- Beta-blockers are a type of medication used after heart attacks.
- A recent study suggests that using beta-blockers does not improve certain outcomes after heart attacks where the left ventricular ejection fraction is preserved.
- Further analysis suggests that beta-blocker use may be harmful for women, especially for those who take beta-blockers at higher doses and for women who have preserved left ventricular ejection fraction.
Beta-blockers are a common group of medications that help manage several heart-related problems. Recent results from two studies are questioning the effectiveness and safety of beta-blocker use following certain heart attacks.
The primary study was published in the New England Journal of Medicine, and the sex-specific subgroup analysis was published in the European Heart Journal.
The original trial suggests that in people who experience a heart attack without reduced ejection fraction, beta-blockers don’t help to decrease risk for experiencing another heart attack, hospitalization from heart failure, or death from any cause.
The sex-specific analysis suggests that beta-blocker use among some women may actually be harmful. Beta-blockers may particularly increase mortality risk, especially for women with preserved left ventricular ejection fraction and those who receive greater doses of beta-blockers.
Research has started to suggest that beta-blockers don’t help after heart attacks where there isn’t a reduced left ventricular ejection fraction. The
The current research focused on beta-blocker use among participants following heart attacks, where left ventricular ejection fraction was over 40% before participants were discharged. This status indicates either a normal left ventricular ejection fraction or one that is only mildly decreased.
The open-label randomized trial included two groups of participants: one that received beta-blockers and one that did not. The main analysis included 8,438 participants, with about an equal number in each group. Some participants were already on beta-blockers before they were hospitalized.
All participants had experienced heart attacks. For those who received beta-blockers, they started them within two weeks of hospital discharge.
The median follow-up time was 3.7 years. Interestingly, the groups had very similar outcomes. The results indicated that using beta-blockers did not decrease the risk for the combined outcome of death from any cause, hospitalization for heart failure, or experiencing another heart attack compared to not taking beta-blockers.
Subgroup analysis suggests those with a specific heart attack type called a ST-segment elevation myocardial infarction might be at a higher risk of problems when taking beta-blockers. However, researchers suggest caution in interpretation.
Additionally, in the small group of participants who had mildly reduced ejection fraction, the number of events was lower in the beta-blocker group. However, this is difficult to interpret because of the small number of participants who fell into this category.
For the sex-specific subgroup analysis, researchers examined data from 1,627 women. During the median follow-up time, the primary endpoint was all-cause death, heart attack, or hospitalization because of heart failure. Women experienced higher rates of the primary endpoint than men. The difference in death rate between men and women did not reach a level of statistical significance.
The incidence rate of the primary endpoint among women participants was higher for women in the beta-blocker group than in the non-beta-blocker group. Basically, women had a 45% “higher relative risk.”
This finding was mainly because of higher death rates among women in the beta-blocker group compared to the non-beta-blocker group. The main reason for the higher death rates was higher cardiac mortality in the women’s beta-blocker group. In the other areas, like non-fatal heart attack, the rates were similar between women in the beta-blocker group versus the non-beta-blocker group.
Women participants also did not get as many guideline-based therapies, were older, and had more comorbidities than the men included in the study.
Among men and women participants who had mildly reduced ejection fraction, beta-blockers did not appear to affect the primary endpoint.
In contrast, women who had preserved left ventricular ejection fraction were at a higher risk for the primary endpoint: all-cause death, heart attack, or hospitalization from heart failure. The results also suggest that women on higher doses of beta-blockers were at an increased risk for the primary endpoint. These results were not true for men.
Overall, the authors suggest that the risk from beta-blockers for women “appeared to be confined” to those on higher doses and those who have preserved left ventricular ejection fraction.
There are limitations to this research. For one thing, there was a relatively small number of women in the study.
Sonya Babu-Narayan, clinical director at the British Heart Foundation and consultant cardiologist, noted that “Importantly, women with good heart function may have been worse off when they took beta-blockers after a heart attack. However, only around one in five study participants were women, underlying the need to recruit more women to cardiovascular trials.” Future research can also explore the reasons for the observed differences in outcomes between men and women.
Second, the research was conducted in Italy and Spain, so work in other countries with other samples may be helpful. It was an open-label study, meaning they didn’t hide who got what treatment. This could have impacted the results. However, the committee that examined the main clinical outcomes didn’t know which participants received beta-blockers and which did not.
Based on the follow-up methods, there is some possibility of missing data. The underlying assumptions of the study setup and how researchers conducted their analyses could also have impacted the results.
Some participants from the non-beta-blocker group were on beta-blockers during follow-up. Similarly, some participants in the beta-blocker group stopped taking beta-blockers during the follow-up. However, researchers believe that this did not impact the study’s conclusions. There was a longer enrollment period for the trial than the researchers had thought there would be.
The study protocol did not control the adjustment of beta-blocker doses, and “heart-rate monitoring was not required during follow-up.”
Finally, there is a risk that chance plays a role in the subgroup analyses. These findings mainly help guide future research. In the sex-specific paper, the authors acknowledge that they did not perform one particular adjustment that could have impacted results, and there may be a risk for residual confounding.
This research doesn’t show that beta-blockers are unhelpful when there is reduced ventricular ejection fraction. The original research notes that contemporary clinical trials have still shown benefit in this area. Babu-Narayan also noted that “More research is needed to further understand whether people with mildly reduced heart function benefit from beta-blockers.”
This research could lead to adjustments in the treatment of some heart attacks, and indicates the need for more research in women in this area. Patrick Kee, MD, PhD, cardiologist at Vital Heart & Vein in Houston, who was also not involved in the study, noted the following to Medical News Today:
“Both articles emphasize the need for reevaluation of current guideline recommendations for beta-blocker use post-MI [after heart attack] in light of contemporary cardiac care advancements. These findings challenge the current guideline recommendations…The significant disparity in beta-blocker efficacy and safety between men and women underscores the critical need for sex-specific considerations in cardiovascular pharmacotherapy, particularly in post-MI management.”
However, the research doesn’t undermine beta-blockers. Babu-Narayan noted the following to Medical News Today:
“It’s great to see studies like this, which do not simply follow the status quo, but take another look at commonly prescribed drugs. This ensures that the right patients are still getting the right treatments at the right time, in the context of modern-day medicine. If you’re prescribed a beta-blocker, this can be for many reasons, so it’s important that you continue taking it as medically advised by your doctor.”
— Sonya Babu-Narayan, clinical director at the British Heart Foundation
