Clinical Challenges: Long-Term Beta-Blocker Use After Uncomplicated MI

Clinicians suspect that routine prescribing of beta-blockers to heart attack survivors without heart failure or left ventricular (LV) dysfunction is no longer needed in contemporary practice. As relevant trials remain years away from completion, however, clinicians must make do with the little evidence available.

For patients who have undergone prompt primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) and are left with normal ejection fractions and no residual severe, unrevascularized lesions, there is no convincing evidence that the standard use of beta-blockers to blunt sympathetic activation actually provides added benefit nowadays, according to Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston.

As late as 2009 in the REACH registry, for example, investigators couldn’t find a significant benefit associated with beta-blockers in stable coronary artery disease patients with normal LV function or peers with known prior MIs, Bhatt recalled.

Yet American guidelines continue to be informed by decades-old research — trials predating modern reperfusion and medical therapy — in recommending 3 years of beta-blocker therapy as secondary prevention for patients surviving an acute MI.

“The issue with beta-blockers is that the bulk of the studies were done in the 1970s and 1980s when the treatment of MI was vastly different, not just in reperfusion, but aspirin and statins weren’t available then. ACE [angiotensin-converting enzyme] inhibitors weren’t widely used then. All those things have changed,” said Jeffrey Goldberger, MD, of the University of Miami Health System.

“There are a number of different goals to treatment: to prevent recurrent ischemia, prevent arrhythmias, and other effects related to remodeling or infarction. Today, some of those things are not as relevant. [For example,] we don’t need to treat patients with high-dose beta-blockers to prevent ischemia because we can prevent that with other therapies like revascularization,” he explained.

The only randomized trials of late on the topic have focused on short-term beta-blockers in ST-segment elevation MI (STEMI).

Even if beta-blockers still confer cardiovascular benefits in the long run, there is the question of the right dose for maintenance.

“There’s not a randomized controlled trial that’s looked at this in a dose titration level. The studies that were done back in the 1970s and 1980s, they all targeted pretty hefty doses of beta-blockers. It was the predominant therapeutic agent then, and they were trying to get the most effect,” Goldberger said.

How long patients should be treated with beta-blockers after an MI is also unknown. “Clearly in the first year you see tremendous benefit for beta-blocker therapy. Beyond the first year, there’s still a lot of questions,” he added.

Without higher-quality evidence relevant to contemporary MI care, clinicians are left to defer to how things had been done since the 1980s.

“Standard of practice is still to prescribe beta-blockers after MI. I don’t think that’s changed. That’s the guideline recommendation,” Goldberger continued.

“Many patients are reflexively put on these agents after presenting with an MI, even without specific indications such as LV dysfunction,” Bhatt noted. “I wouldn’t call it inappropriate, as we don’t really know whether it is helpful, harmful, or neutral … But it is in need of further study.”

Beta-blocker utilization used to be a quality indicator until the uptake got so high in the 2000s that hospitals no longer needed it as a quality indicator.

Today, “I suspect it’s still going to be in that range,” Goldberger said, adding that lower doses of beta-blockers are likely favored now.

Based on results from the OBTAIN registry, he and his colleagues reported that patients seemed to benefit from beta-blockers after acute MI, but outcomes did not improve with higher doses that go above 25% of what had been studied in the old clinical trials.

It is “reassuring” that people get as much benefit from lower doses as they do in higher doses, he said. “The side effect profile at lower doses is going to be better.”

Although beta-blockers are reasonably well tolerated by most people, the potential side effects can include muscle weakness, erectile dysfunction, weight gain, and increased risk of new-onset diabetes. In the INVEST trial from 2003, atenolol recipients with hypertension trended toward more angina and strokes compared with the calcium channel blocker arm getting verapamil. Beta-blocker use was also tied to death and stroke after noncardiac surgery in the POISE study.

The good news is that the flimsy risk-benefit profile of beta-blockers in modern acute MI treatment may not be a problem for long.

In Europe, several randomized controlled trials have been started in order to answer the questions of how these drugs fit into modern heart attack care. These studies comparing beta-blocker therapy with no beta-blocker therapy include:

• REBOOT-CNIC: over 8,000 patients across Italy and Spain (estimated study completion in November 2024)

• BETAMI: 10,000 people at several hospitals in Norway (October 2023)

• DANBLOCK: over 3,000 patients across Denmark (December 2022)

Additionally, the AβYSS trial from France is testing beta-blocker withdrawal at the 6-month mark after an uncomplicated MI.

Regardless of the outcome of these trials, the mainstay drugs after MI will likely continue to be helpful for many patients.

“In patients with STEMI and LV dysfunction, beta-blockers and ACE inhibitors have an important, evidence-based role, but these generic medicines remain underutilized,” Bhatt pointed out.

“The same lack of data holds for ACE inhibitors in the setting of successful primary PCI and normal LV function, though there may be other indications for ACE inhibitors such as diabetes with proteinuria or hypertension,” he noted.