This article is more than 5 years old. Information may no longer be current.
Spironolactone effective as HFpEF treatment regardless of kidney function, but safety less clear
The efficacy of spironolactone in patients with HF with preserved ejection fraction was consistent across the range of kidney function, although adverse events were higher in those with chronic kidney disease, researchers reported.
“These data supported use of spironolactone to treat HFpEF patients with advanced chronic kidney disease only when close laboratory surveillance is possible,” Iris E. Beldhuis, BSc, from the cardiovascular division of the department of medicine at Brigham and Women’s Hospital, and colleagues wrote.
The researchers analyzed 1,767 patients from the TOPCAT study of spironolactone vs. placebo in symptomatic HFpEF to determine any association between baseline estimated glomerular filtration rate (eGFR) and safety and efficacy outcomes. Patients were stratified into three groups: eGFR of at least 60 mL/min/1.73 m2 (mean age, 69 years; 49% women), 45 mL/min/1.73 m2 to 60 mL/min/1.73 m2 (mean age, 73 years; 47% women) or less than 45 mL/min/1.73 m2 (mean age, 75 years; 56% women). The analysis was limited to patients from Argentina, Brazil, Canada and the United States.
The primary efficacy outcome was a composite of CV death, HF hospitalization and aborted cardiac arrest. Safety outcomes of interest included hyperkalemia, worsening renal function and drug discontinuation for adverse events.
Spironolactone effective
Across all categories of eGFR, the spironolactone group had lower risk for the primary efficacy outcome compared with the placebo group (HR = 0.82; 95% CI, 0.69-0.98; P for interaction = .13; P for interaction as a continuous variable = .17), the researchers wrote.
In addition, the spironolactone group had lower relative risk for hypokalemia but higher relative risk for hyperkalemia, worsening renal function and drug discontinuation, they wrote.
At 4 years, absolute risk for adverse events prompting drug discontinuation was highest in those with the worst renal function (P for interaction = .003), according to the researchers.
“Although spironolactone efficacy appeared consistent across eGFR categories with regard to all outcomes that were examined, except myocardial infarction and stroke, the absolute risk of permanent study drug discontinuation was amplified in lower eGFR categories, suggesting a less favorable balance of safety and efficacy in patients with lower eGFR,” Beldhuis and colleagues wrote. “These data emphasize an imperative for close laboratory surveillance among patients with HFpEF and an eGFR of < 45 mL/min/1.73 m2 who receive spironolactone.”
Commit to monitoring
In a related editorial, Patrick Rossignol, MD, PhD, and João Pedro Ferreira, MD, PhD, both from the Université de Lorraine, Inserm, Centre d’Investigations Cliniques-Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT, Nancy, France, wrote: “Unease regarding [worsening renal function] and hyperkalemia is probably excessive in some instances, and, in any event, should probably not be used as a justification for suboptimal use of life-prolonging therapies. These concerns should instead be positively converted to a firm commitment to perform mindful biological monitoring.” – by Erik Swain
Disclosures: Beldhuis reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Ferreira reports he received consultant fees from Novartis. Rossignol reports he has financial ties with Bayer, CardioRenal, CVRx, Fresenius, Idorsia, Novartis, Novo Nordisk, Stealth Peptides and Vifor.