Association between dosing of spironolactone and outcomes in heart failure with preserved ejection fraction patients combined with chronic kidney disease------Balance of efficacy and risk

Abstract

Aims: Few studies have compared the association between dosing of spironolactone and outcomes in patients with heart failure with preserved ejection fraction (HFpEF), and whether spironolactone dose could significantly affect the prognosis of HFpEF patients combined with chronic kidney disease (CKD) remains unclear. Our aim was to directly compare ‘high vs. low’ doses of spironolactone in an attempt to find a benefit-risk-balanced point, and infer an adequate dose for HFpEF with CKD patients.Methods: Overall, 4,321 symptomatic heart failure inpatients were initially screened from January 2013 to December 2019, and all enrolled patients were followed-up for 36 months; After including patients who meet the diagnostic criteria of HFpEF and CKD with ejection fraction > 45% and estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, a total of 387 patients was selected. Primary outcome was a composite of all-cause death, heart failure (HF) hospitalization and non-fatal stroke. The key safety outcome was hyperkalemia rates during the follow-up period.Results: The primary outcome event rates in patients with or without spironolactone were 12.74 and 21.45 per 100 person-years, respectively. Compared with patients not taking spironolactone, the adjusted hazard ratio (HR) [95% confidence interval (CI)] was 0.55 (0.38–0.79) with spironolactone group for primary outcomes. After grouped by the daily dose of spironolactone, low-dose group (≤ 40 mg) was associated with lower relative risk for the primary efficacy outcome [adjusted HR (95% CI) was 0.43 (0.23–0.81), 0.50 (0.33–0.76) and 0.74 (0.36–2.79) with < 40 mg, 40 mg and >40 mg, respectively]. During 3-year follow-up, the risk for hyperkalemia was amplified in the higher dose group (>40 mg) while showed no significant difference compared with low dose group (p = 0.425).Conclusion: HFpEF with CKD patients using spironolactone had lower risk of adverse cardiovascular outcomes. And the use of low-dose spironolactone (≤ 40 mg) showed the best efficacy and safety, therefore we may recommend ≤ 40 mg as the optimal initial dose for these patients. However, this was a relatively small sample size, retrospective study, and further adequately powered randomized trials are needed to verify these results.

Retrospective study on the short-term efficacy of different doses of Spironolactone in patients with heart failure of ischemic cardiomyopath and the influence of ventricular remodeling markers

“…Currently, many scholars recommend the longterm use of low-dose Spironolactone to mitigate ventricular remodeling and enhance the quality of life in patients with CHF [24]. However, in the early stages of HFIC, rapidly reducing the circulatory load and the expression of ventricular remodeling damage molecules, blocking the activation of the RAAS, and preventing and treating ventricular remodeling to improve clinical symptoms are of substantial clinical importance.…”

“…Studies have shown that inhibiting RAAS activation is fundamental in CHF treatment, significantly enhancing therapeutic outcomes and preventing ventricular remodeling [6,7]. Am J Cardiovasc Dis 2024;14(1): [21][22][23][24][25][26][27][28] Currently, the clinical application of Angiotensin-Converting Enzyme Inhibitors (ACEI) in RAAS effectively reduces circulating aldosterone levels, but instances of aldosterone may escape are reported, with some studies suggesting this occurs in up to 38% of cases [8,9]. Evidence indicates that integrating Spironolactone into conventional CHF therapy can substantially mitigate the aldosterone escape phenomenon [10,11].…”

Investigation of the efficacy of beta-blockers and reninangiotensin-aldosterone system inhibitors in chronic heart failure with preserved ejection fraction

“…In an earlier study, the role of spironolactone in improving myocardial diastolic function and exercise capacity in HfpEF patients was investigated, and the result revealed that spironolactone significantly ameliorated left ventricular (LV) diastolic dysfunction, LV remodeling, and NT-proBNP levels, but did not enhance quality of life or exercise capacity [18]. However, another study revealed that HfpEF patients on spironolactone presented a reduced risk of adverse cardiovascular outcomes and the use of low-dose spironolactone (≤ 40 mg) displayed its optimal efficacy and safety profile [19]. Some scholars reported an improvement in cardiac structure/function in patients using spironolactone, but no enhancement in exercise capacity [20].…”

Circulating osteoprotegerin levels and cardiovascular outcomes in patients with pre-dialysis chronic kidney disease: results from the KNOW-CKD study

“…Cardiovascular disease (CVD) remains a primary cause of mortality among patients with chronic kidney disease (CKD) 1 , 2 . Beyond the notable prevalence of coronary artery disease 3 , 4 , heart failure, stemming from either systolic or diastolic dysfunction, further exacerbates the adverse cardiovascular outcomes in this population 5 , 6 . Hence, the early stratification of CKD patients at heightened risk for cardiovascular events (CVEs) is crucial.…”