Two drugs are better than one to prevent return of atrial fibrillation

The high blood pressure drug irbesartan delayed the recurrence of irregular heartbeats, researchers report for first time in today’s rapid access issue of Circulation: Journal of the American Heart Association.

The drug helped stop irregular heartbeats (arrhythmias) known as atrial fibrillation (AF). AF is a disorder in which the two small, upper chambers of the heart quiver instead of beating effectively. Blood that isn’t pumped out may pool and clot. If a piece of clot leaves the heart and lodges in an artery to the brain, a stroke results.

Irbesartan is in a class of drugs called angiotensin II antagonists, or blockers. They are used to treat several cardiovascular disorders such as high blood pressure and heart failure.

AF is considered the most common sustained heart arrhythmia, and its incidence rises with age to about 10 percent in people over age 75, says study author Concepción Moro, M.D., professor of medicine at the University of Alcala and director of the arrhythmia unit at the Ramon y Cajal hospital in Madrid, Spain.

“AF is believed to double the risk of death and quadruple the risk of strokes,” she says. “In addition, AF may accompany many cardiac conditions such as valvular heart disease, cardiomyopathies and ischemic heart disease. It can also appear along with high blood pressure and other systemic diseases such as hyperthyroidism, although in many patients the cause is unknown.”

AF is typically treated with antiarrhythmic drugs such as amiodarone, anti-clotting agents, and electrical cardioversion, a procedure that uses an electrical impulse to destroy areas of heart tissue where the rhythm disturbances originate. However, AF often recurs despite these treatments, so new options are needed, Moro says.

“The clue for this work was evidence that patients treated with angiotensin II antagonists for other conditions developed fewer atrial arrhythmias than expected,” she explains.

In the study, 154 patients who had continuous AF for more than seven days were randomly assigned into two groups to receive one of two treatments. Group I got amiodarone, while group II received amiodarone plus irbesartan. All of the patients were scheduled to have electrical cardioversion three weeks after beginning therapy.

At the three-week point, 62 patients had stable heart rhythms on medication alone and 92 went on to have electrical cardioversion, 83 of them successfully. During the next two months, 26 patients had a recurrence of AF. An analysis found the two-month probability of maintaining a stable heartbeat was nearly 85 percent for subjects who got irbesartan compared to 63 percent for those who did not.

“Our analysis revealed that using the angiotensin II receptor antagonist was the only significant variable related to maintaining heart rhythm after cardioversion,” the researchers write.

Patients treated with irbesartan had a greater probability of remaining free of AF than those treated with amiodarone alone (80 percent vs. 56 percent). One of the most important factors to predict recurrence was the duration of AF before randomization.

“There were a very low number of adverse events, well within the expected limits, and the incidence rate was similar in both groups,” Moro notes.

One 51-year-old man in group II suffered sudden death three weeks after his successful cardioversion procedure, but his death was not believed to be related to the procedure because of the time lag, she says. In addition, three patients in group I and two in group II had adverse events that required therapy to be discontinued.

Lead author of the study was Antonio Hernandez-Madrid, M.D. Other co-authors were Manuel G. Bueno, M.D.; Jose M.G. Rebollo, M.D.; Irene Marín, M.D.; Gonzalo Peña, M.D.; Enrique Bernal, M.D.; Aníbal Rodriguez, M.D.; Lucas Cano, M.D.; José M. Cano, M.D.; and Pedro Cabeza, M.D.

This work was supported in part by a grant from the Ministry of Health of Spain and by a grant from the drug company Sanofi-Synthelabo.

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