Blanket benefit of beta-blockers put in doubt
Beta-blockers’ status as a standard of care for coronary artery disease (CAD) patients with a previous MI, with no history of MI and those with CAD risk factors only may take a tumble, based on results of a study published Oct. 2 in the Journal of the American Medical Association.

“We wanted to see if the effect of beta-blockers would differ in patients with prior MI, in patients with coronary issues but no prior history of heart attacks or those with risk factors alone,” said the study's lead author, Sripal Bangalore, MD, MHA, in an interview with Cardiovascular Business. “We were expecting to find a difference, but one thing that surprised us was the consistency that there was no benefit in any of these three groups.”  

Bangalore, director of research of the cardiac cath lab and the director of the Cardiovascular Outcomes Group at New York University School of Medicine in New York City, and colleagues designed a longitudinal, observational study using REACH (Reduction of Atherothrombosis for Continued Health) registry data to examine the association between beta-blocker use and cardiovascular events in these three patient groups. They noted that the evidence for beta-blocker treatment for these patients was based on post-MI trials that predated modern reperfusion or medical therapy and heart failure studies, and then extrapolated to CAD patients and patients at risk of CAD.

Bangalore and colleagues identified 44,708 patients in the REACH database who had been enrolled in 2003 and 2004 and divided them into three groups: those with prior MI (14,043 patients, 30 percent without beta-blocker use), those with documented CAD but without MI (12,012 patients, 40 percent without beta-blocker use) and those with CAD risk factors only (18,653 patients, 75 percent without beta-blocker use). The overall median follow-up was 44 months.

The primary outcome was a composite of cardiovascular death, nonfatal MI or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. They used propensity score matching for the primary analysis, which included 21,860 patients.

They found that event rates did not differ significantly between patients using or not using beta-blockers. In patients with a prior MI, the event rates were 16.93 percent for those treated with beta-blockers vs. 18.6 percent for those not using beta-blockers for the primary outcome. Event rates were 30.93 percent vs. 33.12 percent, respectively, for the secondary outcome.

In patients with CAD and no prior MI, the event rates were 12.94 percent vs. 13.55 percent, respectively, for the primary outcome. Event rates were higher for beta-blocker users for the secondary outcome, at 30.59 percent vs. 27.84 percent. In patients with risk factors only, event rates were higher among beta-blocker users, at 14.22 percent 12.11 percent, for the primary outcome, and 22.01 percent vs. 20.71 percent for the secondary outcome.    

“In this analysis of 44,708 patients from the REACH registry, beta-blocker use was not associated with a lower incidence of cardiovascular events among individuals with a prior history of MI, among individuals with CAD but no MI history or among individuals with risk factors only for atherosclerotic disease,” Bangalore and colleagues wrote.

The findings challenge the notion that the benefits seen with beta-blocker use for patients experiencing an MI or patients with heart failure can be extrapolated as a preventative strategy for other sets of patients. “From this analysis, we know that extrapolation is not justifiable,” Bangalore said, adding that it may go against the grain for some physicians. “I am sure we will get a lot of pushback. But at least it sets the stage for a debate.”

Bangalore emphasized that beta-blockers provide benefit for patients with heart failure, who present acutely with MI or who have arrhythmias. The results from this analysis apply only to the patient groups studied and to the outcomes specified, he cautioned.

The use of beta-blocker therapy also has been clarified in recent secondary prevention guidelines, the study authors pointed out. The American Heart Association and American College of Cardiology, for instance, gave beta-blockers a Class I recommendation as a treatment for patients with left ventricular ejection fraction of 40 percent or less with heart failure or patients with prior MI, unless contraindicated, in their 2011 update (Circulation 2011;124:2458-2473). But guideline writers termed beta-blocker therapy as optional (Class IIa or IIb) for patients without the Class I indications.  

The study’s findings both reinforce guideline recommendations and also provide evidence that may inform future modifications, Bangalore said. Despite propensity score matching, though, the study had limitations that included the potential for unmeasured confounders. Bangalore and colleagues are calling for additional research such as a randomized trial.