Do ACE inhibitors or angiotensin II antagonists reduce total mortality and arrhythmic mortality? A critical review of controlled clinical trials

ACE-inhibitors (ACE-I) represent effective drugs more and more widely used in acute myocardial infarction (AMI) patients, in post AMI patients and mainly, today, in CHF patients. A complete review of the scientific literature and of all the randomized controlled clinical trials (RCTs), where ACE-I have been tested directly or in association with other drugs, have been performed. ACE-I effects on total mortality (TM) and arrhythmic mortality (AM) and other composite clinical endpoints have been evaluated. It is well known that frequent ventricular arrhythmias (VA) and a high incidence of sudden death (SD) can be documented in CHF patients; nevertheless a direct relationship between VA, TM, and AM has not been clearly demonstrated; neither beneficial effects, on the same endpoints, of the treatment and suppression of ambient VA in CHF. Conversely, sometimes clear negative effects on both TM and AM have been observed. According to individual studies and two recent complete and large metanalysis, ACE-I were unable to reduce AM, but they reduced TM. Furthermore, they can affect and modify many, if not all, of the triggering factors of VA and SD in this context. Differently from ACE-I, betablockers (BB) have been clearly associated with a reduction in TM and AM, in the same context. Thus, at present time, ACE-I, with or without BB, should be considered the standard therapy in all patients with CHF, if not contraindicated. Angiotensin II antagonists (All-a) probably represent a comparably effective treatment, in all CHF patients and mainly in those patients, suffering from side effects or showing intolerance to ACE-I, but we are still lacking definitive data from RCTs. In many RCTs, conducted with traditional antiarrhythmic drug therapy (ADT), these drugs have been widely used, contributing probably, in a consistent way, to some of the positive results of these studies. All primary and some secondary implantable defibrillators (ICD) RCTs, in the prevention of SD, have included these drugs as the standard treatment of the underlying cardiac disease, with or without CHF. The same therapeutical strategy is regularly applied in all biventricular pacing (BP) RCTs, with or without the ICD. These trials are supposed to assess the reduction in TM and AM, preventing deterioration or progression of CHF and improving the quality of the patients' s life. Finally, according to these clinical evidences, in the last part of the review, we stress the need for a more widespread implementation of ACE-I and AII-a in treating CHF patients.