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Beta-Blockers: No Broad Benefit in Stable Heart Disease?

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Beta-blockers might reduce the risk of death or a repeat event in the first years after a heart attack but not in other newly-diagnosed heart disease, an observational study suggested.

The versus nonusers after controlling for other factors, , of California's Stanford University, and colleagues found.

Action Points

  • Note that this cohort study suggests that beta blocker may not benefit patients with stable coronary artery disease.
  • Be aware that the exclusion of medically managed patients from the cohort may have biased these results leading to a falsely negative finding.

But those associations were only significant in secondary prevention after a recent MI, with adjusted hazard ratios of 0.85 for mortality (95% confidence limit 0.79-0.92) and 0.87 for death or MI (95% CL 0.82-0.93), the researchers reported in the July 22 issue of the Journal of the American College of Cardiology.

For other new-onset acute coronary syndrome patients the adjusted hazard ratio of death with beta-blocker use was 1.02 (95% CL 0.91-1.15), and for mortality or MI it was 1.03 (95% CL 0.93-1.13), suggesting no hint of benefit.

"Despite a general belief that beta-blockers may reduce cardiac events in these lower-risk patients, this indication for use of beta-blockers only has a Class IIB recommendation, on the basis of 'Level C' evidence -- expert opinion only," the researchers pointed out.

These drugs became a cornerstone of medical management of angina due to symptom relief and extrapolation of advantages in hard outcomes seen in trials after recent MI, heart failure, and reduced left ventricular function, without high-quality randomized trials in other stable heart disease, they noted.

That relatively weak foundation was challenged by observational findings from the REACH registry in 2012, showing no significant association between beta-blockers and cardiac events among patients with stable coronary heart disease.

The researchers suggested randomized trials to settle the net clinical benefit of beta-blockers in coronary disease without recent MI.

However, that's unlikely to happen in the real world, because an extremely large and expensive trial would be required, countered , of Hôpital Bichat in Paris, and , of Imperial College London.

They criticized Hlatky's study in an accompanying editorial, pointing to inability to fully adjust for confounding and uneven inclusion and event adjudication, as well as lack of data on "key clinical parameters, such as the presence and severity of anginal symptoms, ischemic burden, left ventricular function, and importantly, the type and dose of beta-blocker therapy."

Also, about 80% of the study's population of 26,793 consecutive integrated healthcare delivery system patients not on a beta-blocker in the prior year had been discharged after a first acute coronary syndrome.

The remaining 20% had been discharged after elective coronary revascularization.

That design excluded patients with incident, stable coronary artery disease managed medically without revascularization, the editorialists pointed out.

"Therefore, the results may be in part attributable to insufficient power to detect a benefit of beta-blockade in stable coronary artery disease patients without previous MI, and of uncertain relevance to the broader population of stable coronary artery disease patients not captured in the current analysis," Steg and De Silva cautioned.

Importantly, none of the available observational research has suggested harm from beta-blocker use in stable heart disease patients, they noted.

While the study affirms that the drugs are not mandated for all stable coronary artery disease patients, Steg and De Silva recommended a tailored treatment approach for symptomatic angina relief.

Finding the "most parsimonious" regimen that leaves patients symptom-free with minimal side effects "is particularly important, to ensure treatment compliance as well as optimize quality-of-life and clinical outcomes, especially in an era of constrained healthcare resources," they wrote.

From the American Heart Association:

Disclosures

The research was funded by grants from the American Heart Association and the Danish Agency for Science, Technology, and Innovation.

The researchers disclosed no relevant relationships with industry.

Steg disclosed relationships with Amarin, Aterovax, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers-Squibb, Daiichi- Sankyo, GlaxoSmithKline, Janssen, Eli Lilly, Medtronic, Merck-Sharpe- Dohme, Novartis, Otsuka, Pfizer, Roche, The Medicines Company, Sanofi, Servier, and Vivus.

De Silva disclosed no relevant relationships with industry.

Primary Source

Journal of the American College of Cardiology

Andersson C, et al "Beta-blocker therapy and cardiac events among patients with newly diagnosed coronary heart disease" J Am Coll Cardiol 2014; 64: 247-52.

Secondary Source

Journal of the American College of Cardiology

Steg PG, De Silva R "Beta-blockers in asymptomatic coronary artery disease: No benefit or no evidence?" J Am Coll Cardiol 2014; 64: 253-255.