Analysis Questions Beta-blockers in Stable CHD Patients

July 14, 2014

HELLERUP, DENMARK — A new analysis of patients with newly diagnosed coronary heart disease (CHD) suggests that the benefits of beta-blockers in this setting appear relegated only to those with a recent MI[1].

In a meta-analysis of more than 26 000 patients discharged after their first CHD event, defined as either acute coronary syndrome or coronary revascularization, the use of beta-blockers was associated with an overall 10% lower risk of mortality and an 8% lower risk of death or MI. The benefit, however, extended only to those with a recent MI.

"The evidence for or against beta-blockers in patients with stable ischemic heart disease is really sparse," said lead investigator Dr Charlotte Andersson (Gentofte University Hospital, Hellerup, Denmark). "The clinical guidelines say that beta-blockers may be considered for patients with coronary artery disease, but the evidence underlying the recommendation is not based on randomized clinical trials. It's a IIb recommendation."

To heartwire , Andersson said there are randomized clinical trials showing that beta-blockers can reduce cardiac events and mortality among recent MI patients and those with heart failure with systolic dysfunction. In those with stable CHD, however, beta-blockers have been shown only to reduce angina, and no trials have shown the drugs reduce cardiac events. Instead, much of the support for beta-blockers in stable CHD patients has been extrapolated from the MI/heart-failure patients.

"Most of the clinical trials were carried out 20 years ago," said Andersson. "A lot of things have happened in cardiovascular medicine since then. One of the most important things is revascularization. Today, most people are undergoing a fast primary PCI, which is one of the biggest differences from the past. I don't think, in all cases, we can extrapolate those prior findings to today's contemporary medicine. And when it comes to patients with stable coronary heart disease, there hasn't been a long-term randomized trial carried out in this specific group of patients."

In addition to the changes in invasive revascularization strategies, patients today are treated with more potent drug therapies, including antiplatelet medications and statin therapy. These changes call into question how applicable prior studies of beta-blockers are in the stable CHD setting, noted Andersson.

In an editorial accompanying the study[2], Dr Philippe Gabriel Steg (Hôpital Bichat, Paris, France) and Dr Ranil De Silva (Royal Brompton and Harefield National Health Services Trust, London, UK) say the new analysis "strengthens the view that systematic use of beta-blockers is not mandated for all patients with stable coronary artery disease, especially in the absence of previous myocardial infarction."

Data From the Kaiser Permanente Database

The researchers analyzed patient records over an eight-year period from the Kaiser Permanente Northern California healthcare system. They identified 26 793 patients hospitalized for non-ST-segment-elevation MI (NSTEMI), STEMI, or unstable angina or who underwent coronary revascularization with CABG surgery or PCI. Of the 26 793 patients, 19 843 were started with a beta-blocker within seven days of discharge for the initial CHD event.

After an average follow-up of 3.7 years, 6968 patients died or had an MI. As noted, beta-blocker therapy was associated with an overall reduction in the risk of death and a reduction in the risk of death/MI. When the researchers stratified the patients into two groups—those with MI as the index event and those without—they found that the benefit of beta-blockers extended only to those with a recent MI. For those with a recent MI, the use of beta-blockers was associated with a significant 15% reduction in the risk of death and a 13% reduction in the risk of death or MI.

"There was a significant difference in outcomes with beta-blocker treatment, where we confirmed what prior clinical randomized clinical trials have found, that beta-blockers in patients with a recent MI had a lower risk of death or recurrent MI," said Andersson. "Among people with more stable coronary heart disease, we found no effect at all."

In 2012, an analysis of the Reduction of Atherothrombosis for Continued Health (REACH) registry, which included 44 708 participants and was reported by heartwire , also showed that beta-blocker therapy in stable coronary artery disease patients did not provide any benefit.

Given the observational nature of their analysis, the usual caveats apply, according to Andersson. She notes the study did not show beta-blockers caused harm in the stable patients and that it is still too early to recommend that stable CHD patients, aside from those with an MI, not take beta-blockers following their index event. "But these data, and a couple of other recent observational studies, really do call for a randomized clinical trial in this setting," she said.

For Steg and De Silva, given the absence of mortality/MI benefit in the stable CHD patients, they write that beta-blockers should be used only for the symptomatic relief of angina, as the American College of Cardiology/American Heart Association and European Society of Cardiology (ESC) currently recommend. "This recommendation will come as welcome relief for stable coronary artery disease patients, the vast majority of whom are asymptomatic and are prescribed a plethora of pharmacologic agents, including antiplatelet therapy, statins, and blockade of the renin-angiotensin system to improve prognosis."

For the patient with recent MI, though, the routine use of beta-blockers "seems reasonable," they write, although there is still some question of how long these patients should receive the drugs if they are without symptoms and left ventricular dysfunction. The current guidelines for MI patients state three years of beta-blocker treatment after the clinical event, but if side effects occur, Steg and De Silva say there is likely no reason to continue with the drugs.

This research was funded in part by a grant from the American Heart Association, with additional support by a grant from the Danish Agency for Science, Technology and Innovation. The authors have reported that they have no conflicts of interest. Steg has received research grants from Sanofi and Servier (to INSERM); personal fees from Amarin, 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; and is a stockholder in Aterovax. De Silva has reported that he has no conflicts of interest.

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