TRENTO, ITALY. The goal of the GISSI-AF trial was to determine if addition of the angiotensin II-receptor blocker (ARB) valsartan to established medical therapies would reduce the recurrence of AF in patients with cardiovascular disease. The trial enrolled 1442 patients with documented AF and hypertension (85%) and/or coronary artery disease (12%). The average age of the participants was 68 years, 38% were women, 15% had diabetes, and all were in normal sinus rhythm (NSR) at time of enrolment. All patients were provided with a trans-telephonic monitoring device and underwent clinical examination at 2, 4, 8, 24 and 52 weeks following enrolment.

The researchers observed that patients who had experienced 2 or more episodes in the 6-month period prior to enrolment had a 3-fold increased risk of experiencing two or more episodes during the 1-year follow-up. Patients on amiodarone had a significantly lower risk, while those on diuretics had a significantly higher risk of recurrence. Afibbers with a low resting heart rate also had an increased risk of recurrence. There was a trend for aldosterone blockers (spironolactone, eplerenone) to be protective, but none of the other drugs, including class I antiarrhythmics (propafenone, flecainide, disopyramide), beta-blockers, calcium channel blockers, statins, ACE inhibitors, and ARBs had any significant effect on recurrence rate. The authors suggest the following explanations for their findings:

• A low heart rate may reflect parasympathetic (vagal) predominance which, in turn, could be associated with a higher recurrence rate. NOTE: The association with a low heart rate was still significant after adjusting for the use of beta- and calcium channel blockers.
• The use of diuretics can induce hypokalemia (potassium deficiency), but there was no significant difference in serum potassium levels between patients with recurrence and those without. The researchers suggest that loop diuretics (furosemide – Lasix) may stimulate the renin-angiotensin-aldosterone system and subsequent AF recurrence or, alternatively, they may cause alterations in the ionic channel activities of atrial myocytes.

The Italian researchers suggest their finding that diuretic use is associated with an increased risk of AF recurrence may have important clinical implications in view of the widespread use of these drugs in the treatment of AF patients with hypertension and heart failure.

Disertori, M, et al. Clinical predictors of atrial fibrillation recurrence in the GISSI-AF trial. American Heart Journal, Vol. 159, May 2010, pp. 857-63

Editor's comment: The GISSI-AF study clearly confirms that the use of non-potassium-sparing diuretics [hydrochlorothiazide and furosemide (Lasix)] can be detrimental in AF patients treated for hypertension or heart failure. There is no reason to believe that they would not also be detrimental in lone afibbers. Thus, if one needs diuretic treatment it should preferably include a potassium-sparing diuretic such as amiloride or triamterene. NOTE: Serum potassium levels should be closely monitored if supplementation is used in conjunction with potassium-sparing diuretics.