WASHINGTON – Physicians seldom prescribe beta-blockers post MI in the full doses shown to improve survival in the classic randomized clinical trials conducted several decades ago, according to a large new study – and that, as it turns out, is a very good thing.
Results of the OBTAIN (Optimal Beta-Blocker Therapy After Myocardial Infarction) registry indicate that 2-year mortality post MI is lowest in patients discharged on a dose that’s roughly just 25% of target doses established in the landmark randomized trials, Dr. Jeffrey Goldberger reported at the annual meeting of the American College of Cardiology.
Bruce Jancin/Frontline Medical News
Dr. Jeffrey Goldberger
Two-year mortality post MI discharge followed a J-shaped curve: It was lowest, at 9.4%, in patients on about 25% of the target dose, and worst, at 14.9%, among those on more than 50% of the target dose. Mortality was intermediate in those whose beta-blocker dose hovered around either 12% or 50%. And patients on any of these four commonly prescribed dosing regimens fared significantly better than those who weren’t discharged on a beta-blocker, whose 2-year mortality was 21.7%, reported Dr. Goldberger, professor of medicine at Northwestern University in Chicago.
"Based on these data, we feel that following an MI it is important to treat patients with a beta-blocker. However, achieving the target doses used in prior randomized clinical trials is neither necessary nor desirable," he declared.
Quality improvement initiatives implemented in the past decade have resulted in greater than 90% utilization of beta-blockers after MI. However, practice guidelines don’t recommend specific beta-blockers or target doses. The OBTAIN registry was created in order to pin down the optimal dosing. The study hypothesis was that achieving target doses would be associated with better survival than with lower doses. Not so, investigators discovered.
The OBTAIN registry included 7,057 acute MI patients enrolled at 26 participating centers. In-hospital mortality was 4.7%. Of those patients who survived to discharge, 91.5% left the hospital on a beta-blocker. Metoprolol was prescribed in two-thirds of patients. The second most frequently prescribed beta-blocker post MI was carvedilol, utilized in one-quarter of patients.
The target daily doses normalized to those established in the landmark randomized trials as having a survival benefit are metoprolol 200 mg, carvedilol 50 mg, atenolol 100 mg, bisoprolol 10 mg, propranolol 180 mg, and timolol 20 mg.
Thirty-seven percent of patients discharged on a beta-blocker were on roughly 25% of the target dose. Roughly 25% of patients were on 12% of the target dose, a similar proportion got 50% of the target dose, and a mere 13% got more than 50% of the target dose. Three weeks post discharge, three-quarters of patients were on the same dose as when they left the hospital. Half of the rest had been titrated to a higher dose, the other half to a lower one.
In a multivariate analysis adjusted for demographics, diabetes and other comorbid conditions, ST-elevation MI, in-hospital therapies and length of stay, and other discharge medications, patients discharged on a beta-blocker had a 38%-51% lower mortality than those not on a beta-blocker. The most common reason that patients weren’t on a beta-blocker at discharge was hypotension.
Session cochair Dr. Yochai Birnbaum observed that the landmark randomized trials showing a mortality benefit for post-MI beta-blocker therapy were carried out in an era before statins and other potent secondary prevention therapies.
"It might be that when we add more and more medications, there are some interactions that are unclear. Maybe the previous recommendations are no longer valid," said Dr. Birnbaum, professor of medicine at Baylor College of Medicine, Houston.
The OBTAIN registry was sponsored by the National Heart, Lung, and Blood Institute. Dr. Goldberger reported having no relevant financial relationships.