What have the ACE-inhibitor trials in postmyocardial patients with left ventricular dysfunction taught us?
A series of elegant experimental studies and careful clinical observation over a decade or more have led to the concept of 'infarct expansion' and 'remodelling' of the heart, culminating in a number of major mortality studies indicating the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in patients after myocardial infarction (MI). But has this concept been too narrow in predicting which patients might benefit from treatment with ACE inhibitors? Measurable infarct-expansion with progressive dilatation probably occurs in less than 20% of patients, whereas increase in volume and hypertrophy of the heart as responses to compromised function are likely wherever significant myocardial damage has occurred. Irrespective of infarct expansion, cumulative extensive damage can lead to an inevitable downward spiral with gross ventricular dilatation and death in heart failure. But in the majority of patients after MI a 'new equilibrium' is established in which initial dilatation and subsequently hypertrophy restore adequate function. Is it possible to distinguish patients in whom the cost and inconvenience of long-term therapy with an ACE inhibitor justify the likely benefit from treatment after an MI? The SAVE, AIRE and recent TRACE studies allow a rational approach for the clinician, indicating the effectiveness of these drugs in patients with evidence of impaired ventricular function. However, the prospect that ACE inhibitors prescribed long term might also prevent myocardial reinfarction could justify wider use. Post-MI patients are an easily identifiable high-risk group for a cost-effective programme of secondary prevention. Reinfarction in an already damaged ventricle carries a particularly poor prognosis and its prevention by ACE inhibitors could make a major contribution to the undoubted benefit from these agents. The recently completed TRACE study with its long-term follow-up may help resolve this issue, which is also being investigated in a number of long-term prospective studies in populations at high risk of cardiovascular disease.
Reynolds
G
G
Institute for Cardiovascular Research, Leeds University, UK.
Hall
A S
AS
Ball
S G
SG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D006333:Heart Failure / Q000517:prevention & control*; D006801:Humans; D009203:Myocardial Infarction / Q000401:mortality*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors