Post-MI Beta-blocker Use Dropped During Metoprolol ER Shortage, but Outcomes Unaffected

During a shortage of metoprolol succinate extended-release (ER) tablets about a decade ago, use of any beta-blockers after MI declined, but population-level patient outcomes did not seem to suffer, a new study shows. Experts interviewed by TCTMD disagreed as to whether these findings offer any insights into ongoing debate over the value of beta-blockade following MI.

From February 2009 to June 2010, when availability of metoprolol ER was limited, there were reductions in the proportion of patients who filled a beta-blocker prescription in the 30 days after discharge and in adherence during the first year among those who initiated therapy, according to researchers led by Katsiaryna Bykov, PharmD, ScD (Brigham and Women’s Hospital, Boston, MA).

That did not translate into worse patient outcomes, however, with no change in 1-year rates of rehospitalization for MI or unstable angina compared with the preshortage period, they report in a study published in the October issue of Circulation: Cardiovascular Quality and Outcomes.

Beta-blockers in the post-MI setting have been called into question by some—but not all—studies in recent years. Asked whether the current study adds anything to this discussion, Bykov said the short answer is no because the study was not designed to look into that issue. Although one explanation for the study findings is that beta-blockers do not have a major impact on post-MI outcomes in the current era, she said, it is also possible that the study was simply underpowered to detect changes in outcomes because the population was relatively young and there weren’t that many events.

Commenting for TCTMD, Jeffrey Goldberger, MD (University of Miami Miller School of Medicine, FL), agreed that this study does not inform the discussion about the efficacy of beta-blockers after MI, but added that that is a real question in the field. Although the earliest trials of beta-blockers going back to the early 1980s showed that treatment dramatically reduced mortality, additional therapies have been introduced since then, such as acute PCI, statins, and ACE inhibitors. In the modern era, then, there is a question about whether beta-blockers are adding anything, Goldberger said.

He pointed out that an analysis of the OBTAIN registry, published by him and his colleagues in 2015, showed that discharge beta-blocker use was associated with lower mortality in patients with acute MI, with the apparent benefits seen at lower versus higher doses.

“Surprisingly for as long we’ve been using this medication there really still is a lot for us to learn about who benefits and what the right dose is,” Goldberger said, adding that new trials of post-MI beta-blocker use are needed.

In the meantime, however, beta-blockers are still guideline-recommended for patients who have had an MI, and Goldberger said that shouldn’t change just yet even in the presence of some uncertainty.

“We don’t have new clinical trial evidence that suggests that you shouldn’t use beta-blockers post-MI in any patient,” he said. “Until that’s available, until we know better, I don’t think it’s going to change practice patterns all that much, and certainly not guidelines.”

For Sripal Bangalore, MD (NYU Langone Medical Center, New York, NY), the current study on its own would not be enough to question the use of beta-blockers after MI. But in the context of other studies, he said, “this is another [piece of] evidence to say we need randomized trials to address this question.”

He noted that the ongoing REDUCE-SWEDEHEART trial is evaluating whether long-term beta-blocker therapy improves outcomes in patients with preserved ejection fraction after an MI, and that his team currently has a trial looking at continuing or withholding beta-blockers in a stable CAD population under review for funding by the National Heart, Lung, and Blood Institute.

“The bottom line is the question is open, it needs to be investigated, and hopefully future trials will give us an idea about how essential beta-blockers are,” Bangalore said.

Shortages Remain Common

Drug shortages are a persistent problem, but there is limited information on how they impact patient outcomes, Bykov said. And what few studies there are in the literature focus mostly on drugs used in acute—and not outpatient—settings.

“To our knowledge,” Bykov et al write in their paper, “ours is the first study to evaluate the impact of an outpatient drug shortage on long-term patient outcomes, using a population-based cohort with complete ascertainment of drug utilization and longitudinal follow-up.”

For the study, the investigators analyzed data from the Optum Clinformatics Data Mart, a large commercial insurance database, on 38,914 patients (mean age 60; 69% men) who were discharged after being hospitalized for MI between January 2006 and November 2012. The metoprolol ER shortage, which was caused by production interruptions at the facilities of two manufacturers, lasted from February 2009 to June 2010.

Before the shortage, 70% of patients filled a prescription for any oral long- or short-acting beta-blocker within 30 days of discharge, and that proportion fell to 62% during the shortage. Mean monthly adherence (proportion of days covered) among patients who initiated therapy declined as well, from 76% in the preshortage period to 70% during the shortage.

“These results were observed despite an increase in use of other beta-blockers, including generic metoprolol ER products that were not affected by recalls and a transient increase in brand metoprolol ER utilization,” the authors note.

Bykov said the drop-off could have been due to a disconnect between patients, pharmacists, and physicians. Patients might have gone to the pharmacy to fill their prescription only to be told that it was not available. Then, if neither patient nor pharmacist reached out to the physician to get a prescription for another beta-blocker, the patient didn’t get one.

Whatever the reason, the lower use of beta-blockers during the shortage period was not associated with an increase in the 1-year rate of rehospitalization for MI or unstable angina, which was 4.9% during the preshortage period, 4.4% during the shortage, and 3.8% after the shortage.

Better Communication Needed

To ensure that patients continue taking their prescribed therapies during shortages, Bykov said, “there has to be a better connection between pharmacists and providers or physicians.” Hospitals maintain strong connections between pharmacists and physicians and have preparedness plans for drug shortages, she added, but “I don’t think that necessarily happens in the outpatient setting.”

Patients, pharmacists, and physicians all have a role to play in making sure treatment regimens are not interrupted when there are shortages, she said.

“Pharmacists can probably do a better job keeping track if the patient doesn’t fill their prescriptions because there was a shortage, and then there could be a better connection between pharmacists and prescribers in terms of getting patients the therapy they need,” Bykov said.

Goldberger said physicians would typically prescribe another medication from the same class if there were a shortage of a certain medication, noting that the reduction in beta-blocker use during the shortage despite the availability of other beta-blockers indicates that “we have some problem with the feedback loop.”

The question now is “how do we deal shortages and how do we get the patients to the right treatment even if there are medication shortages,” he said, agreeing that patients, pharmacists, and physicians need to work together to address the issue.