Mineralocorticoid Receptor Antagonist Initiation

Mineralocorticoid receptor antagonists reduce death and admission in heart failure with reduced ejection fraction and after myocardial infarction with heart failure or diabetes, and lower pressure in resistant hypertension, primary aldosteronism and cirrhotic ascites. Start when potassium is under 5.0 mmol/L and eGFR is over 30 mL/min/1.73 m2. The main risks are hyperkalaemia and kidney injury, so monitoring is intensive in the first 3 months.

Baseline. Potassium, creatinine, eGFR, pressure and a review of potassium supplements, NSAIDs, trimethoprim and salt substitutes containing potassium.

Class choice. Spironolactone is first choice. Eplerenone avoids gynaecomastia, which occurs in about 1 in 10 men on spironolactone.

Spironolactone. Heart failure 12.5 to 25 mg orally once daily, increased after 4 weeks to the target of 25 to 50 mg daily. Resistant hypertension 25 mg once daily, up to 50 mg.

Eplerenone. 25 mg orally once daily, increased after 4 weeks to 50 mg daily. If eGFR is 30 to 49 mL/min/1.73 m2, start 25 mg on alternate days and increase to 25 mg daily.

Cirrhotic ascites. Spironolactone 100 mg orally once daily with furosemide 40 mg once daily, adjusted in that ratio to a maximum of 400 mg and 160 mg daily.

Special groups. In older adults start at 12.5 mg. In pregnancy avoid, since antiandrogen effects on the foetus occur. Spironolactone passes into breast milk in small amounts and is usually compatible. In hepatic impairment other than ascites, use with care. In creatinine clearance under 30 mL/min do not start. In diabetes, risk of hyperkalaemia is greater.

Interactions. ACE inhibitors, angiotensin receptor blockers, sacubitril valsartan, potassium supplements, trimethoprim, NSAIDs, ciclosporin and strong CYP3A4 inhibitors (eplerenone only, such as clarithromycin and ketoconazole).

Schedule. Potassium and creatinine at 1 week and 4 weeks after starting, at 8 and 12 weeks, at 6, 9 and 12 months, and then every 4 months. Repeat after each dose change or intercurrent illness.

Dose rules. Halve the dose for potassium of 5.5 to 5.9 mmol/L. Stop at 6.0 mmol/L or over, or if creatinine rises over 100% or reaches 310 micromol/L.

Potassium binders. Patiromer 8.4 g orally once daily or sodium zirconium cyclosilicate 10 g three times daily for up to 48 hours and then 5 to 10 g once daily may allow continued treatment, where available.

Sick day rule. Withhold during vomiting, diarrhoea or poor intake.

Switching. Change spironolactone to eplerenone for gynaecomastia or breast pain.

Stopping. Stop for hyperkalaemia that does not respond, acute kidney injury, or eGFR under 30 mL/min/1.73 m2 on repeat testing.

Common errors. Starting with potassium already high, omitting the 1 week blood test, and combining with potassium supplements.

Referral and escalation. Refer for recurrent hyperkalaemia, rapid eGFR decline or the need for a binder.