In HFpEF, spironolactone confers worsening renal function but lower CV death risk
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Among patients with HF with preserved ejection fraction enrolled in TOPCAT-Americas, spironolactone increased risk for worsening renal function but lowered risk for CV death regardless of renal function.
Researchers conducted an analysis of 1,767 patients with HFpEF randomly assigned to spironolactone or placebo in the TOPCAT-Americas study and examined the incidence of worsening renal function, defined as doubling of serum creatinine, by treatment assignment.
“The observation from the primary TOPCAT trial was that there was more frequent worsening of renal function by the study definition in the spironolactone-treated patients with HFpEF. We were interested in exploring whether these changes in renal function that are known to be observed with treatment are clinically meaningful or whether they are simply hemodynamic changes,” Akshay Desai, MD, MPH, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, told Healio.
The spironolactone group experienced worsening renal function more frequently compared with the placebo group (spironolactone, 17.8%; placebo, 11.6%; OR = 1.66; 95% CI, 1.27-2.17; P < .001).
Irrespective of treatment, incident worsening renal function was linked to increased risk for the primary endpoint of CV death, HF hospitalization or aborted cardiac arrest (HR = 2.04; 95% CI, 1.52-2.72; P < .001) after multivariable adjustment.
The researchers wrote that there was no interaction between treatment assignment and worsening renal function for the primary endpoint (P for interaction = .11), but among patients who had worsening renal function, those assigned spironolactone had lower risk for CV death (P for interaction = .003) and all-cause mortality (P for interaction = .001) compared with those assigned placebo.
“The implications of worsening renal function are less ominous in patients treated with spironolactone than if it happens in patients treated with placebo,” Desai told Healio.
Future studies investigating epidemiology, pathophysiology and treatment strategies related to renal dysfunction in HFpEF are warranted, the researchers wrote.
For more information:
Akshay Desai, MD, MPH, can be reached at adesai@bwh.harvard.edu.
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