The safety of spironolactone treatment in patients with heart failure

Abstract

Spironolactone is a common cause of hyperkalaemia when used in combination with either an ACE inhibitor or an AT2 antagonist. This reinforces the need for care when extrapolating the results of clinical trials to daily clinical practice.

Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases

“…The risks of developing hyperkalemia when using ACEIs along with spironolactone and potassium supplements to treat chronic heart failure (CHF) increased in patients with concomitant renal failure [4][5][6][7]. Furthermore, the severity of hyperkalemia increased when ACEIs were used concomitantly with spironolactone [8].…”

Aldosterone antagonists in the treatment of heart failure

“…6,[70][71][72] This may be due to exclusion of high-risk patients, increased frequency of monitoring, different dosages of aldosterone antagonists, and less frequent use of concurrent medications affecting electrolyte balance, compared with usual practice. RALES and EPHESUS excluded patients with serum creatinine concentrations of ≥2.5 mg/dL or serum potassium concentrations of ≥5.0 mmol/L.…”

“…Since that time, several case reports and case series have linked aldosterone antagonism in heart failure with life-threatening hyperkalemia, especially in combination with ACE inhibitors or ARBs. [70][71][72][73][74][75][76] A Canadian-based retrospective analysis evaluated the prescribing Am J Health-Syst Pharm-Vol 63 patterns of spironolactone and hyperkalemia-associated hospitalizations in patients age 66 years or older. 6 The prescription rate of spironolactone for patients who had been hospitalized for heart failure increased from 30 Importantly, this trial did not evaluate causality.…”

“…Diabetes has been associated with hyperkalemia in heart failure patients taking an aldosterone inhibitor. 70,71,76,77,79 In a retrospective review, Anton and colleagues 70 The mechanism of increased risk of hyperkalemia in diabetic patients is not completely understood. Chronic diabetes mellitus is a common cause of hyporeninemic hypoaldosteronism, which causes decreased aldosterone availability and subsequent potassium retention.…”

External Validity and Model Validity: A Conceptual Approach for Systematic Review Methodology

“…We will use an example illustrated by Persaud and Mamdani [18] of spironolactone use in heart failure which illustrates the danger in relying on specific selection criteria that is internally but not externally valid.

“The Randomized Spironolactone Evaluation Study (RALES) was prematurely ended when its conclusion became clear: “Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure” [23]. But, compared with the RALES, a retrospective study found a significantly higher incidence of hyperkalemia when spironolactone was combined with standard therapy [24]. Further, a population time-series analysis showed that the increase in spironolactone prescription among elderly congestive heart failure (CHF) patients after the RALES was followed by an increase in hyperkalemia-related hospitalizations and hyperkalemia-related hospital deaths for this patient group [25].

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