Table 6. Clinical practice-based recommendations.
ACEi, angiotensin-converting enzyme inhibitors; AMI, acute myocardial infarction; ARNi, angiotensin receptor neprilysin inhibitors; BNP, brain natriuretic peptide; eFGR, estimated glomeruli filtration rate; HF, heart failure; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; MRA, mineralocorticoid receptor antagonists; RAASi, renin-angiotensin-aldosterone system inhibitors; TOPCAT, treatment of preserved cardiac function heart failure with an aldosterone antagonist trial
| Clinical practice-based recommendations |
| · In HFrEF, MRA may provide cardiovascular protection beyond its diuretic and potassium-sparing properties. |
| · In HFrEF, Spironolactone has specific neurohormonal activity on the RAAS system, which includes a reduction in BNP and an increase in AT II and aldosterone due to feedback. It should be emphasized that despite treatment with ACEi, there may be elevated angiotensin 2, which stimulates aldosterone levels via an escape phenomenon. |
| · In HFrEF, suppression of collagen turnover changes and reduction in markers of cardiac fibrosis may be one of the extrarenal mechanisms of the beneficial effect of spironolactone and eplerenone. |
| · In HFrEF patients who are symptomatic despite RAASi/ARNI/Beta-blockers and with Serum K+ < 5.0 meq/L and eGFR > 30 ml/min/m2, MRAs such as spironolactone or eplerenone are recommended to reduce the risk of mortality and hospitalization. |
| · Earlier introduction of eplerenone in the pre-discharge hospital setting, especially in post-AMI patients without contraindications, is likely beneficial. In chronic HF and hospitalized HF, it may be beneficial to initiate MRA early after ACEi and beta blockers. Additionally, it must be emphasized that eplerenone and spironolactone should be initiated only after ACE-/ARBs and beta blockers. |
| · In HFrEF patients, spironolactone may reduce the incidence of ventricular premature contractions and ventricular tachycardia. |
| · There are no head-to-head comparisons of eplerenone and spironolactone in HF. However, eplerenone may benefit the ischemic subset of HFrEF and may be more suitable for male patients who develop breast tenderness or gynecomastia. Spironolactone may be preferred in patients from poor socioeconomic groups. |
| · In HFpEF patients with specific selection criteria like phenogroup 3 from the TOPCAT sub-study (and with EF >45%, elevated BNP levels or HF admission within 1 year, estimated glomerular filtration rate >30 mL/min, creatinine <2.5 mg/dL, potassium <5.0 mEq/L), aldosterone receptor antagonists such as spironolactone or eplerenone may be considered to decrease hospitalizations. |
| · In HFmrEF patients who are symptomatic despite RAASi and beta-blockers and who have serum K+ < 5.0 meq/l and with eGFR> 30 ml/min/m2, Spironolactone may be considered. |
| · In HF patients on MRAs, routine testing for renal function and electrolytes (particularly K+) is recommended. |
| · Low-dose MRA at initiation (25 mg of eplerenone or spironolactone) should be considered. MRAs should be up-titrated after 4–8 weeks. |
| · Check serum electrolytes and serum creatinine at 1 and 4 weeks after starting/increasing dose and at 8 and 12 weeks; 6, 9, and 12 months; 4 months thereafter. Repeat electrolyte estimation is recommended for confirmation of initial high levels of serum K+ to avoid lab errors. Alternative causes of hyperkalemia should be ruled out. |
| · If K+ rises above 5.5 mmol/L or creatinine, rises to 2.5 mg/dL, or eGFR < 30 ml/min/m2, the dose of MRA should be reduced to half, and blood chemistry monitored closely. |
| · If K+ rises to >6.0 mmol/L or creatinine to 3.5 mg/dL eGFR <20 ml/min/1.73 m2, stop MRA and seek specialist advice. |
| · There are no head-to-head comparisons of eplerenone and spironolactone in HF and no evidence that either is more beneficial in HFrEF with Diabetes. |
| · In diabetic patients, serum electrolytes should be monitored vigilantly, irrespective of renal function. |