Inspra (Pfizer)
25 mg and 50 mg tablets
Approved indication: heart failure post-myocardial infarction
Australian Medicines Handbook section 6.4.2
Low doses of spironolactone have a role in regimens for the treatment of severe heart failure. The beneficial effects of spironolactone are probably related to its antagonism of aldosterone. As aldosterone concentrations are increased in heart failure, it is a target for drug therapy.
Like spironolactone, eplerenone is a potassium-sparing diuretic. It blocks the attachment of aldosterone to its receptor. As this can reduce blood pressure, eplerenone has been approved as an antihypertensive drug in the USA.
In a study of patients with hypertension and left ventricular hypertrophy eplerenone was found to reduce left ventricular mass, particularly if it was combined with enalapril.1 If eplerenone can prevent ventricular remodelling it may be beneficial after acute myocardial infarction.
A multinational clinical trial enrolled several thousand patients with left ventricular dysfunction and heart failure 3-14 days after a myocardial infarction. In addition to standard therapy (excluding spironolactone), 3319 patients were assigned to take eplerenone while 3313 patients took a placebo. The dose of eplerenone was 25 mg daily increasing to 50 mg daily after four weeks. After follow-up for an average of 16 months, 478 of the patients taking eplerenone had died compared with 554 of the placebo group. This was a 15% reduction in relative risk. Most of the deaths were from cardiovascular causes, particularly sudden death.2
Patients taking eplerenone are at risk of hyperkalaemia. In the heart failure trial serious hyperkalaemia (6.0 mmol/L) occurred in 5.5% of patients compared with 3.9% of the placebo group.2 Apart from hyperkalaemia, other reasons for discontinuing eplerenone include dizziness and altered renal function.
Eplerenone is mainly metabolised by the liver with most of the metabolites being excreted in the urine. The drug is contraindicated in patients with moderate to severe renal impairment. As it is metabolised by cytochrome P450 3A4 it should not be prescribed with drugs, such as ketoconazole, that inhibit this enzyme.
As eplerenone is said to have relative selectivity for mineralocorticoid receptors, it may not have as many adverse effects as spironolactone. However, gynaecomastia and breast pain can still occur. Although the trials cannot be directly compared, spironolactone reduces the relative risk of death by 30% in patients with severe heart failure.3Although there is a risk of hyperkalaemia,4 spironolactone is a well-known and inexpensive drug and is unlikely to be superseded until more data about eplerenone are available.
