Racial Differences in Patients' Potassium Concentrations During Spironolactone Therapy for Heart Failure

Cavallari, Larisa H.; Fashingbauer, Lucy A.; Beitelshees, Amber L.; Groo, Vicki L.; Southworth, Mary Ross; Viana, Marlos A. G.; Williams, Russell B.; Dunlap, Stephanie H.

doi:10.1592/phco.24.8.750.36076

Cited by 15 publications

(9 citation statements)

References 21 publications

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“…Our findings are consistent with 2 other analyses that also reported less pronounced changes in serum potassium in AA patients with HF who were taking spironolactone compared with non-AA patients. 10,11 Patients with HF may be at higher risk for hyperkalemia from renin-angiotensin-aldosterone system blockers because of inherently diminished renal perfusion, reducing delivery of sodium at distal tubule sites, which results in decreased potassium excretion.…”

Section: Discussionmentioning

confidence: 99%

Race Influences the Safety and Efficacy of Spironolactone in Severe Heart Failure

Vardeny

Cavallari

Claggett

et al. 2013

Circ: Heart Failure

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Background— The incidence of hyperkalemia caused by mineralocorticoid receptor antagonists may vary by race, but whether race influences efficacy of mineralocorticoid receptor antagonists in heart failure (HF) is unknown. Methods and Results— We assessed hyperkalemia and outcomes in African Americans (AAs; n=120) and non-AAs (n=1543; white 93%) with New York Heart Association (NYHA) class III or IV HF and left ventricular dysfunction who were randomized to spironolactone, titrated to 25 or 50 mg daily or placebo, in the Randomized Aldactone Evaluation Study (RALES). AA participants were significantly younger, less likely to have an ischemic HF pathogenesis, more likely to be NYHA functional class IV, and more likely to have a higher estimated glomerular filtration rate and heart rate, less hypertension, diabetes mellitus, or history of myocardial infarction compared with non-AA participants. Potassium increased with spironolactone in non-AAs (4.29±0.5–4.55±0.49 mmol/L) but not in AAs (4.32±0.54–4.31±0.49 mmol/L; race by treatment interaction, P =0.03) during the first month and remained higher throughout the trial. Compared with AAs, non-AAs were more likely to attain maximal spironolactone dose (13.9% versus 5.8%; P =0.04) and had higher rates of hyperkalemia (potassium>5.5 mmol/L; 9.7% versus 4.2%; P <0.046), as well as lower rates of hypokalemia (potassium<3.5 mmol/L; 5.6% versus 17.9%; P <0.001). After adjustment for differences in baseline characteristics and achieved study drug dose, spironolactone reduced the combined end point of death or hospitalization for HF in non-AAs (hazard ratio, 0.63; 95% confidence interval, 0.55–0.73) but not in AAs (hazard ratio, 1.07; 95% confidence interval, 0.67–1.71; P value for interaction=0.032). Conclusions— AAs with HF exhibited less hyperkalemia and more hypokalemia with spironolactone compared with non-AAs and seemed to derive less clinical benefit. These hypothesis-generating findings suggest that safety and efficacy of mineralocorticoid receptor antagonists may differ by race.

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Section: Discussionmentioning

confidence: 99%

Race Influences the Safety and Efficacy of Spironolactone in Severe Heart Failure

Vardeny

Cavallari

Claggett

et al. 2013

Circ: Heart Failure

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“…However, AAs had a significantly better response to eplerenone than to losartan (ARB), whereas no difference in response between these two agents was found in whites 88 . In patients with heart failure treated with spironolactone, AAs exhibit less hyperkalemia compared with whites when treated with MRAs 89 .…”

Section: Predictors Of Renin-angiotensin-aldosterone System Blockade mentioning

confidence: 96%

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

Ghazi

Drawz

2017

F1000Res

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The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice.

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“…Short half-life is important to consider for safety concerns to yield a rapid decrease of active moieties when halting therapy in case of toxic side effects. Racial difference in response to MR blockade may exist: African Americans with heart failure are less responsive to the renal effect of spironolactone and develop less hyperkaliemia (Cavallari et al, 2004); this is not the case with eplerenone (Flack et al, 2003). It has been reported that spironolactone (at micromolar concentrations) inhibits aldosterone biosynthesis (Netchitailo et al, 1985) and blocks enzymes involved in steroidogenesis (Penhoat et al, 1988;Ye et al, 2009).…”

Section: A Steroidal Compoundsmentioning

confidence: 99%

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

2015

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Racial Differences in Patients' Potassium Concentrations During Spironolactone Therapy for Heart Failure

Abstract: Our findings suggest that a large percentage of patients with heart failure, particularly African-Americans, still require potassium supplementation despite treatment with spironolactone and standard vasodilator therapy.

Cited by 15 publications

References 21 publications

Race Influences the Safety and Efficacy of Spironolactone in Severe Heart Failure

Race Influences the Safety and Efficacy of Spironolactone in Severe Heart Failure

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

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