Beta blocker drugs have now been shown to lengthen the lives of people at risk of sudden death due to irregular heart beats, according to a study published in today's rapid access issue of Circulation: Journal of the American Heart Association.

The protective mechanism of beta blockers is unclear, says lead author Kristin E. Ellison, M.D., of Brown Medical School in Providence, R.I. It is likely due to the combined effects of beta blockers improving blood flow and reducing blood pressure, heart rate, and rhythm disturbances.

Sudden cardiac death occurs when the heart stops abruptly (cardiac arrest). It kills about 250,000 American lives every year, according to the American Heart Association. Most cardiac arrests that lead to sudden death occur when the electrical impulses in a diseased heart become rapid, called ventricular tachycardia, or chaotic, called ventricular fibrillation.

Beta blockers have been shown to reduce the risk of death by 25 percent to 40 percent in patients who've had a recent heart attack and to reduce sudden cardiac death up to 50 percent in patients with a recent heart attack, researchers say. However, until now, it hadn't been known if beta blockers have a similar positive effect on patients three or more years after a heart attack or in a group at high risk for sudden death due to heart rhythm disturbances.

Ellison and colleagues from the Multicenter UnSustained Tachycardia Trial (MUSTT) analyzed data from this prospective, randomized, controlled trial to evaluate the impact of beta blockers on the overall death rate and on death from an arrhythmia (abnormal heartbeat) or the need for resuscitation from cardiac arrest.

MUSTT was designed to test the effectiveness of electrophysiologic (EP) studies -- invasive procedures used to record electrical activity from the heart or to administer medications while monitoring their effects. EP studies can test how well antiarrhythmic therapy reduces sudden death and death from other causes in patients with coronary heart disease. The enrollees had a prior heart attack, an ejection fraction (EF) -- a measure of the heart's pumping strength -- less than or equal to 40 percent, and nonsustained ventricular tachycardia during EP testing. On average, they were enrolled 39 weeks after their most recent heart attack.

The group was divided into those with sustained tachycardia and those without it. The first group was randomly assigned in equal proportions to antiarrhythmic therapy or no therapy, with a small number receiving implantable cardioverter defibrillators (ICDs) if they didn't respond to antiarrhythmic drugs. The group without sustained tachycardia received no antiarrhythmic therapy and was recorded in a registry.

The analysis reviewed 2,096 patients (702 randomized and 1,394 registry patients) enrolled at 85 sites in the United States and Canada between November 1990 and October 1996. Of them, 799 patients received beta blockers -- 314 in the randomized group and 485 in the registry group. Of patients who didn't receive a beta blocker, 388 were in the randomized group and 909 were in the registry.

Researchers found that death rates for beta blocker patients were 16 percent at two years and 34 percent at five years, significantly lower than the death rates of 27 percent at two years and 50 percent at five year for patients not receiving beta blockers.

The life-saving properties of beta blockers were consistent across the spectrum of study patients, such as those with and without inducible tachycardia. Patients with ICDs were the exception.

In contrast to the positive effect that beta blockers had on the overall death rate, the drugs didn't significantly reduce arrhythmic death or cardiac arrest, the study's primary end points. However, the authors note, "there was a trend toward fewer arrhythmic events and improved survival in those treated with antiarrhythmic drugs in combination with beta blocker therapy compared with antiarrhythmic therapy alone."

This trend was not seen in patients with ICDs, likely reflecting the "significant impact of ICD therapy on sudden cardiac death and the difficulty in further decreasing event rates," they add.

The authors note that patients treated with beta blockers were younger, had higher EF rates, higher rates of recent angina, and more recent heart attacks.

A limitation of the study was the inability to randomize the use of beta blockers because the administration of this therapy was left to the discretion of the referring physicians. Another drawback was that the effects of beta blockers in patients who received antiarrhythmic drugs may be obscured because several of these drugs possess some beta blocker activity.

Even so, the significant decrease in the overall death rate of these high-risk patients taking beta blockers and who hadn't had a recent heart attack combined with previous similar evidence lead the authors' to conclude "it is appropriate to prescribe these drugs in patients with the characteristics of those enrolled in the MUSTT trial."

Co-authors are Gail E. Hafley; Kathleen Hickey; Joyce Kellen; James Coromilas, M.D.; Kenneth M. Stein, M.D.; Kerry L. Lee, Ph.D.; and Alfred E. Buxton, M.D., for the MUSTT investigators.

The National Heart, Lung and Blood Institute helped fund the study.

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Circulation: JAHA, 29-Oct-2002 (29-Oct-2002)