ORLANDO – Low-dose beta-blockade appears to be at least as effective as standard full-dose beta-blocker therapy for cardioprotection in patients who’ve had an acute coronary syndrome, Dr. Jason E. Allen reported at the American Heart Association scientific sessions.
“This is an important observation, because in clinical practice patients often don’t tolerate high-dose beta-blockers. They prefer not to be on them. They experience hemodynamic issues like orthostatic hypotension and bradycardia. Plus, at times it’s important to have blood pressure room for other things – comorbid conditions like diabetes, where ACE inhibitors might also have an important role,” said Dr. Allen of Intermountain Medical Center in Salt Lake City.
Bruce Jancin/Frontline Medical News
Dr. Jason E. Allen
While beta-blockade is a cornerstone of optimal medical management for reducing cardiovascular events in patients with symptomatic coronary artery disease, the high doses recommended today are based on decades-old randomized trials, which may not be entirely applicable in the current era of advanced medical and interventional therapies. That’s why he and his coinvestigators conducted a retrospective observational study using the Intermountain Healthcare database for the years 1993-2013.
They identified 7,158 patients with angiographically documented CAD who were discharged on beta-blocker therapy following an ACS. Eighty-five percent were discharged on a low-dose beta-blocker, defined by investigators as 25% or less of standard-dose metoprolol tartrate at 200 mg/day or its equivalent. Only 15% were discharged on high-dose therapy, defined as at least 100 mg/day of metoprolol or its equivalent.
The study endpoint was the incidence of the composite endpoint of all-cause mortality, MI, or stroke during follow-up. Because the group on high-dose beta-blockers typically had higher baseline rates of hypertension and hyperlipidemia, and a higher body mass index, propensity scores were utilized to adjust for these differences in a Cox proportional hazards analysis.
The incidence of the composite major adverse cardiovascular event (MACE) outcome from discharge through 6 months of follow-up was 4.3% among patients on a low-dose beta-blocker, which was equivalent to but not statistically superior to the 4.6% rate in those on high-dose therapy.
Among patients who didn’t have a MACE event in the first 6 months of follow-up, the incidence during months 7-24 was 4.8% in the low-dose group and 5.7% in the high-dose group, which once again was not a statistically significant difference. Of note, rates of all three components of the composite endpoint were numerically lower in the low-dose group.
A third analysis was restricted to the 6,844 patients who never switched between low- and high-dose therapy during the entire 24-month follow-up period. The composite MACE rate was 8.9% in the low-dose group, which was statistically equivalent to the 9.7% rate in patients on high-dose beta-blocker therapy throughout.
Dr. Allen was quick to point out that an observational study such as this can’t provide definitive proof. That would have to come from a randomized, controlled trial of high- versus low-dose beta-blocker therapy for secondary prevention. Such a trial also would be helpful in determining the mechanism of the putative equivalence seen in the Intermountain Healthcare study.
Dr. Allen’s study was conducted with institutional funds. He reported having no financial conflicts.