40-year-old drug is back in the spotlight after yielding unexpected results

A 40-year-old heart medicine, known as beta-blockers, has stepped back into focus after a huge Scandinavian study tracked thousands of recent heart attack survivors. 

In more than 5,500 patients, long-term use of the drug made serious heart problems less likely for a specific group.

The trial looked at people who had a recent myocardial infarction, a heart attack caused by a blocked artery, but did not show clear signs of heart failure. 

Its results suggest that the question of who truly needs to stay on a beta-blocker after a heart attack is more complicated than many doctors once thought.

History of beta-blockers

For decades, doctors have prescribed beta-blockers to many heart patients, often almost automatically. 

“Evidence supporting beta-blocker therapy after MI was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies,” explained Professor Dan Atar from Oslo University Hospital Ullevaal (OUHU).

The work was led by John Munkhaugen, M.D., Ph.D., head of research and consultant in cardiology at Drammen Hospital, Vestre Viken Hospital Trust in Norway (VVHT) and professor at the University of Oslo. 

His research focuses on preventive cardiology and how everyday treatments shape long term heart outcomes.

Modern guidelines already agree that beta-blockers are crucial when the heart’s pumping strength is clearly reduced, measured as a “low left ventricular ejection fraction.” This refers to the share of blood pumped out with each beat. 

In people whose pumping strength looks normal, with no heart failure or rhythm problems, several expert groups have questioned whether staying on the drug for years really adds much.

What the new trial tested

In the BETAMI and DANBLOCK trials, researchers enrolled adults who had recently survived a myocardial infarction in hospitals across Norway and Denmark. 

Every participant had a left ventricular ejection fraction of at least 40 percent and no signs of heart failure, which meant their hearts were still pumping reasonably well.

Within the first couple of weeks after the heart attack, about half the patients were randomly assigned to long term beta-blocker treatment and the rest to no beta-blocker at all. 

Events like death, new heart attacks, strokes, heart failure, unplanned procedures to reopen arteries, and dangerous rhythms were tracked for a median of 3.5 years and compared using a hazard ratio.

Patients taking a beta-blocker had fewer events of death or serious cardiovascular complications than those who did not, with a hazard ratio of 0.85. 

The 95 percent confidence interval, from 0.75 to 0.98, indicates that this difference is unlikely to be due to chance alone.

What the team found

When researchers broke the outcome into pieces, they saw that new heart attacks occurred in 5.0 percent of patients on beta-blockers, compared with 6.7 percent in those not taking them. 

Rates of stroke, heart failure, unplanned coronary procedures, and serious rhythm disturbances stayed very low and quite similar between the two groups, and deaths from any cause were rare in both.

Importantly, the trial did not reveal any major safety problems with long term use in this selected group. 

Serious side effects strong enough to make patients stop the medicine were uncommon, which provides some reassurance for people already taking these drugs after a recent heart attack.

Why beta-blockers matter

For patients who leave the hospital with a heart that still pumps fairly well, doctors have struggled with whether a beta-blocker really improves survival or simply adds extra pills. 

This trial suggests that, at least for people with preserved or mildly reduced pumping function and no arrhythmia, an abnormal or irregular heart rhythm, the treatment can lower the chance of another major event.

The benefit is modest rather than dramatic, so the decision to continue or start a beta-blocker still needs to balance possible tiredness, low blood pressure, or cold hands against the reduction in risk. 

For many younger or higher risk patients, especially those with mildly weakened heart pumping, that tradeoff may still come out in favor of staying on the medicine.

Questions still remain

At almost the same time, another large meta-analysis, a study that combines data from several clinical trials, reported that beta-blockers did not improve survival or prevent new heart attacks in patients whose ejection fraction was at least 50 percent after a heart attack. 

That work pooled individual patient data from five randomized studies and painted a more skeptical picture for people whose hearts appear completely normal on pumping tests.

A separate project focused only on people with mildly reduced ejection fraction between 40 and 49 percent found clear benefit from beta-blockers in preventing repeat heart attacks and heart failure episodes. 

This pattern, where patients with slightly weakened hearts gain the most, is supported by pooled data from European and Japanese trials that were reanalyzed in detail.

Taken together, these mixed results explain why many guideline committees have not rushed to make sweeping changes for patients with normal heart function after a heart attack. 

Future research will probably focus on teasing apart which subgroups, defined by age, sex, heart pumping strength, and other illnesses, truly gain enough from beta-blockers to justify long term treatment.

For anyone recovering from a recent heart attack, the practical message is simple. 

Medication decisions should never be changed on their own, and the best next step is a detailed conversation with a treating cardiologist who can weigh personal risks and benefits.

The study is published in the New England Journal of Medicine.

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