Beta-blockers are not so bad after all

Study shows one drug reduces death by 34%

Contrary to conventional wisdom, certain beta-blockers actually ease the symptoms of patients in heart failure.

Rather than worsening patients’ conditions, these medications helped reduce the need for hospitalization — and in a number of cases — extended lives.

A new international study, which specifically involved the beta-blocker metoprolol, followed 3,991 heart failure patients in the United States and thirteen European countries for one year. In June, researchers reported that the drug reduced deaths by 34%. Those findings sharply contradicted the longstanding belief that, because they slow down the heart rate, beta-blockers, in general, should be judiciously avoided in treating heart failure.

As a result of the study’s findings as well as those of similar studies, the American Heart Association plans to update its treatment guidelines to include recommendation of beta-blockers’ use for most heart failure patients, says Sharon Hunt, MD, a Stanford University cardiologist in Palo Alto, CA, and chairwoman of the updating committee.

Sidney Goldstein, MD, co-author of the study and a cardiologist at Henry Ford Hospital in Detroit, has long been a proponent of beta-blockers’ use in treating heart failure. He was the principal investigator in the Beta Blocker Heart Attack Trials, published in the Journal of the American Medical Association in the early 1980s.

"What’s most significant is that it illustrates the major impact metoprolol has in treating sudden death, which represents about two-thirds of the mortality rate of heart failure patients," Goldstein says. From that standpoint, the drug is superior to ACE inhibitors, mainstays in heart failure treatment, which, although successful in reducing symptoms, do little in terms of modifying the sudden death rate, he adds.

Hospitalizations reduced by one-third

The study was funded by Wilmington, DE-based Astra Zeneca, manufacturers of metoprolol, which is sold in the United States under the name Toprol XL. The study was led by Ake Hjalmarson, MD, of Sahlgrenska University Hospital in Gothanburg, Sweden. Of the patients followed, all were given conventional medication. Metoprolol, in an ex-tended-release form, was administered to about a half, and the rest received a placebo.

Along with a significant reduction in the number of deaths, there were about a third fewer hospitalizations in the beta-blocker group. In addition, symptoms improved in 28% of the group treated with beta-blockers, compared with 25.8% of the placebo group, and 50% of the beta-blocker group reported feeling better.

"Twenty years ago, the common wisdom was that beta-blockers were the worst thing you could possibly use in a failing heart. Now, rather than being looked at as last-ditch, experimental, or cutting-edge therapy, they’re considered a standard, routine treatment that should be used in most cases of heart failure," says Robert E. Safford, MD, professor of medicine and chairman of internal medicine at Mayo Clinic in Jacksonville, FL.

One reason acceptance of the drugs in the United States has been slow in coming is that, initially, they were available only in doses that were too strong for heart failure patients just beginning to take the drug to tolerate, he says. Even though they were directed to break the pills into quarters, "Unless a pill is scored, when you try to break it, it turns to dust. So first, pharmaceuticals had to develop a pill with a dosage low enough to be tolerated by people in heart failure," Safford says.

Slowing down the revs’

But the primary reason for their belated endorsement was the concern that beta-blockers would reduce the heart rate to a level so low that it could prove fatal for patients who already were in a debilitated condition.

"Looking at the heart as a pump, the thinking was, If you slow it down, it’s going to pump even less effectively.’ But, as it turns out, sometimes the heart [can] get in trouble from overstimulation. If, for example, it’s beating at 120-130 beats per minute, sometimes, to use the analogy of a automobile engine, it is better to put a rev’ limit on it, of 90-100 beats per minute," says Charles Inman Wilmer, MD. Wilmer is director of angioplasty, cardiac disease specialist, and director of data management at the Fuqua Heart Center of Piedmont Hospital in Atlanta.

There are, of course, patients for whom beta-blocker therapy is too risky — such as those with a tendency to wheeze, or those with severe bronchospasms or asthma, he says.

"Patients with the fastest heart rate may have the worst cardiomyopathy and therefore be unable to tolerate them. In addition, those with the most severe heart failure, either because their heart doesn’t squeeze well or their blood pressure is too low, cannot tolerate them. . . . More likely are patients with mild to moderate heart failure, and those who are more tachycardic," Wilmer explains.

"If their blood pressure [has] fallen, they’ll need to decrease their dosages of diuretics or ACE inhibitors," says Safford, adding that as the beta-blocker dosage is gradually increased over several months, with adjustments every couple of weeks, close contact with the physician should be maintained.

As it takes a while for the drug to begin taking effect, he cautions against delaying beta-blocker therapy until the last possible minute. "Since it does take some time to show improvement, [that therapy] needs to be added early on, and not late, as a last-ditch effort," he points out.

Safford has treated patients who have experienced significant improvement in pump function, from "dramatically reduced, to mildly or moderately reduced. On an average, their symptoms improve — and, in many cases, the progression of the disease is attenuated. At the very least, I think, the patient can expect his pump function to stabilize."

As far as side effects, "Most patients should be prepared to experience quite a bit of fatigue. Generally, that can last for a couple of weeks, on up to several months. . . . As reduced blood pressure is one of the side effects, they will at some point need to decrease their diuretics or ACE inhibitors, especially if their blood pressure has fallen," Safford says.