Which patients with impaired ventricles should receive an ACE inhibitor?

Which patients with impaired ventricles should receive an ACE inhibitor? What are the survival advantages? Do AT1-receptor antagonists confer the same advantages?

Not all impaired left ventricular (LV) function is an indication for ACE-inhibitor treatment. Specifically, left ventricular hypertrophy due to hypertension or aortic stenosis may be associated with diastolic dysfunction, yet ACE inhibition is only one of several therapies that will regress LV hypertrophy, even though some believe that for this purpose it is one of the best. Similarly, the defects of ventricular function seen in hypertrophic cardiomyopathy are not a clear indication for ACE inhibition.

The following patients should be treated with an ACE inhibitor

Symptomatic patients
All patients with clinically diagnosed heart failure should receive an ACE inhibitor. The survival advantages are consistent (mortality reduction of about 20%) and far outweigh the relatively small risk of serious side effects. In post-infarct clinically diagnosed heart failure, ACE inhibition reduced mortality by 27% at an average follow up of 15 months, and 36% with a mean follow up of nearly 5 years.

Post-infarct patients without overt heart failure but with impaired left ventricular systolic function
These patients should receive an ACE inhibitor. This will give them benefit even in the absence of symptoms, as shown in the SOLVD prevention trial.2 Most patients were post-infarct, and most were New York Heart Association (NYHA) class 1, despite the low ejection fraction of 35% or less.

Benefit to risk ratios
In the SAVE study3 of post-infarct patients with an ejection fraction of 40%, the chief treatment-related adverse effects of captopril were cough, taste abnormally, dizziness or hypotension. Calculations suggest that a reduction in mortality could be achieved without side effects after treating only 24 patients.4 Yet nearly 200 patients would have to be treated before encountering one case in which side effects were found without a mortality benefit. This makes ACE inhibition a very safe form of therapy.

Do AT1-receptor blockers confer the same advantages?
These agents are not currently (1999) licenced for use in heart failure in the USA nor in the UK. There are some key theoretical differences from ACE inhibitors, such as decreased breakdown of the protective vasodilator bradykinin during ACE inhibition, versus the likelihood that AT1 blockade gives more complete inhibition of the renin-angiotensin system than does ACE inhibition. The ELITE II trial showed losartan to be no more effective than captopril in reducing mortality in the elderly. In the subgroup of patients taking beta blockers, mortality decreased in those taking captopril, compared with losartan. ACE inhibitors, therefore, remain the cornerstone of the therapy of heart failure.

It should be noted that data support the use of spironolactone administration (25mg/day) in those with severe heart failure. Concerns about hyperkalaemia relating to concomitant use with ACE inhibition were generally unfounded in this study, although potassium levels in the order of 6mmol/l were accepted.