Beta-blockers not beneficial beyond 1 year in stable MI : CLARIFY

Beta-blockers have no impact on mortality beyond 1 year in post-MI stable CAD (coronary artery disease) patients and offer no survival benefit in stable patients who have not had a myocardial infarction, according to a new study presented at European Society of Cardiology (ESC) Congress 2018.

The analysis that represents 5 years of follow-up in the large, multinational CLARIFY registry, also demonstrated that calcium channel blockers (CCBs) provide no protection mortality at any point.

“After 1 year following an MI, or in patients without prior MI, both beta-blockers and calcium antagonists may be used for symptom relief, but a mortality benefit should not be assumed,” Emmanuel Sorbets, Imperial College London, England, said in a session of ESC 2018.

Beta-blockers and/or CCBs are recommended as the first-line therapy for symptom relief in patients with stable CAD in the current clinical practice guidelines in Europe. In contrast. the U.S. guidelines recommend the beta-blockers preferentially, with CCBs used for symptom relief when beta-blockers are contraindicated or cause unacceptable side effects.

The problem, said Sorbets, is that there have never been large randomized trials to test the prognostic effects of beta-blockers in this patient group and instead, recommendations have been drawn from meta-analyses using data extracted from the acute MI setting or from observational studies. For the CCBs, the only randomized trials in stable CAD are outdated and there are no large observational analyses.

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CLARIFY is a prospective, longitudinal registry tracking stable CAD patients in 45 countries. The current analysis enrolled between 10 and 15 consecutive patients being treated by nearly 3,000 physicians between November 2009 and June 2010 then followed them for 5 years. In all, 22,006 patients were initiated on beta-blockers and 22,004 on a CCB. To be included, patients had to have had at least one of the following: prior MI (> 3 months), prior revascularization (> 3 months), proven symptomatic myocardial ischemia, and/or angiographic coronary stenosis >50%.

The trialists excluded patients with severe heart failure and other conditions “interfering with life expectancy.”

Key Findings:

• Over 5 years of follow-up, there were no differences in the rates of all-cause death (the primary endpoint) or of CV death/nonfatal MI according to whether or not patients were given baseline beta-blockers, or whether or not they were started on CCBs.


• In further analyses that looked at the time since MI a significant reduction in all-cause death, CV death, and CV death/nonfatal MI among patients whose MI had occurred within the previous year (7% versus 10.3%; 95% CI 0.50-0.91) was found.


• For patients whose MIs had occurred beyond 1 year, no benefits of beta-blockers were seen.


• By contrast, when the same time-since-MI model was used to compare CCB versus no-CCB use, no differences were seen for any of the endpoints, regardless of the number of months or years that had elapsed since myocardial infarction.


• In additional analyses that considered drug use over time, and that adjusted for additional risk factors, no benefits were seen for use of beta-blockers or CCBs versus nonuse.

Eva Prescott, Bispebjerg Hospital, København, Denmark, one of the trial discussants, called the CLARIFY study “a very timely analysis because of discussion about beta-blockers and particularly after MI. The guidelines don’t agree, they’re not sure what they should recommend and even for non-STEMI, there’s not a clear recommendation for beta-blockers.”

The problem with observational studies, she continued, is that it’s not possible to completely adjust for the reasons why patients were or were not given a beta-blocker to begin with. “Do you really think, based on observational data,” Prescott asked, “that we can conclude that we should be giving a beta-blocker, at least for the first year after a myocardial infarction? Are you actually sure that if you start a beta-blocker early after myocardial infarction that you should continue to have a benefit?”

In response, Sorbets conceded that only a randomized controlled trial could decisively settle this question but added that there are no such trials and little likelihood that one will ever be done. “I can ask also, why continue beta-blockers over time? There is no data to do that, yet we still do that. For now, there are several good registries that assessed the use of beta-blockers and they all say the same thing: after 1 year, it seems to be not that great,” he said.