Swedish Study Adds to Evidence That Beta-blockers May Not Be Needed Long After MI

Yet another observational study, this one from the SWEDEHEART registry, is suggesting that for patients free from heart failure (HF) or left ventricular systolic dysfunction after MI, long-term use of beta-blockers may not improve clinical outcomes.

Over a median follow-up of 4.5 years, the risk of a composite of all-cause mortality, recurrent MI, unscheduled revascularization, or hospitalization for heart failure was no different between patients who were versus weren’t taking a beta-blocker a year after their MI (HR 0.99; 95% CI 0.93-1.04), lead author Divan Ishak, MD (Uppsala University, Sweden), and colleagues report in a study published online this week in Heart.

There also were no differences for any of the individual components of that endpoint, or for CV mortality or stroke.

Although beta-blockers have been a guideline-recommended treatment after MI for several decades, regardless of the presence of heart failure, their use is based on trials conducted at time when MI treatment was very different. Now, most patients are revascularized with PCI and receive multiple evidence-based medications for secondary prevention, and that has driven down the proportion of post-MI complications like heart failure.

Numerous observational studies have explored the utility of beta-blockers on top of contemporary MI treatment, with mixed results. The OBTAIN registry, for instance, showed a lower risk of mortality with versus without beta-blockers after acute MI, whereas numerous other studies, including the REACH and CLARIFY registries, have not demonstrated a difference in outcomes.

“So we need to go back and say, ‘Do we really need to prescribe beta-blockers to all of our patients?’” senior author Gorav Batra, MD, PhD (Uppsala University), told TCTMD. Although there is accumulating evidence that patients without heart failure or left ventricular systolic dysfunction may not, in fact, need beta-blockers over the long term, “we need to do randomized clinical trials to answer the question,” he added, noting that several such trials are ongoing—BETAMI, REDUCE-SWEDEHEART, DANBLOCK, REBOOT, and ABYSS.

We need to go back and say, ‘Do we really need to prescribe beta-blockers to all of our patients?’ Gorav Batra

Sripal Bangalore, MD (NYU Langone Health, New York, NY), lead author of the REACH analysis calling into question the impact of beta-blockers post-MI, agreed that clinical trials are needed to determine the efficacy of beta-blockers in patients with preserved ejection fraction long after an MI.

The results of the SWEDEHEART analysis are consistent with several studies from his group, including a 2014 meta-analysis published in the American Journal of Medicine, he told TCTMD via email. That analysis showed that in an era before reperfusion was widespread, beta-blockers reduced all-cause and CV mortality, with no such differences observed in the reperfusion era.

“Beta-blockers did reduce MI and angina at 30 days, but benefit seemed to be limited to the short term (30 days) and came at the expense of an increase in HF and cardiogenic shock,” Bangalore said.

He noted that beta-blockers come with side effects and tolerability is poor. Studies have shown that compliance falls with more time on the drugs, he added.

Still, strong recommendations for use of beta-blockers after MI remain in practice guidelines. “The data even from older RCTs on beta-blockers in those with preserved EF was weak at best,” Bangalore said. “We have been unduly influenced by the beta-blocker trials in patients with heart failure and have widely extrapolated it to patients without heart failure.”

It’s going to take results from randomized trials to change that, he said. “Fortunately, there are a few which are underway and we should have results in the next few years.”

The SWEDEHEART Registry

While awaiting randomized data, Ishak et al turned to the SWEDEHEART registry to explore the question. The current analysis included 43,618 patients (median age 64 years; 25.5% women) who were hospitalized for a first MI between 2005 and 2016 across 74 cardiac care units in Sweden and who did not have heart failure or left ventricular systolic dysfunction (LVSD). Follow-up began 1 year after the MI, at which point 78.5% of patients were receiving a beta-blocker and 21.5% were not.

Although the unadjusted rate of the primary composite outcome was lower among patients receiving beta-blockers during follow-up (18.9% vs 21.7%), the difference was not significant after inverse propensity-score weighting and multivariable adjustment. These findings were consistent across subgroups defined by sex, hypertension, diabetes, atrial fibrillation/flutter, previous MI, type of MI, and in-hospital PCI.\

We have been unduly influenced by the beta-blocker trials in patients with heart failure and have widely extrapolated it to patients without heart failure. Sripal Bangalore

“The results of our study address an existing gap in the current evidence and provide an insight into long-term optimal secondary prevention strategies for a large proportion of MI survivors—namely, patients with no heart failure or LVSD who may have longer survival compared with those who develop such complications after an MI,” the investigators write.

“As such, understanding the association between long-term beta-blocker use and CV outcomes in this group of patients has important implications in determining health policies and developing clinical practice guidelines, but also has an impact on patients’ health-related quality of life and compliance with other CV preventive therapies,” they say, noting that beta-blockers have been tied to several side effects that include depression and fatigue.

Awaiting the Trials

This study raises questions about guideline recommendations for beta-blocker use in all patients who have had an MI and who don’t have contraindications, according to Tom Evans, MBChB, and Ralph Stewart, MBChB, MD (both from Te Whatu Ora Health New Zealand Te Toka Tumai Auckland, New Zealand).

The analysis has several strengths, including the large sample size, a representative population, detailed information on the variables used for propensity-score adjustment, and assessment of outcomes from administrative data sets, they say in an accompanying editorial.

But there are limitations, too, they say, pointing to differences between groups in factors known to influence the risk of adverse CV events and the potential for residual confounding.

“Most patients take daily medications for many years after a myocardial infarction because they believe they are beneficial,” Evans and Stewart write. “The study by Ishak et al raises an important question directly relevant to the quality of care—do patients with a normal LV ejection fraction benefit from long-term beta-blocker therapy after myocardial infarction? To answer this question, more evidence from large randomized clinical trials is needed.”

Batra stressed that the results of this study should not be used to change clinical practice, but added that they “should be eye-opening and make us more interested in the upcoming trial results.”

He and his colleagues note, however, “the benefit with beta-blockers in the chronic phase beyond the first year might remain unknown and the long follow-up required to draw firm conclusions may be challenging to achieve in traditional RCTs.”

I think the data gives you license to sort of make a judgment. Jeffrey Goldberger

Jeffrey Goldberger, MD (University of Miami Miller School of Medicine, FL), commenting for TCTMD, said there are no good data on how long to treat lower-risk patients—ie, with preserved EF and no heart failure—with beta-blockers after an MI. But there is at least some evidence that beta-blockers at certain doses could be beneficial more than a year after the event, he said, pointing to a landmark analysis of the OBTAIN registry and an as-yet unpublished analysis based on a large Danish cohort.

For observational studies addressing this question, however, “you have to take them all with a grain of salt,” Goldberger said.

There are many studies showing that among patients who don’t have HF or low EF, “once you get beyond a certain period of time, it’s not clear that there’s a benefit,” he said. “And if it’s not clear that there’s a benefit and there’s potential harm, well then you have to really make a patient-by-patient decision about whether to continue the beta-blocker or not.”

On the other hand, “if there’s a potential benefit and there’s no harm, then of course you’d continue it, and if there’s only potential benefit and real harm then you’d make the decision not to continue it,” he said. “I think the data gives you license to sort of make a judgment. To put it in clinical trial terms, there’s equipoise I think at this point about taking somebody beyond 1 year after MI and saying I can choose to treat or I can choose not to treat. They would both be acceptable based on the existing data.”

Summing up the issue, Goldberger said “the state of evidence is still in favor of initiating beta-blocker therapy for all patients with myocardial infarction unless there are contraindications.”

As for how long to continue such treatment, “I think patients who have left ventricular dysfunction or heart failure should probably continue their beta-blocker indefinitely. I think the data’s pretty good for that,” he said. “And then I think the jury is out yet on whether the lower-risk patients who are revascularized and have preserved left ventricular function and no heart failure . . . need long-term beta-blocker therapy or not.”