Aldosterone Blockade in Heart Failure
Aldosterone Blockade in Heart Failure
In spite of treatment with inhibitors of the renin-angiotensin system, plasma levels of aldosterone increase progressively in heart failure. This phenomenon of aldosterone escape is associated with adverse outcome. The aldosterone receptor antagonists spironolactone and eplerenone can improve prognosis for patients with heart failure. The commonest, and often problematic unwanted effect of these agents, hyperkalaemia, may limit their usefulness and brings with it the need for careful clinical and biochemical monitoring. Recent trials, however, have shown clear benefits for large groups of patients for spironolactone (in severe chronic heart failure) and eplerenone (heart failure soon after acute myocardial infarction). Due consideration should be given to the addition of the appropriate aldosterone antagonist in suitable patients.
A number of statements are often made regarding chronic heart failure. These include: this is the only cardiovascular disease to be increasing in prevalence; heart failure accounts for 5% of all unplanned, adult hospitalisations in the UK; and the number of primary care consultations and secondary care episodes ascribable to heart failure will rise markedly over the next two decades. These facts merit careful consideration, for they are a true representation of the burden of disease associated with this condition.
It is pertinent to this discussion to remind ourselves that the commonest cause of heart failure is coronary heart disease and it is in the coronary care unit that the patient with heart failure secondary to acute myocardial infarction (AMI) presents. The presence of clinical or radiological signs of heart failure in a patient following AMI remains one of the strongest predictors of adverse outcome. Even in the current era of sophisticated risk assessment using neurohormonal markers and a variety of imaging modalities, the severity of heart failure as assessed by simple clinical parameters in the immediate post-AMI period carries powerful prognostic information.
In heart failure after AMI, the physician is dealing primarily with left ventricular systolic dysfunction (LVSD). Pharmacotherapy for LVSD following AMI has advanced considerably in recent years. Emphasis is now placed on early introduction of drugs shown in clinical trials to maintain quality of life, retard disease progression, and delay death. Indeed the management of heart failure is supported by as good an evidence-base as exists in cardiovascular medicine. Why then does the search for new treatments continue? Put simply, in spite of the efficacy of modern treatments, the prognosis for patients with LVSD following AMI remains poor. Figure 1 illustrates the point. This shows survival curves for patients after AMI stratified by Killip class (a measure of the degree of heart failure present on clinical examination) during admission. It is clear that LVSD has a marked impact on prognosis, in spite of these individuals being managed according to current guidelines with aspirin, statins, angiotensin-converting enzyme (ACE) inhibition and beta blockade.
(Enlarge Image)
Survival curves for patients with left ventricular systolic dysfunction after acute myocardial infarction stratified by Killip Class
In spite of treatment with inhibitors of the renin-angiotensin system, plasma levels of aldosterone increase progressively in heart failure. This phenomenon of aldosterone escape is associated with adverse outcome. The aldosterone receptor antagonists spironolactone and eplerenone can improve prognosis for patients with heart failure. The commonest, and often problematic unwanted effect of these agents, hyperkalaemia, may limit their usefulness and brings with it the need for careful clinical and biochemical monitoring. Recent trials, however, have shown clear benefits for large groups of patients for spironolactone (in severe chronic heart failure) and eplerenone (heart failure soon after acute myocardial infarction). Due consideration should be given to the addition of the appropriate aldosterone antagonist in suitable patients.
A number of statements are often made regarding chronic heart failure. These include: this is the only cardiovascular disease to be increasing in prevalence; heart failure accounts for 5% of all unplanned, adult hospitalisations in the UK; and the number of primary care consultations and secondary care episodes ascribable to heart failure will rise markedly over the next two decades. These facts merit careful consideration, for they are a true representation of the burden of disease associated with this condition.
It is pertinent to this discussion to remind ourselves that the commonest cause of heart failure is coronary heart disease and it is in the coronary care unit that the patient with heart failure secondary to acute myocardial infarction (AMI) presents. The presence of clinical or radiological signs of heart failure in a patient following AMI remains one of the strongest predictors of adverse outcome. Even in the current era of sophisticated risk assessment using neurohormonal markers and a variety of imaging modalities, the severity of heart failure as assessed by simple clinical parameters in the immediate post-AMI period carries powerful prognostic information.
In heart failure after AMI, the physician is dealing primarily with left ventricular systolic dysfunction (LVSD). Pharmacotherapy for LVSD following AMI has advanced considerably in recent years. Emphasis is now placed on early introduction of drugs shown in clinical trials to maintain quality of life, retard disease progression, and delay death. Indeed the management of heart failure is supported by as good an evidence-base as exists in cardiovascular medicine. Why then does the search for new treatments continue? Put simply, in spite of the efficacy of modern treatments, the prognosis for patients with LVSD following AMI remains poor. Figure 1 illustrates the point. This shows survival curves for patients after AMI stratified by Killip class (a measure of the degree of heart failure present on clinical examination) during admission. It is clear that LVSD has a marked impact on prognosis, in spite of these individuals being managed according to current guidelines with aspirin, statins, angiotensin-converting enzyme (ACE) inhibition and beta blockade.
(Enlarge Image)
Survival curves for patients with left ventricular systolic dysfunction after acute myocardial infarction stratified by Killip Class