Introduction

This issue addresses the use of angiotensin-converting enzyme (ACE) inhibition in acute myocardial infarction (AMI), and particularly the use of zofenopril, which has been validated in the SMILE (Survival of Myocardial Infarction Long-term Evaluation) study, a large, randomized, placebo-controlled trial in patients within 24 h of the onset of an anterior AMI and not eligible for thrombolytic therapy. Dr Ambrosioni summarizes this data and also the comparison of zofenopril tested against lisinopril, the only ACE inhibitor currently licensed for use early in AMI [as a result of the GISSI-3 (Gruppo Italiano per lo Studio della Streptochinasi nell’infarto Miocardico) study]. Zofenopril was found to be as effective as lisinopril, and possibly with greater safety in the rather slower (5 day) titration regimen tested in the SMILE study. The safety of this regimen is now confirmed in a new study (SMILE-2) which has tested zofenopril in a large population of patients with AMI in any location, who also received thrombolytics. The biology of angiotensin, particularly the newer information on the effects of angiotensin-II (A-II) blockers on the vasculature and on smooth muscle growth, and the differing actions of ACE inhibitors and A-II blockers (ARBs) is reviewed by George Ertl from Würzburg, while Thomas F. Lüscher from Zürich discussed the work of his group on the interplay of A-II, bradykinin and nitric oxide on endothelial function. These two papers underline the sound theoretical and experimental background for these extended actions of angiotensin, and hence the clinical importance of reducing the impact of angiotensin in clinical states with overt or potential left ventricular dysfunction (LVD) such as heart failure or myocardial infarction. The experimental basis for the use of ACE inhibitors in AMI is reviewed by Scott Solomon from the Harvard team of Mark Pfeffer, whose pioneering work demonstrated the benefit of ACE inhibitors in experimental infarction. There has been considerable debate about whether ACE inhibitors should be given early to most patients with infarction, followed by longer term treatment only in those with LVD, or whether the initial treatment should also only be given to the latter group. The recently released preliminary results of the HOPE (Heart Outcomes Prevention Evaluation) suggest that ACE inhibitors are also beneficial in long-term use in high risk patients without LVD or hypertension. This may therefore encourage the practice [tested in ISIS-4 (Fourth International Study of Infarct Survival) and GISSI-3] of using ACE inhibition in a wider group of patients than just those with LVD [as in the SAVE (Survival and Ventricular Enlargement), AIRE (Acute Infarction Ramipril Efficacy) or TRACE (Trandolapril Cardiac Evaluation) studies]. Finally, Edward Frolich, from the Ochsner Medical Foundation in New Orleans reviews the latest information on the importance of LV hypertrophy and reduced LV compliance for the genesis of so-called diastolic heart failure, an increasingly important source of disability, especially in the elderly. ACE inhibition is a particularly effective strategy in reducing LV hypertrophy. At first sight it might appear dangerous, particularly in AMI, to block the action of the sympathetic and renin–angiotensin systems. Harris pointed out many years ago (1) that the activation of these powerful reflexes by baroreceptor sensing of poor LV function, is an inappropriate evolutionary hangover from the days when an inappropriately low blood pressure was a result of bleeding. Reflexes designed to aid survival after accident or trauma are harmful in the setting of LV damage. We older clinicians have been fascinated to witness the development of the widening clinical applications of ACE inhibition over the last three decades.