Beta Blockers of No Use in Stable CAD Patients

October 02, 2012

October 2, 2012 (New York, New York) — New registry data indicate that beta blockers do not appear to be of any benefit in three distinct groups of stable outpatients: those with coronary artery disease (CAD) but no history of MI; those with a remote history of MI (one year or more); and those with coronary risk factors only [1].

Lead author Dr Sripal Bangalore (New York University School of Medicine, NY) told heartwire that the evidence for beta-blocker use has mainly been based on old post-MI trials that antedate modern reperfusion or medical therapy and heart-failure trials. People have extrapolated from these trials and assumed that the drugs are also beneficial in those with CAD and even those with just risk factors for CAD, he says, but it is not known if this is justified. Bangalore and colleagues decided to investigate further; they report their findings in the Journal of the American Medical Association, published online October 2, 2012.

Whether they used beta blockers or not in each of these three distinct patient cohorts, we did not see an association with reduced CV events, even in the prior-MI group.

"What we found was pretty interesting. Whether they used beta blockers or not in each of these three distinct patient cohorts, we did not see an association with reduced CV events, even in the prior-MI group. And for some of the outcomes, being on a beta blocker was associated with worse outcomes; for example, there was an increased risk of the primary composite end point--CV death, nonfatal MI, or nonfatal stroke--in patients with just risk factors but no CAD," he notes.

He says that the answer to how long a patient should continue to take a beta blocker after an acute MI is not really known: "As of now, we don't have enough data to answer this. If a patient after a year [following MI] can no longer tolerate beta blockers for any reason, and they don't have heart failure, the data would suggest there is no harm in stopping. If they do have heart failure, however, I would be more inclined to push them a bit further and say, 'This is a great medication; it saves lives.' "

To this end, he stresses that "it is important to understand what this study is not about. It's definitely not about patients who come in after an acute MI or those who have HF--we know there is plenty of data to suggest that beta blockers are beneficial in HF--and also it's not about patients who are on a beta blocker for any other reason, be that for arrhythmias or migraine prophylaxis."

REACH Registry: Data in Almost 45,000 Patients Show Mostly No Benefit

Bangalore and colleagues analyzed data from the Reduction of Atherothrombosis for Continued Health (REACH) registry of 44 708 participants, 14 043 (31%) of whom had prior MI, 12 012 (27%) had documented CAD but without MI, and 18 653 (42%) had CAD risk factors only.

The primary study outcome was a composite of CV death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure; and there were a number of tertiary outcomes. Overall median follow-up was 44 months.

Researchers found that event rates were not significantly different in patients with vs those without beta-blocker use for any of the outcomes tested, even in the prior-MI cohort (16.9% vs 18.6%; hazard ratio [HR] 0.90, p=0.14).

In the CAD-without-MI group alone, rates of the primary end point were not significantly different among those with vs those without beta-blocker use (12.9% vs 13.6%; HR 0.92, p=0.31). And for the secondary end point in this patient group, outcomes were actually worse among those who used beta blockers compared with those who didn't (OR 1.14, p=0.01); this was also the case for the tertiary outcome of hospitalization (OR 1.17, p=0.01).

The same applied to the cohort with risk factors alone, in which rates of the primary end point were higher among those who used beta blockers than those who didn't (14.2% vs 12.1%; HR 1.18, p=0.02), as were rates of the secondary outcome (22.0% vs 20.2%; OR 1.12, p=0.04), but not the tertiary outcomes of MI and stroke.

Randomized Clinical Trials Needed to Define Subgroups of CAD Patients Who Will Benefit

Bangalore says there is somewhat of a disconnect between what current guidelines recommend--which is broadly in line with what he and his colleagues found--and what doctors on the ground are actually doing.

The most recent American Heart Association guidance on secondary prevention, for example, gave beta blockers only a class IIa recommendation for longer-term therapy and a class IIb recommendation for patients with coronary or other vascular disease, note he and his colleagues. And the latest European Society of Cardiology guidelines recommend long-term beta-blocker therapy only in patients with reduced left ventricular systolic dysfunction (class I), he says.

The message is we do need randomized trials in this era of modern medical and reperfusion therapy, even in patients with prior MI, to actually define who is best for beta-blocker therapy and to identify the optimal duration of treatment.

"Though the guidelines are kind of aligned with what we are showing, in practice that's not true. It's common to see beta blockers being prescribed because of the perception that they are perhaps beneficial. But we should be extra careful in making those extrapolations," he told heartwire .

"There are a lot of patients who have had even a remote MI and who are still on beta blockers. And they are prescribed even for people who have had PCI and CABG but who have not had an MI," he notes. And he adds that this drug class is still widely used for high blood pressure despite the fact that it has been downgraded by many hypertension societies to a fourth-line agent for the treatment of this condition.

"The message is we do need randomized trials in this era of modern medical and reperfusion therapy, even in patients with prior MI, to actually define who is best for beta-blocker therapy and to identify the optimal duration of treatment," he concludes.

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

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