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Low-dose Spironolactone Combined with ACEIs/ARBs May Reduce Cardiovascular Events in Patients with CKD Stages 3b-5: A
Li-Nien Chien1,2, Po-Jen Hsiao3,4,5, Chih-Chien Chiu6,7,8
1Institute of Health and Welfare Policy, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
Insights
High adherence to low-dose spironolactone (25 mg/day) in patients with advanced chronic kidney disease (CKD) on ACE inhibitors or ARBs significantly lowers cardiovascular event risk. This improved adherence did not increase risks of renal failure or hyperkalemia.
Area of Science:
- Nephrology and Cardiovascular Medicine
- Pharmacotherapy in Chronic Kidney Disease (CKD)
- Epidemiological Research using Health Databases
Background:
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are standard treatments for hypertension and CKD but carry risks of renal decline and hyperkalemia.
- Spironolactone reduces cardiovascular events in CKD patients but its use is limited by hyperkalemia concerns.
- This study investigates low-dose spironolactone as an add-on therapy for advanced CKD patients already on ACEIs or ARBs.
Purpose of the Study:
- To evaluate the efficacy and safety of low-dose spironolactone (25 mg/day) as an adjunct therapy in patients with CKD stages 3b-5.
- To assess the impact of adherence to low-dose spironolactone on major adverse cardiovascular events (MACEs), renal function, and hyperkalemia.
- To compare outcomes between patients with high adherence (MPR ≥80%) and lower adherence (MPR <80%) to spironolactone.
Main Methods:
- Retrospective cohort study using Taiwan's National Health Insurance Research Database (2012-2016) including hypertensive CKD patients (stages 3b-5).
- Inverse Probability Treatment Weighting (IPTW) was used to balance baseline characteristics between treatment groups.
- Adherence was measured by Medication Possession Ratio (MPR) over 3 months; outcomes were analyzed using multivariate Cox regression.
Main Results:
- Among 2,623 patients, 55.5% achieved high adherence (MPR ≥80%).
- High adherence (MPR ≥80%) was associated with significantly lower risks of MACEs (aHR=0.71), nonfatal myocardial infarction (aHR=0.54), and heart failure hospitalization (aHR=0.84).
- No significant increase in acute renal failure, chronic renal failure, or hyperkalemia was observed with high adherence (MPR ≥80% or MPR ≥40%).
Conclusions:
- Higher adherence to low-dose spironolactone (25 mg/day) in advanced CKD patients on ACEIs/ARBs is linked to reduced cardiovascular risk.
- This therapeutic approach appears safe, without elevating risks for renal failure or hyperkalemia.
- Findings suggest that optimizing adherence to low-dose spironolactone can be a beneficial strategy in managing CKD patients.
Abstract:
Background: ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed for hypertension and chronic kidney disease (CKD) management, but they can increase the risk of renal function deterioration and hyperkalaemia. Spironolactone, known for reducing cardiovascular events in CKD patients, faces limited use due to the risk of hyperkalaemia. This study evaluates the potential efficacy and complications of low-dose spironolactone as an adjunct therapy in patients with CKD stages 3b to 5 who are maintained on ACEIs or ARBs. Materials and methods: Hypertensive CKD patients (stages 3b-5) from Taiwan's National Health Insurance Research Database (2012-2016) were selected. Inverse probability treatment weighting (IPTW) was applied to balance baseline characteristics between patients treated with and without spironolactone. In this study, adherence to low-dose spironolactone (25 mg/day) was assessed using the medication possession ratio (MPR) over a continuous 3-month period within the first 12 months after initiation. Multivariate Cox regression models were used to compare clinical outcomes between two groups with MPR ≥80% and MPR <80%. The subgroup including poor adherence (MPR ≥40% and MPR <40%) was also evaluated. Results: Of the 2,623 advanced CKD patients on ACEIs/ARBs and spironolactone, 55.5% (n=1,456) had an MPR ≥80% over a median follow-up of 3.9 years. Post-IPTW, both groups were balanced. Patients with MPR ≥80% showed a lower risk of major adverse cardiovascular events (MACEs; aHR = 0.71, 95% CI = 0.57-0.89), nonfatal myocardial infarction (aHR = 0.54, 95% CI = 0.39-0.75), and heart failure hospitalization (aHR = 0.84, 95% CI = 0.72-0.98). No significant risk was observed for acute renal failure (aHR = 0.87, 95% CI = 0.75-1.02), chronic renal failure (aHR = 0.84, 95% CI = 0.71-1.00), or hyperkalaemia (aHR = 0.86, 95% CI = 0.69-1.07) in the MPR ≥80% group. Patients with MPR ≥40% also showed a lower risk of MACEs (aHR =0.78, 95% CI = 0.62-0.99) and nonfatal MI (aHR = 0.66, CI = 0.47-0.93). Conclusion: In Taiwan, higher adherence to low-dose spironolactone (25 mg/day) in ACEI/ARB-treated patients with CKD stages 3b-5 may reduce cardiovascular disease risk without increasing the risk of renal failure or hyperkalaemia.
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