Study Questions Post-MI Beta-blocker Use: Increased HF Risk, No Mortality Benefit

July 07, 2014

NEW YORK, NY ( updated with commentary ) — A new meta-analysis with more than 100 000 study participants suggests that clinical guidelines recommending the use of beta-blockers in post-MI patients need to be "reconsidered"[1].

The conclusions of the researchers, led by Dr Sripal Bangalore (New York University School of Medicine, NY), are based on their findings showing that while beta-blockers reduce reinfarction and angina in the post-MI setting, there is no reduction in the risk of mortality. More important, the meta-analysis showed that the use of beta-blockers increased the risk of heart failure and cardiogenic shock.

"It's actually a quality metric," Bangalore told heartwire . "In other words, if a hospital discharges a patient with an MI without a beta-blocker they get penalized. It's actually a big deal. If you look at the evidence base, there is not much evidence to strongly support their use. There are a lot of patients who can potentially develop adverse events like cardiogenic shock or heart failure. I think the once-size-fits-all approach is definitely not the way to go."

Published online June 10, 2014 in the American Journal of Medicine, the meta-analysis included 60 clinical trials with 102 003 patients. The patients were stratified into two distinct eras: the reperfusion era, which included 12 trials of 48 806 patients treated in the modern era of thrombolysis and interventional procedures, and the prereperfusion era, which included 48 studies with 31 479 patients.

Currently, the American College of Cardiology Foundation/American Heart Association guidelines for treating STEMI state the use of oral beta-blockers within the first 24 hours is a class I indication. Intravenous beta-blockers are recommended (class IIa) for hypertensive patients or those having ischemia. However, as Bangalore and colleagues point out, the majority of data supporting the use of beta-blockers predate modern reperfusion therapy and current medical management strategies with statins and antiplatelet agents.

In their analysis, the researchers observed a significant interaction between clinical outcomes and reperfusion era. For example, in the prereperfusion era, which mainly included trials with intravenous beta-blockers, there was a significant 14% relative reduction in all-cause mortality, as well as a 13% relative reduction in cardiovascular mortality, a 22% reduction in MI, and a 12% reduction in angina. In this era, there was no increased risk of heart failure or cardiogenic shock.

The mortality benefit was not evident in the reperfusion era, although there was a 28% reduction in MI and a 20% reduction in angina. However, these reductions were traded off against a 10% increased risk of heart failure and a 29% increased risk of cardiogenic shock.

Included within their analysis was the METOCARD trial, a study that investigated the early use of intravenous metoprolol prior to primary PCI vs oral post-PCI use recommended by the clinical guidelines. That study showed that patients who received beta-blockers before PCI had significantly improved outcomes, including higher left ventricular ejection fractions and fewer heart-failure hospitalizations. However, as Bangalore pointed out, the METOCARD study compared the timing of beta-blocker use, not a strategy of beta-blockade vs no beta-blockers, which was the comparison in their analysis.

"That trial did not address what we were trying to ask," he told heartwire , "which was whether or not beta-blockers actually prevent deaths following myocardial infarction."

The researchers acknowledge the analysis of the prereperfusion era might have lacked sufficient power to detect a mortality difference, but they suggest that in this era, "lack of reperfusion and contemporary medical therapy likely resulted in extensive myocardial scarring, providing a substrate for reentrant circuits and fatal ventricular arrhythmias." Reperfusion reduces the likelihood of scars forming, they note, and this might be the reason for the differences between the two eras.

In the reperfusion era, with the increased risk of heart failure and cardiogenic shock, the risk/benefit ratio of using beta-blockers "no longer seems to be favorable," write Bangalore et al.

Bangalore has no conflicts of interest. Disclosures for the coauthors are listed in the paper.

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