Spironolactone safety questioned- Adverse events more common in older heart failure patients

A new study has questioned the safety profile of spironolactone as it has found that adverse events are more common in older heart failure patients due to the drug. The efficacy of spironolactone was consistent across age categories in patients with heart failure with preserved ejection fraction (HFpEF), but the treatment-related adverse events were more common in participants aged 65 or older, according to a recent study. In simpler words, the potassium-sparing diuretic may put older HFpEF patients at risk for adverse events regardless of lessened dosing regimens.

The study, presented at the Heart Failure Society of America (HFSA) 2019 Scientific Sessions, support guideline recommendations for spironolactone use in appropriately selected HFpEF regardless of age, but underscore that closer laboratory surveillance is critical in older individuals. The study was also published in the Journal of Cardiac Failure.

Spironolactone a popular drug for resistant heart failure is available in India as Aldactone and is also availabe as in combination with other diuretics.

Orly Vardeny, of the University of Minnesota Medical School, and colleagues examined efficacy and safety of spironolactone by age in the Americas region (N=1767) of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial - an international, prospective, randomized, double-blind trial comparing spironolactone to placebo in 3445 patients with HFpEF.

Patients were aged 50 years or older with at least 1 symptom and 1 sign of chronic HF, left ventricular ejection fraction of 45% or greater, controlled systolic blood pressure, and serum potassium levels less than 5 mEq/L.

Investigators limited participant assessment to patients enrolled in the Americas region (n= 1767). They assessed for a pair of primary endpoints designed to indicate efficacy and safety: composite of cardiovascular death, aborted cardiac arrest, and hospitalization for HF; and the discontinuation of study medication due to hyperkalemia, worsening renal function, gynecomastia, or intolerance.

Patients were subcategorized by 3 age groups: <65 years (n= 492); 65-74 years (n= 555), or ≥75 (n= 720). They were randomized to either 15 mg daily spironolactone—with an option to increase every 4 weeks over 4 months, up to 45 mg—or placebo.

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Key findings include:

• Participants in the older age category were more commonly female, Caucasian, and had lower body mass index and eGFR compared to younger age categories.


• The adjusted incidence rates of the primary composite outcome of cardiovascular death, aborted cardiac arrest, and hospitalization for HF, per 100 patients-years, were lower in each of the treated patient age groups (8.7; 12.7; 14.5) than that of the equivalent placebo groups (12.1; 13.6; 15.3).


• All-cause mortality rates, which increased gradually among the older age groups, were also generally lower for treated patients (4.4; 6.0; 9.0) than for patients on placebo (4.4; 8.1; 10.1).


• The efficacy benefits were most pronounced among older patients.


• Rates for hyperkalemia (5.6; 13.5; 12.2) worsening renal function (7.4; 7.3; 6.7), and hypotension (12.0; 19.4; 13.4) were more significant among a majority of the treated age groups than their respective placebo-treated counterparts.

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Though there was no heterogeneity among rates of primary efficacy endpoint in patient age groups, investigators were able to conclude there were notable differences in safety outcomes among older HFpEF patients treated with spironolactone. The authors wrote that such findings come into consideration when prescribing older, at-risk patients with HF.

To read the complete study log on to https://doi.org/10.1016/j.cardfail.2019.07.036