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Updated: Jul 19, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Fixed-Dose Combination Therapy for the Prevention of Cardiovascular Diseases in CKD: An Individual Participant Data
Sadaf G Sepanlou1, Johannes F E Mann2,3, Philip Joseph3
1Digestive Diseases Research Institute, Tehran University of Medical, Sciences, Tehran, Iran.
Insights
Fixed-dose combination treatments effectively prevent cardiovascular disease in primary prevention. These benefits are even greater for individuals with reduced kidney function, demonstrating enhanced risk reduction.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Pharmacology
Background:
- Fixed-dose combination therapies are established for cardiovascular disease (CVD) primary prevention.
- The impact of these combinations on individuals with chronic kidney disease (CKD) remains less understood.
Approach:
- Individual participant data meta-analysis of 18,162 participants.
- Compared combination therapies (≥2 BP drugs + statin ± aspirin) versus placebo/minimal care.
- Examined differential effects based on estimated glomerular filtration rate (eGFR): low (<60 ml/min/1.73 m²) vs. normal (≥60 ml/min/1.73 m²).
Key Points:
- 18% of participants had low eGFR at baseline.
- Combination therapy significantly reduced the primary composite CVD outcome in both normal and low eGFR groups (HR 0.68 and 0.49, respectively).
- Relative and absolute risk reductions were larger in participants with low eGFR (P-interaction=0.047).
- Aspirin-inclusive strategies showed greater risk reduction in low eGFR individuals.
- No significant differences in side effects were observed across eGFR levels.
Conclusions:
- Fixed-dose combination treatment is effective and safe for CVD primary prevention across all eGFR levels.
- Individuals with low eGFR experience greater relative and absolute risk reductions.
- This highlights the importance of combination therapies in high-risk populations with CKD.
Background:
Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of CKD.
Methods:
We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two BP-lowering drugs and a statin, with or without aspirin versus placebo or minimal care. Here, we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low eGFR (<60 ml/min per 1.73 m 2 ; Chronic Kidney Disease Epidemiology Collaboration formula) compared with a normal eGFR (≥60 ml/min per 1.73 m 2 ). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization.
Results:
At baseline, the mean level of eGFR was 76 ml/min per 1.73 m 2 (SD 17). In total, 3315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) participants in the treatment group compared with 339 (5%) in the control group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P < 0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) participants in the treatment group compared with 130 (8%) in the control group (hazard ratio, 0.49; 95% confidence interval, 0.36 to 0.66; P < 0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies, including aspirin compared with treatments without aspirin. Apart from dizziness, other side effects did not differ between treatment and control groups, regardless of the stage of their kidney function.
Conclusions:
A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR, but relative and absolute risk reductions are larger in individuals with low eGFR.
Podcast:
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000251.mp3.
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