A randomized, double-blind study of fenofibric acid plus rosuvastatin compared with rosuvastatin alone in stage 3 chronic kidney disease
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Debra L Weinstein1, Laura A Williams, Dawn M Carlson
1Zasa Clinical Research, Boynton Beach, FL 33472, USA. dweinstein@atlanticclinicalresearch.com
Insights
Fenofibric acid (FA) plus rosuvastatin (R) significantly improved triglycerides and HDL-C in patients with stage 3 CKD and mixed dyslipidemia. This combination therapy demonstrated an acceptable safety profile compared to rosuvastatin alone.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Patients with chronic kidney disease (CKD) often present with mixed dyslipidemia, increasing their cardiovascular disease (CVD) risk.
- Statins are effective in reducing LDL-C, but combination therapy with fibrates may offer additional lipid-modulating benefits.
Purpose of the Study:
- To evaluate the short-term efficacy and safety of fenofibric acid (FA) plus rosuvastatin (R) combination therapy.
- To assess the impact on lipid parameters and estimated glomerular filtration rate (eGFR) in patients with stage 3 CKD and mixed dyslipidemia.
Main Methods:
- A multicenter, randomized study comparing FA + R combination therapy versus R monotherapy.
- Patients received escalating doses of R (5 mg then 10 mg) with or without FA 45 mg for 16 weeks, followed by an 8-week washout period.
- Primary and secondary endpoints focused on changes in triglycerides and HDL-C levels.
Main Results:
- FA + R significantly reduced triglycerides (median % change: -42.6% vs -29.7% at week 16) and increased HDL-C (mean % change: 17.3% vs 8.9% at week 16) compared to R monotherapy.
- Adverse event rates were comparable between the combination and monotherapy groups.
- Serum creatinine levels showed a slight, reversible increase during treatment, returning to baseline after washout.
Conclusions:
- Fenofibric acid (FA) plus rosuvastatin (R) combination therapy demonstrated superior efficacy in improving triglyceride and HDL-C levels compared to rosuvastatin monotherapy.
- The combination therapy exhibited an acceptable safety profile in patients with stage 3 CKD and mixed dyslipidemia.
- FA + R represents a potential therapeutic option for managing dyslipidemia in this high-risk patient population.
Background:
Patients with chronic kidney disease (CKD) often have mixed dyslipidemia and high cardiovascular disease risk. Although statins reduce LDL-C, adding a fibrate may further improve lipid parameters.
Objective:
This multicenter, randomized study evaluated the short-term efficacy and safety profile of fenofibric acid (FA) + rosuvastatin (R) combination therapy for improving lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. The study also assessed estimated glomerular filtration rate after study drug washout.
Methods:
Patients received FA 45 mg + R (5 mg for 8 weeks, then 10 mg for 8 additional weeks) or R monotherapy (5 mg for 8 weeks, then 10 mg for 8 additional weeks), followed by an 8-week washout period. Primary and secondary end points were percent changes in triglycerides and HDL-C, respectively, from baseline to week 8.
Results:
FA 45 mg + R 5 mg, compared with R 5 mg, resulted in significant improvements in triglycerides (median % changes: week 8, -38.0% vs -22.4%, P < 0.001; week 16, -42.6% vs -29.7%, P < 0.001) and HDL-C (mean % changes: week 8, 16.9% vs 7.8%, P < 0.001; week 16, 17.3% vs 8.9%, P < 0.001). Adverse event rates were similar between groups (70.7% with FA + R vs 68.6% with R). Mean serum creatinine level at baseline was 1.36 mg/dL in the FA + R group and 1.38 mg/dL in the R group. The final treatment serum creatinine value, defined as the last nonmissing postbaseline value collected within 30 days after the last dose of study drug, was 1.52 mg/dL with FA + R (vs 1.41 mg/dL with R; P < 0.001), which then decreased to 1.39 mg/dL after the 8-week washout (vs 1.42 mg/dL with R).
Conclusions:
The data suggest that, after 16 weeks of therapy, FA + R has an acceptable safety profile and improved TG and HDL-C efficacy versus R. FA + R combination therapy may thus further improve lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. ClinicalTrials.gov identifier: NCT00680017.
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