a 4% lower combined risk of death or new heart attack compared with patients who didn’t take the drugs, but this result was not statistically significant.
People on beta blockers also didn’t have a significantly lower risk of individual outcomes studied: death from any cause, death from cardiovascular causes, heart attack, hospitalization for atrial fibrillation, and hospitalization for heart failure.
The rate of events studied for safety — such as stroke, low blood pressure, and fainting — was similar between the two groups.
The researchers did see that a subgroup of people who were already taking beta blockers upon having a heart attack and then were assigned to take beta blockers in the trial had a higher risk of death or new heart attack, but the authors said that this was likely a spurious finding.
“This is only a subgroup analysis which does not have statistical power and there’s no plausible explanation in our study, this is why we believe it’s a play of chance,” Troels Yndigegn, the lead author and an interventional cardiologist at Lund University in Sweden, said over email.
The patients who weren’t on beta blockers did not receive a placebo drug, so it wasn’t a blinded study. That may have introduced some biases, but the authors said that it’s unlikely to have affected the hard outcomes of death, heart attack, and hospitalization that were studied.
There are also limitations on how generalizable this study is, given that it mostly enrolled patients in Sweden, said Anuradha Lala-Trindade, an advanced heart failure and transplant cardiologist at Mount Sinai in New York who wasn’t involved in the trial.
Additionally, only 22.5% of the study participants were women. There has historically been an under-representation of women in cardiovascular trials. Yndigegn, the lead author, said, “our study has a similar proportion of female patients as in other comparable materials.”
It’s yet to be seen how physician groups and guideline writers respond, but “I applaud the authors and the investigators because it takes courage to question old dogma,” Lala-Trindade said. “We’re in a completely different era and the patient population is entirely different as well, so it really does beg the question of what do we go on to accept and what do we have to retest.”
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