Studies Challenge Thinking on Irregular Heart Rhythm

By LAWRENCE K. ALTMAN

wo new large international studies being reported today are likely to upset medical dogma for treating atrial fibrillation, a common irregularity of the heartbeat that can lead to debilitating strokes and other life-threatening complications.

The studies, conducted independently, came to similar surprising findings and promise to change treatment for millions of people with the condition, including more than two million Americans.

But health officials, leading cardiologists and the authors of the studies, which were conducted in the United States, Canada and the Netherlands, warned patients not to change their therapy for atrial fibrillation without consulting their doctors.

Less costly and safer drugs that adjust the heart's rate are as effective as other drugs and procedures that control the heart's rhythm, according to the findings being reported in The New England Journal of Medicine. The rate therapy also led to fewer admissions to a hospital in the studies, presumably because of more side effects from the drugs used to try to restore normal heart rhythm.

A complex electrical system controls each heartbeat. It starts with a charge in an atrium, an upper chamber of the heart, that passes through nerve fibers to the ventricles, the lower chambers, to produce a regular rhythm. The rate, or speed, varies with physical activity, emotions and stress.

In atrial fibrillation, the heart beats irregularly because the atria fire electrical signals in an uncontrolled and very fast way. When the signals arrive in the ventricles in an erratic pattern, the ventricles pump blood less efficiently to the body. The slower flow of blood promotes formation of clots in the atria.

Atrial fibrillation is the most common persistent heart rhythm irregularity. It can produce symptoms like palpitations, dizziness and breathlessness, particularly on walking and physical exertion.

The condition usually results from heart attacks, heart failure, high blood pressure, damage to heart valves, diabetes, an overactive thryoid gland and excessive alcohol consumption. Sometimes atrial fibrillation occurs without any apparent underlying cause.

The incidence of atrial fibrillation increases with age to the point where it affects about 6 percent of those over age 80. Atrial fibrillation is a growing health problem worldwide because of the growing number of elderly people in this country and elsewhere.

Most American doctors have preferred a treatment strategy to restore a normal heart rhythm on the presumption that it lowers the incidence of complications like strokes and side effects from drugs, improves cognitive function and improves the quality of life.

The strategy of restoring a normal rhythm was a largely uncontested therapeutic goal and was based on intuition, not scientifically based studies. Until now, only two studies, reported a few years ago, compared rate and rhythm strategies, and they were small and the findings inconclusive, said Dr. Robert O. Bonow, the president of the American Heart Association and chief cardiologist at Northwestern University Medical School in Chicago.

But the new studies still leave many unanswered questions, like how applicable the findings are to patients younger than the mostly elderly people who comprised most of the patients in the studies. The studies also underscore the need to develop better drugs and therapies, particularly for patients who have symptoms despite use of drugs to control their heart rates.

How much practice will change will depend as much on patients and physicians.

"We see many patients who have atrial fibrillation who push us to convert their rhythm to normal, thinking that it will be better for them, and we tend to go along with it," said Dr. Valentin Fuster, the chief of cardiology at Mt. Sinai Medical Center in Manhattan.

The studies also reinforced the importance of prescribing and carefully monitoring anti-coagulant drugs to reduce the chances of the formation of blood clots in either treatment strategy. In the studies, strokes tended to occur among those not taking anti-coagulant drugs like warfarin, widely known by the brand name Coumadin, or taking them in inadequate amounts.

Atrial fibrillation promotes the formation of blood clots. The danger comes from pieces of clot that break off to lodge in arteries in the brain, causing strokes, or elsewhere in the body to damage organs. Anti-coagulant drugs showed benefit in the studies even if the atrial fibrillation rhythm returned to normal. The studies will change practice in two ways — "less aggressive in one way and more aggressive in another way," said Dr. Fuster, who is the president-elect of the World Heart Federation.

"The medical community will probably become much more conservative in terms of using a less-aggressive approach" in treating atrial fibrillation, Dr. Fuster said. "On the other hand, the medical community will probably be much more aggressive in" prescribing anti-coagulant drugs, often erroneously referred to as blood-thinners.

The drugs most commonly used to restore a normal rhythm include amiodarone (Cordarone); sotalol (Betapace); propafenone (Rythmol); procainamide; quinidine; flecainide (Tambocor); disopyramide; moricizine; and dofetilide (Tikosyn).

A smaller group of doctors, many in Europe, have favored a less-aggressive strategy — controlling the rate and allowing the atria to continue to fibrillate — even though the strategy was conceptually less appealing than rhythm control. These doctors prescribed digitalis and members of the class of drugs known as beta blockers and calcium channel blockers.

So when American and European experts issued guidelines on treating atrial fibrillation, they deferred a recommendation on the strategy until scientific information became available through trials like the ones being reported now, said Dr. Fuster, who headed the guidelines committee.

Dr. D. George Wyse, a professor of cardiology at the University of Calgary, was chairman of the steering committee of the North American study. It involved 4,060 patients at 213 hospitals in the United States and Canada, began in 1995 and was paid for by the National Heart, Lung and Blood Institute, a federal agency in Bethesda, Md. The second involved 522 patients at 31 hospitals in the Netherlands and was paid for by a health care insurance center, a Dutch university cardiology center and a grant from a drug company, 3M Pharma of the Netherlands.

Researchers in the North American study followed patients for an average of 3.5 years and a maximum of 6 years, until Oct. 31, 2001. All had atrial fibrillation and at least one other risk factor for stroke or death. The factors included age, being 65 or older; high blood pressure; diabetes; and heart failure.

One group of 2,027 patients received rate control drugs. The other group of 2,033 patients received rhythm control drugs. Both groups received warfarin.

If drugs failed or patients could not tolerate them, doctors used cardioversion, radiofrequency, surgery or combinations to try to ablate the abnormal rhythm.

When the study ended, 356 patients in the rhythm control group had died from all causes, compared to 310 in the rate control group. During the study, 1,374 patients in the rhythm group were admitted to a hospital, compared to 1,220 in the rate control group. Adverse drug effects like an abnormally slow heart rate and lung problems were more common in the rhythm control group than the rate control group.

Dr. Isabelle C. Van Gelder of the University Hospital in Groningen led the Dutch study that began in June 1998 and ended in July 2001. After a mean of 2.3 years, 39 percent of the 266 patients in the rhythm control group had normal rhythm, compared to 10 percent of the 256 patients in the rhythm control group.

Sixty participants, or 22.6 percent, in the rhythm control group died from all heart-related causes, compared to 44 patients, or 17.2 percent, in the rate control group.

In an editorial in the same issue of the journal, Dr. Rodney H. Falk of Boston University wrote that in treating a first episode of atrial fibrillation "an attempt to restore sinus rhythm is appropriate, although it can no longer be deemed imperative."