1197
possibility is that treatment is required for longer than
From cardiac to vascular protection: the next chapter enzyme (ACE) inhibitors introduced in the late 1970s as antihypertensive drugs. Use of these agents was soon extended to the
Angiotensin converting
were
treatment of heart
failure, and subsequently of left ventricular dysfunction. The combination of a diuretic and a converting enzyme inhibitor is now standard treatment for clinical congestive heart failure. Although ACE inhibitors provided significant haemodynamic and symptomatic benefit in heart failure, and also improved the chances of survival, the overall outlook for treated patients remained poor because ventricular dysfunction is usually advanced by the time clinical features of congestion become apparent. Consequently, researchers started to take an interest in a preventive approach to the treatment of left ventricular dysfunction. Better understanding of the process of progressive ventricular dilatation and dysfunction that sometimes follows myocardial infarction, and the prognostic relevance of ventricular volumes, underlined the importance of limiting infarct size after coronary occlusion and of preventing subsequent ventricular dilatation. Infarct artery patency and ventricular loading conditions influence ventricular remodelling, so thrombolysis and ACE inhibition provide a sequential approach to the management of selected patients with myocardial infarction. When experimental and clinical studiesl-4 had shown the potential of ACE inhibition to attenuate ventricular dilatation following myocardial infarction, several large mortality trials were initiated to determine the value of such treatment in terms of heart failure prevention and improved survival. A trio of such studies was published earlier this year,5-7 and a report in this issue (p 1173) takes the story a stage further. CONSENSUS 115 showed a neutral mortality outcome after early administration of enalapril intravenously and then orally; treatment was initiated within 24 h of onset of symptoms of infarction. This result raises the possibility that acute ACE inhibition had some early harmful effects that offset any later benefit of treatment. Early hypotension could compromise coronary perfusion and worsen ongoing ischaemia, and very early inhibition of myocyte and collagen growth achieved by blockade of angiotensin II could increase early infarct expansion.9 Another
the 6 months allowed in the trial for benefit to emerge. The SOLVD prevention trial6 included symptomfree patients with ejection fractions of less than 35%. About 80% had ischaemic heart disease but the preceding myocardial infarction was months before randomisation in many cases. Enalapril treatment significantly reduced the incidence of heart failure and hospital admission, with a trend towards reduced cardiovascular mortality. The SAVE trial7 included patients with definite myocardial infarction and left ventricular dysfunction (ejection fraction
possibility is that treatment is required for longer than
From cardiac to vascular protection: the next chapter enzyme (ACE) inhibitors introduced in the late 1970s as antihypertensive drugs. Use of these agents was soon extended to the
Angiotensin converting
were
treatment of heart
failure, and subsequently of left ventricular dysfunction. The combination of a diuretic and a converting enzyme inhibitor is now standard treatment for clinical congestive heart failure. Although ACE inhibitors provided significant haemodynamic and symptomatic benefit in heart failure, and also improved the chances of survival, the overall outlook for treated patients remained poor because ventricular dysfunction is usually advanced by the time clinical features of congestion become apparent. Consequently, researchers started to take an interest in a preventive approach to the treatment of left ventricular dysfunction. Better understanding of the process of progressive ventricular dilatation and dysfunction that sometimes follows myocardial infarction, and the prognostic relevance of ventricular volumes, underlined the importance of limiting infarct size after coronary occlusion and of preventing subsequent ventricular dilatation. Infarct artery patency and ventricular loading conditions influence ventricular remodelling, so thrombolysis and ACE inhibition provide a sequential approach to the management of selected patients with myocardial infarction. When experimental and clinical studiesl-4 had shown the potential of ACE inhibition to attenuate ventricular dilatation following myocardial infarction, several large mortality trials were initiated to determine the value of such treatment in terms of heart failure prevention and improved survival. A trio of such studies was published earlier this year,5-7 and a report in this issue (p 1173) takes the story a stage further. CONSENSUS 115 showed a neutral mortality outcome after early administration of enalapril intravenously and then orally; treatment was initiated within 24 h of onset of symptoms of infarction. This result raises the possibility that acute ACE inhibition had some early harmful effects that offset any later benefit of treatment. Early hypotension could compromise coronary perfusion and worsen ongoing ischaemia, and very early inhibition of myocyte and collagen growth achieved by blockade of angiotensin II could increase early infarct expansion.9 Another
the 6 months allowed in the trial for benefit to emerge. The SOLVD prevention trial6 included symptomfree patients with ejection fractions of less than 35%. About 80% had ischaemic heart disease but the preceding myocardial infarction was months before randomisation in many cases. Enalapril treatment significantly reduced the incidence of heart failure and hospital admission, with a trend towards reduced cardiovascular mortality. The SAVE trial7 included patients with definite myocardial infarction and left ventricular dysfunction (ejection fraction
