The 1-year rate of recurrence of AF in the GISSI-AF population was nearly 52% irrespective of the underlying CV disorder and the baseline characteristics of patients.

Valsartan (up to 320 mg/daily) on top of recommended treatments for the arrhythmia and the underlying CV disorders (including ACE-inhibitors) did not reduce the rate of recurrence of AF. The effect of valsartan was similar in all predefined subgroups of patients, with the exception of those with HF/LVD for whom a beneficial effect (not significant) was observed. The safety and tolerability profile of valsartan (up to 320 mg) was confirmed to be satisfactory.

GISSI-AF is the largest prospective RCT ever conducted testing renin-angiotensin-aldosterone-system (RAAS) blockers in patients with AF adequately powered.

Differently from post-hoc or secondary analyses of other trials, the occurrence of AF was specifically evaluated through periodical ECG and transtelephonic monitoring.

A possible reason why valsartan was not effective in reducing AF re-occurrence is that the blockers of the RAAS are more effective when the RAAS is highly activated, while patients enrolled in GISSI-AF, due to their relatively low-risk clinical conditions and to the optimization of background therapy, had likely a low level of RAAS activation.

The trend towards a beneficial effect of valsartan in patients with HF/LVD may confirm this hypothesis.