Up the dose of beta-blockers after MI

THE results of a recent US study serve as a reminder that beta-blocker doses should be reviewed and increased to the target dose where possible in patients who have had a heart attack, says a leading Australian physician.

Associate Professor Ian Scott, director of internal medicine at Princess Alexandra Hospital in Brisbane, said beta-blockers should be up-titrated towards the dose reported in original trials, except in those patients with contraindications.

“Where patients can tolerate the recommended target dose, then that is the dose we should be trying to aspire to,” he said.

“But patients who don’t get into clinical trials are treated in real life and real-world practice, so there may be limitations on how high you can push the dose of beta-blocker.”

Professor Scott, who chairs the Brisbane Cardiac Consortium Clinical Support Systems Program, said clinicians may be prevented from increasing the dose to recommended levels if patients were older or had other health problems.

He was commenting on a study in the American Heart Journal which found that under-dosing of beta-blockers was highly prevalent among patients post-myocardial infarction and was a significant clinical issue.(1)

The study used the PACEmaker and Beta-blocker Therapy Post-Myocardial Infarction (PACE-MI) trial registry, a prospective registry that provides contemporary data on patterns of beta-blocker therapy post-MI, to evaluate dosing in 1971 patients at discharge after MI and 3 weeks later.

The average age of patients was 64 years and 48% had an ST-elevation MI.

At discharge, rates of beta-blocker use were 93%, with 20% receiving below 25% of target dose, 37% receiving 25% of target dose, 26% receiving 26–50% of target dose and only 17% receiving more than 50% of target dose. The researchers defined the target doses for the most commonly used beta-blockers; for example, metoprolol 200 mg/day, propranolol 180 mg/day and atenolol 100 mg/day.

Between discharge and 3 weeks, 76.4% had no change in dose, with 11.9% having their dose reduced and 11.6% increased.

Absence of hypertension, acute percutaneous coronary intervention, older age, and no angiotensin-converting enzyme inhibitor therapy were consistent predictors of treatment with very low beta-blocker doses.

“Until and unless it becomes clear that low-dose beta-blockers provide the same large benefit as the target doses used in clinical trials, every effort should be made to achieve target doses,” the authors said.

“As it seems unlikely that very low doses … will result in the full benefit achievable with higher doses, a new phase in the quality improvement programs to address this issue could have dramatic impact on survival of patients following MI.”

The authors said it had been known for more than 20 years that beta-blockers improved survival following MI.

However, they also noted that it was very important to avoid excessively rapid dose titration, as rapid titration to target dose therapy could be associated with harmful effects, including death and strokes.

Professor Derek Chew, Director of Cardiology at the Flinders Medical Centre in South Australia, said registries still showed that most drugs were underused and used at doses lower than tested in clinical trials.

“Registry patients have more comorbidities and are more intolerant to medications,” he said.

The evidence for beta-blocker use had weakened recently but the new study might at least increase awareness of the issue and lead to a call for better research evidence, Professor Chew said.

1. Am Heart J 2010; 160: 435-442.

Posted 25 October 2010