Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure

doi:10.1016/S1071-9164(96)80009-1

Journal of Cardiac Failure

Volume 2, Issue 1, March 1996, Pages 47-54

https://doi.org/10.1016/S1071-9164(96)80009-1 Get rights and content

Abstract

In chronic heart failure, angiotensin-converting enzyme inhibitors produce an acute decrease in aldosterone levels. Long-term angiotensin-converting enzyme inhibition is, however, associated with aldosterone suppression that is weak, variable, and unsustained (ie, aldosterone escapes). The possible harmful effects of this residual aldosterone are multiple. Magnesium loss caused by aldosterone and by diuretics could contribute to coronary artery spasm and arrhythmias. Aldosterone blocks norepinephrine uptake by the myocardium; extracellular catecholamines may, therefore, lead to arrhythmias and ischemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a detrimental effect on parasympathetic and baroreflex function. Both angiotensin II and aldosterone stimulate myocardial fibrosis, which may lead to a higher incidence of malignant ventricular arrhythmias. Spironolactone therapy added to the regimen of an angiotensin-converting enzyme inhibitor and diuretic has been shown to cause natriuresis, magnesium retention, increased myocardial norepinephrine uptake, and reduced incidence of ventricular arrhythmias. It may well be that residual aldosterone mediates many harmful effects in chronic heart failure and that to optimize the benefit of blocking the renin-angiotensin-aldosterone system may require specific blockade of residual aldosterone as well as traditional angiotensin-converting enzyme inhibition.

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Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF.
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A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality—a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables—the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73).
A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients.
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Citation Excerpt :
Although blockade of the RAAS traditionally has been performed with ACE inhibitors or ARBs, and more recently direct renin inhibitors have been tried,93 30% to 50% of patients on long-term therapy have unexpected increases of serum aldosterone levels, a phenomenon termed aldosterone breakthrough.93–96 This paradoxic increase in aldosterone levels leads to progression of cardiac and renal disease because ACE inhibitors and ARBs may not adequately block the MR component.92,97–99 The phenomenon of aldosterone breakthrough has been known for some time, is well described in the cardiac literature,97,100 and may explain the mortality benefit of aldosterone blockade as add-on therapy to ACE inhibitors or ARBs in congestive heart failure (CHF).4,5,101
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ReviewAldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure

Abstract

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am Heart J

Am Heart J

Am Heart J

Life Sci

Am J Cardiol

Lancet

Lancet

Life Sci

A placebo controlled trial of captopril in fractory chronic congestive heart failure

J Am Coll Cardiol

Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones and metabolic state

Br Heart J

Captopril in heart failure: a double blind controlled trial

Br Heart J

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure

N Engl J Med

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure

N Engl J Med

Effects of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions

N Engl J Med

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survivaland Ventricular Enlargement Trial

N Engl J Med

Rise in plasma concentrations of aldosterone during long term angiotensin II suppression

J Endocrinol

Evidence of partial escape of RAA blockade in patients with acute MI treated with ACE inhibitors

J Clin Pharmacol

“Escape” of aldosterone production in patients with left ventricular dysfunction treated with an ACE inhibitor: implications for therapy

Cardiovasc Drugs Ther

The chymase-angiotensin system in humans

J Hypertension

Partial escape of ACE inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response

Hypertension

Progression of LV dysfunction during enalapril therapy: relationship with neurohormonal reactivation

Circulation

Progression of LV dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during longterm therapy with ACE inhibitor

Am J Cardiol

ACE inhibition does not suppress plasma All increase during exercise in humans

J Cardiovasc Pharmacol

Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention

Am J Nephrol

Combined spironolactone and converting enzyme inhibitor therapy for refractory heart failure

Aust N Z J Med

Review
Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure