Spironolactone
Saikrishna Patibandla, Joseph Heaton, Htoo Kyaw
PMID: 32119308
Abstract:
Spironolactone has indications in both certain cardiovascular diseases and non-cardiovascular disease entities. Spironolactone is FDA approved for the treatment of heart failure with reduced ejection fraction (HFrEF), resistant hypertension, primary hyperaldosteronism, edema secondary to cirrhosis, edema secondary to a nephrotic syndrome that is not adequately controlled using alternative therapies, and hypokalemia. The Randomized Aldactone Evaluation Study (RALES) was a landmark trial that used spironolactone in New York Heart Association (NYHA) class III-IV HFrEF patients with an ejection fraction less than 35%, and the trial was stopped early due to but not limited to positive findings including a 30% relative risk reduction in all-cause mortality. In the 2017 American College of Cardiology heart failure guidelines, spironolactone is indicated in NYHA class II-IV HFrEF patients who have a creatinine clearance greater than 30 mL/min and a serum potassium level less than 5 mEq/L, and the guidelines also mention that select heart failure with preserved ejection fraction (HFpEF) patients may benefit from spironolactone use to help in reducing the number of hospitalizations. There is some evidence that spironolactone may reduce myocardial fibrosis, reduce left ventricular mass, and decrease the amount of extracellular volume expansion in HFpEF patients. This medication is not yet generally recommended for end-stage renal disease patients either on or not on dialysis; even though more large randomized controlled trials are needed, some reports do suggest that it would be well tolerated in chronic kidney disease patients if clinicians carefully manage the risk of hyperkalemia. The definition of resistant hypertension is elevated blood pressure above the goal despite a patient being on optimal doses of three different antihypertensive agents of which one is a diuretic is another condition for which clinicians can prescribe spironolactone. The typical triple antihypertensive regimen in these patients is a thiazide diuretic, calcium channel blocker, and wither an angiotensin-converting enzyme inhibitor or an aldosterone receptor antagonist. Researchers tested low dose spironolactone as an agent added on in both White race and African American patients with resistant hypertension with and without primary hyperaldosteronism, and results showed it to help lower blood pressure when added to these patients' multidrug antihypertensive regimens. Spironolactone was also tested against bisoprolol and doxazosin to determine which of the three was the most effective fourth agent for treating resistant hypertension, and research showed spironolactone to be superior to the other two in reducing systolic home blood pressure in these patients. A study tested spironolactone against clonidine as the fourth agent in treating resistant hypertension and found to be non-inferior base on the primary endpoints of the trial and preferable to clonidine based on secondary endpoints of 24-hour systolic and diastolic blood pressure as well as diastolic daytime ambulatory blood pressure being lowered greater by spironolactone than by clonidine. Spironolactone is considered the main option for the treatment of ascites in cirrhosis after the dietary salt restriction is not sufficient. The typical starting dose ratio of oral furosemide to spironolactone is 40 mg to 100 mg, respectively. A study in children with severe edema secondary to nephrotic syndrome showed that oral spironolactone in conjunction with intravenous furosemide was safe and helpful in treating these children who had edema with volume expansion. Spironolactone was studied concurrently with metolazone in patients with cirrhosis and nephrotic syndrome and found to be effective adjunctively, and it mitigated the hypokalemia associated with metolazone use.
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