In heart failure patients, spironolactone linked to reduced risk of dementia, Alzheimer’s disease

Andreas Kalogeropoulos, MD, MPH, PhD
Credit: Stony Brook Medicine


In patients with heart failure and reduced ejection fraction (HFrEF), the use of spironolactone may reduce the risk of adverse neurocognitive outcomes, according to new data presented at the Heart Society of America (HFSA) 2023 Annual Scientific Meeting.

An analysis of data from the TriNetX electronic health record network, led by investigators at Stony Brook Medicine, shows that the incidence of Alzheimer’s disease and dementia was reduced in people with HFrEF receiving spironolactone in a propensity score-matched analysis.1

“These findings suggest that spironolactone may have neuroprotective effects in patients with HFrEF, but prospective research is needed to confirm these results and clarify any beneficial mechanisms,” the investigators wrote.1

The connection between heart disease and cognitive decline has fascinated neurologists, cardiologists, primary care, and many others in the medical field. An analysis of data from the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development Study in Young Adults, the Heart Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study was published in 2022, comparing cognitive decline in those with With or without cardiovascular events, it was suggested that people who experienced cardiovascular problems declined significantly faster in the following years in their memory, executive functioning, and global cognition than their counterparts without any events. .2

Citing previous research in rats indicating that increased plasma aldosterone concentration may increase the risk of cognitive impairment and that the use of spironolactone may reduce this effect, Andreas, MD, MPH, PhD, of the department of cardiology at Stony Brook Medicine, said: A team of investigators led by Kalogeropoulos has hypothesized the use. In patients with HFrEF, spironolactone may reduce the risk of new neurocognitive disorders for up to 3 years compared with those not taking the drug. With this in mind, the investigators designed their study as a retrospective analysis of data from US patients in the TriNetX electronic health record database from 2015-2019.1

The primary outcomes of interest were new diagnoses of Alzheimer’s disease, dementia, and any cognitive decline. The investigators reported that Cox proportional hazards models were used to estimate the incidence of each outcome of interest. Of note, propensity score-matching for over 100 clinical characteristics was used to match those with HFrEF who were using spironolactone and those who were not using spironolactone.1

In total, 44,892 individuals were identified for each matching group. The mean age of the spironolactone group was 67.0 (standard deviation, 13.7) years, 59.8% were male, and 65.1% were white. The mean age of the group not using spironolactone was 66.9 (SD, 14.6) years, 59.9% were male, and 65.3% were white.1

When examining incidence counts, the incidence of each event of interest was numerically higher in those not using spironolactone. When analyzed, the study results showed that patients who experienced a reduction in the risk of developing Alzheimer’s disease (hazard ratio) [HR], 0.82; 95% confidence interval [CI]0.72-0.94; P =.005) and dementia (HR, 0.91; 95% CI, 0.85-0.97; P =.006) relative to their counterparts not receiving spironolactone. However, the investigators noted that there was no significant difference in the incidence of cognitive decline with the use of spironolactone (HR, 0.97; 95% CI, 0.93-1.02); P =.226).1

“the occurrence of [Alzheimer disease] “And patients with HFrEF who received spironolactone had less dementia in this propensity score-matched analysis from a large health care database,” the investigators wrote.1


  1. Pestena P, Skopiki H, Halterman M, Kalogeropoulos A. Racial and ethnic disparities in contemporary use of left ventricular assist devices in the United States. Paper presented at: Heart Failure Society of America 2023 Annual Scientific Meeting; October 6 – 9; Cleveland, OH. Accessed October 7, 2023.
  2. Cognitive skills declined rapidly in the years following the heart attack. American Heart Association. February 3, 2022. Accessed October 7, 2023.

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