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Aldosterone antagonists in the management of heart failure

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

NICE suggest with respect to use of mineralocorticoid receptor antagonists (MRA) in treating heart failure with reduced ejection fraction (1)

  • an MRA (e.g. spironolactone, eplerenone) should be offered, in addition to an ACE inhibitor (or ARB) and beta-blocker, to people who have heart failure with reduced ejection fraction if they continue to have symptoms of heart failure

  • measure serum sodium and potassium, and assess renal function, before and after starting an MRA and after each dose increment

  • blood pressure must be measured before and after after each dose increment of an MRA

  • once the target, or maximum tolerated, dose of an MRA is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell

  • note that in the 2018 guidance the addition of an MRA is a primary intervention (and not suggested as requiring specialist advice)

For patients who have had an acute MI and who have symptoms and/or signs of heart failure and left ventricular systolic dysfunction, treatment with an aldosterone antagonist licensed for post-MI treatment should be initiated within 3-14 days of the MI, preferably after ACE inhibitor therapy (2)

Notes:

  • in consideration of the use of aldosterone antagonists in the management of heart failure:
    • there is a risk of developing hyperkalaemia when spironolactone is combined with an ACE inhibitor - therefore the combination should be used with caution in those with advanced age and/or reduced renal function.
      • in the RALES study (3) revealed that the addition of spironolactone to ACE inhibitor therapy led to an increased mean serum potassium concentration of 0.3mmol per litre - this increase was not found to be clinically important (NB patients with high serum potassium at baseline were excluded)
    • eplerenone is a more selective aldosterone antagonist and is less likely to cause sexual side effects than spironolactone (4)
      • in the EPHESIS study, eplerenone was shown to improve survival compared with placebo when added to existing medical therapy within 3-14 days following acute MI. Patients (n=6,632) were required to have reduced LVEF (<40%) and diabetes or clinical signs of heart failure
      • during a mean follow up of 16 months, 14.4% of patients receiving eplerenone and 16.7% of patients receiving placebo died (RR 0.85; 95%CI 0.75 to 0.96; NNT=43; P=0.008)
      • rates of severe hyperkalaemia were significantly higher with eplerenone than with placebo (5.5% vs. 3.9%; NNT=63; P=0.002)
    • aldosterone blockage and left ventricular function - systematic review (5)
      • review revealed a 20% reduction in all-cause mortality with the use of aldosterone blockade in a clinically heterogeneous group of clinical trial participants with heart failure and post-MI
        • also showed 3.1% improvement in ejection fraction

An an individual patient level meta-analysis concluded (6):

  • steroidal MRAs reduce the risk of cardiovascular death or heart failure hospitalisation in patients with HFrEF and non-steroidal MRAs reduce this risk in patients with HFmrEF (heart failure with mildly reduced ejection fraction) or HFpEF (heart failure with preserved ejection fraction)

Reference:


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