< International Circulation>:  You had a wonderful and interesting presentation.  RAS activation is one of the most important mechanisms hypertension and is also related to the incidence of atrial fibrillation. What do you think about the effects of ACE inhibitors and ARBs for the treatment and prevention of atrial fibrillation?

    Prof. Schneider:  We have found in our meta-analysis that using either an ACE inhibitor or an angiotensin receptor blocker can prevent the development of atrial fibrillation by 33%.  This is when you take all of the studies that have been published together.  This means looking at both primary prevention， the new onset of atrial fibrillation， and also secondary prevention， meaning the recurrence of atrial fibrillation.  In the primary prevention group we have three categories; patients who had hypertension， paitents who had myocardial infarction， and patients who had heart failure.  In the secondary prevention trials we had a group of patients who had had cardioversion for mostly permanent atrial fibrillation and we had a group who had had medical therapy for paroxysmal atrial fibrillation.  Overall there was a reduction in atrial fibrillation by 33%， but there was substantial heterogeneity between trials meaning that the effects comparing individual trials was very inconsistent and that is why we have compared trials more closely in these subgroups.  In hypertension overall there was no effect in the whole group of hypertensive studies.  We included a total of 6 trials in this group， but the trials were very different.  The most striking difference was that the more recent trials used a more sensitive way of detecting atrial fibrillation by using ECG every year and analyzed in a central protocol.  The contrasts with the older trials like the Captoprel Prevention Project and STOP-2 in that they recorded atrial fibrillation only as an adverse event.  Looking at these 6 trials， only the two trials who used yearly ECG recordings found a positive effect of using RAS blockade， which might indicate that you need a better way of detecting atrial fibrillation， especially in this group who has a low rate of developing atrial fibrillation.  Also， in the LIFE trial， patients were included who also simultaneously had hypertension and left ventricle hypertrophy.  Patients who had left ventricle hypertrophy perhaps have the greatest benefit of RAS blockade.

     In the other group of primary prevention who had the most benefit was the group of patients with heart failure.  We have three studies with patients with heart failure and all three show a beneficial effects of RAS blockade， especially the SOLF study， a very old study， that showed a rather large benefit of RAS blockade， and these were the patients who had the most severe left ventricle function.