Spironolactone Improves the All-Cause Mortality and Re-Hospitalization Rates in Acute Myocardial Infarction with Chronic Kidney Disease Patients

Abstract

Background: Mineralocorticoid receptor antagonists (MRA) improve outcomes in chronic kidney disease (CKD) and acute myocardial infarction (AMI) patients. However, the lack of evidence regarding long-term clinical outcomes in the use of MRA, including spironolactone, in patients with AMI combined with CKD.Objectives: This study aimed to investigate whether spironolactone could significantly reduce the risk of all-cause mortality and re-admission in patients with AMI and CKD.Methods: In this single center, observational, retrospective, registry based clinical study, a total of 2,465 AMI patients were initially screened; after excluding patients with estimated glomerular filtration rate more than 60 ml/min/1.73 m2, 360 patients in the standard treatment group and 200 patients in the spironolactone group met the criteria. All enrolled patients follow-up for 30 months. The primary outcomes were all-cause mortality and re-admission. The key safety outcome was hyperkalemia rates during the 30 months follow-up period.Results: 160 (44.4%) and 41 (20.5%) patients in the standard treatment and spironolactone groups died, respectively [hazard ratio (HR): 0.389; 95% confidence interval (CI): 0.276–0.548; p < 0.001]. Re-admission occurred in 217 (60.3%) and 95 (47.5%) patients in the standard treatment and spironolactone groups, respectively (HR: 0.664; 95% CI: 0.522–0.846; p = 0.004). The spironolactone group was divided into two based on the daily dose, low dose group (no more than 40 mg) and high dose group (more than 40 mg); the differences in the mortality rate between low dose group (16.7%) and the standard treatment group (44.4%) (HR: 0.309; 95% CI: 0.228–0.418; p < 0.001) and high dose group (34.1%) (HR: 0.429; 95% CI: 0.199–0.925; p = 0.007) were significant. The differences in re-hospitalization rate between low dose group (43.6%) and the standard treatment group (60.3%) (HR: 0.583; 95% CI: 0.457–0.744; p < 0.001) and high dose group (61.4%) (HR: 0.551; 95% CI: 0.326–0.930; p = 0.007) was significant. Hyperkalemia occurred in 18 (9.0%) and 18 (5.0%) patients in the spironolactone group and standard treatment group, respectively (HR: 1.879; 95% CI: 0.954–3.700; p = 0.068). Whereas, Hyperkalemia occurred in high dose group (20.5%) significantly more often than in the standard treatment group (p < 0.001) and low dose group (5.8%) (p = 0.003).Conclusion: Using MRA, such as spironolactone, may substantially reduce the risk of both all-cause mortality and re-admission in patients with AMI and CKD; the use of low-dose spironolactone has the best efficacy and safety. However, this was a relatively small sample size, single center, observational, retrospective, registry based clinical study and further prospective evaluation in adequately powered randomized trials were needed before further use of spironolactone in AMI with CKD population.

Real-world evidence for steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease

“…For example, Blankenburg et al [ 14 ] presented results for overall CKD, CKD in T2D, as well as CKD (with or without T2D) and HF populations separately, and Tseng et al [ 19 ] reported results for overall CKD, CKD and HF, as well as for CKD and history of CVD. In addition, Qu et al [ 20 ] reported results for overall CKD and CKD in diabetes.…”

“…In the Yang et al study [ 26 ], the difference between the incidence of all-cause death in spironolactone users versus non-users was not significant (event rates 64.42 vs. 60.47/1000 person-years, p = 0.432). In the Qu et al [ 20 ] study, spironolactone use was related to significantly lower risk of all-cause mortality compared to standard treatment (HR = 0.389, 95% CI [0.276; 0.548], p < 0.001). Moreover, the reduction in the risk of all-cause mortality in spironolactone users was consistent among analyzed subgroups, including patients with different levels of eGFR.…”

“…In the Qu et al [ 20 ] study, spironolactone use was associated with significantly lower risk of re-hospitalization compared to standard treatment (HR = 0.664 95% CI [0.522; 0.846], p = 0.004). Additionally, the reduction in the risk of re-hospitalization among spironolactone users was consistent among analyzed subgroups including patients with different levels of eGFR.…”

“…Gillis et al [ 28 ] observed no significant difference (p = 0.60). In the Qu et al [ 20 ] study, assessing CKD patients with acute myocardial infarction, hyperkalemia occurred in the spironolactone group more often than in the standard treatment group (9.0%, 5.0%, respectively, HR = 1.879, 95% CI [0.954; 3.700], p = 0.068). In the same study, hyperkalemia occurred in 5.0%, 9.8% and 8.5% in the CKD stage 3, 4 and 5 groups, respectively, however the differences among the CKD groups were not statistically significant (p < 0.133).…”

“…This study included 19,582 patients of whom 2295 were MRA users. Another study conducted by Qu et al [ 20 ] in China and published as a manuscript, assessed spironolactone in CKD in diabetes. This study included 560 patients of whom 200 were spironolactone users.…”