rx perspective
Re-Evaluating Beta-Blocker Safety
A review of recent studies shows that many concerns are unwarranted.
By Paul J. Lama, M.D.

Even with the development of potent prostaglandin analogues, beta-adrenergic blockers remain a key treatment option for the management of glaucoma and ocular hypertension. They're close to prostaglandins in terms of efficacy, and have arguably unsurpassed ocular tolerability.

Nevertheless, many practitioners are concerned about the chronic use of beta-blockers because of the possibility of systemic side-effects. Many of these concerns, however, are based on unproven dogmas and non-peer-reviewed information -- and they're not supported by recent clinical data.

Benefits for the Heart

Most of us were taught that beta-blockers should be avoided in patients with congestive heart failure (CHF) and symptomatic bradycardia, as well as more advanced degrees of heart block. However, recent data from randomized placebo-controlled trials have provided incontrovertible evidence that beta-blockers cause a reduction in mortality and improve functional status in patients with CHF.

In fact, the American College of Cardiology now recommends that all patients with depressed left ventricular function, when clinically stable, should be initiated on beta-blocker therapy -- whether or not the patient has previously had a myocardial infarction.

In any case, ophthalmic beta-blockers are unlikely to interfere with the management of a patient's underlying cardiac condition; they produce plasma levels far lower than the levels necessary to manage cardiovascular disease. (No data is available regarding whether the systemic beta-blockers used to treat CHF have an effect on aqueous production or IOP.)

Debunking Other Myths

Overall, the literature fails to support many of the traditionally accepted beta-blocker negative effects, for example, worsening the symptoms of peripheral vascular disease, such as intermittent claudication, or prolonged hypoglycemia in Type II diabetics.

In some cases, the supportive evidence only involves systemically administered beta-blockers. For example, systemics have been shown to reduce exercise tolerance and exercise work output. (This is not the result of a reduction in heart rate or blood pressure, which ophthalmic doses of a beta-blocker may cause during exercise; complex alterations in energy and electrolyte metabolism are involved.) In contrast, studies of topical beta-blocker administration didn't find any reduction in exercise capacity.

Use of beta-blockers has also been associated with depression, largely because of published case reports and short case series. Nevertheless, the cumulative evidence from prospective placebo-controlled clinical trials, large population-based surveys of patients receiving systemic beta-blocker therapy, and case-controlled studies has overwhelmingly failed to identify such an association. Many of these studies concluded that beta-blockers have no greater risk of causing depression than any other anti-hypertensive agents (which are not associated with depression).

A Resource Worth Using

Clinical evidence does confirm that some patients aren't good candidates for beta-blockers, including those with reactive airways disease, symptomatic bradycardia or newly diagnosed nonphysiologic bradycardia. But beta-blockers are safe for many patients previously thought to be inappropriate candidates.

With the call for more aggressive IOP control, the need for combination drug therapy is inescapable -- even with the advent of the prosta-glandin agents. Let's not unnecessarily deprive patients of a potentially significant therapeutic response.

Dr. Lama is assistant professor of ophthalmology and associate director of the Glaucoma Division at the Institute of Ophthalmology and Visual Science, New Jersey Medical School, and he's trained and board certified in internal medicine. Dr. Lama has no financial interest in any products mentioned.