Heart rhythm drug also helps some failing hearts

March 11, 2001

DALLAS, March 13 - Individuals with heart failure may have another drug treatment option, according to a report in today's Circulation: Journal of the American Heart Association.

The drug, dofetilide, is a class III antiarrhythmic drug normally used to treat tachyarrhythmia, a condition that causes the heart to beat so fast that it can't pump blood effectively. However, class III antiarrhythmia drugs have had mixed effects on treatment of the irregular heartbeats. The drugs have sometimes resulted in an increased occurrence of irregular heartbeats or arrhythmias.

"Patients with congestive heart failure (CHF) have an extremely poor prognosis and a high risk of sudden cardiac death," says lead researcher Bente Brendorp, M.D. Many of these patients might benefit from preventative treatment with an antiarrhythmic drug. However, because of uncertainty about the benefits of using dofetilide and other class III antiarrhythmic medications in treating CHF and other cardiac diseases, cardiologists have been cautious about using them in some heart patients.

In this study, researchers were able to identify a prognostic marker - the QT interval - that can be used to determine which patients can benefit from the drug. The QT interval is a measurement of a waveform on the electrocardiogram (EKG). The EKG is used to measure the heart's electrical activity and diagnose abnormalities in heart rhythm.

"In patients with moderate to severe CHF, those with a baseline QT interval within normal limits had a lower risk of death when treated with dofetilide compared to placebo-treated patients." Brendorp says. "Prolonged QT interval is a cause for caution when using antiarrhythmic drugs because the drug could further prolong the QT interval and cause a deadly arrhythmia," says Brendorp, a clinical researcher in cardiology at Copenhagen University Hospital in Gentofte, Denmark. "However, if our results are confirmed by further tests, this could mean a new line of treatment and improved survival rates in CHF patients who have normal QT intervals."

In a study of 703 individuals with CHF, researchers compared people with short and long QT intervals who were receiving dofetilide or a placebo. Those in the study with shortest QT intervals who received the drug had the lower all-cause mortality than those receiving a placebo.

Congestive heart failure is the inability of a damaged or overworked heart to pump all the blood that returns to it. The result is a back-up of blood in the veins leading to the heart and often a build up of fluids in various parts of the body.

CHF has several underlying causes, including damage from a heart attack, high blood pressure, and an infection of the heart muscle or valves. The life-threatening ailment strikes about 550,000 Americans each year. Survival after CHF diagnosis is about 1.7 years in men and 3.2 years in women.

In this study, 301 individuals received dofetilide and 402 were given a placebo. All had reduced pumping power in their left ventricle, the heart chamber that feeds blood to the rest of the body. They were tracked for an average of 18 months, with a minimum follow-up of one year. The men and women ranged in age from 49 to 84.

During follow-up, 285 (41 percent) of the patients in Brendorp's study died. The death rate was similar between the two groups: 42 percent in the placebo group and 39 percent in the drug-treated patients. However, after the researchers divided the patients into four groups, ranked according to the length of their QT intervals, they found a significant difference.

The people in Brendorp's study had participated in a larger study called the Danish Investigations of Arrhythmia and Mortality on Dofetilide-Congestive Heart Failure (DIAMOND-CHF). This 1,518-patient, randomized, double-blind trial at 34 Danish hospitals sought to determine dofetilide's effectiveness in treating moderate to severe CHF. Half received dofetilide and half a placebo.

The DIAMOND-CHF study produced neutral survival findings - death rates were no different among drug-treated patients compared to those on placebo.

"Our study raises the intriguing question of whether other studies that have had neutral or negative results regarding preventative use of class III antiarrhythmic drugs in high-risk CHF patients, could have had different outcomes had the patients been grouped according to QT intervals," the researchers write.

"If our results hold true in a separate clinical trial, mortality in some patients with CHF can be markedly reduced with the prescription of dofetilide, and perhaps other antiarrhythmic drugs of the same class," Brendorp says.
-end-
Co-authors are Hanne Elming, M.D., Ph.D.; Li Jun, M.D.; Lars Køber, M.D., D.M.Sc.; Marek Malik, M.D., Ph.D., D.M.Sc.; Gorm Boje Jensen, M.D., D.M.Sc.; and Christian Torp-Pedersen, M.D., D.M.Sc.CONTACT:
For journal copies only,
please call: 214-706-1396

For other information, call:
Carole Bullock: 214-706-1279 caroleb@heart.org
Bridgette McNeill: 214-706-1135


American Heart Association

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