Effects and Safety of Statin and Ezetimibe Combination Therapy in Patients with Chronic Kidney Disease: A Systematic Review and Meta‐Analysis

Abstract

The efficacy and safety of statin and ezetimibe combination therapy in patients with chronic kidney disease (CKD) remains unclear. To assess the effect of statin and ezetimibe combination therapy on controlling lipid profiles and reducing cardiovascular events in patients with CKD, we conducted a systematic review and meta‐analysis. We selected randomized controlled trials comparing this combination therapy with statin monotherapy or placebo in patients with CKD from the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases published before September 1, 2018 on the Internet. Eight articles on seven studies, with a total of 14,016 patients with CKD, were selected from 412 full‐text articles. Statin and ezetimibe combination therapy had beneficial effects on serum total cholesterol (weighted mean difference (WMD) −20.31 mg/dL, 95% confidence interval (CI), −26.87 to −13.75 mg/dL, P < 0.001), low‐density lipoprotein cholesterol (WMD −17.22 mg/dL, 95% CI, −18.93 to −15.51 mg/dL, P < 0.001), and triglycerides (WMD −15.08 mg/dL, 95% CI, −23.41 to −6.75 mg/dL, P < 0.001) compared with statin monotherapy. Statin and ezetimibe combination therapy significantly reduced all‐cause mortality and major adverse cardiovascular events (risk ratio 0.86, 95% CI, 0.77 to 0.97, P = 0.01). The incidence of adverse events was low, with no significant difference between statin and ezetimibe combination therapy and statin monotherapy. In conclusion, the statin and ezetimibe combination therapy significantly improved serum lipid profiles and reduced risks of all‐cause deaths and major adverse cardiovascular events compared with the control group in patients with CKD.

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“…Our study investigated the effectiveness of ST on the association with mortality risks in three different renal groups. The mortality risk reductions in patients with NRF and CKD were consistent with current evidences (Palmer et al, 2014;Lin et al, 2020). The sample sizes of most previous studies were likely not large enough to include patients with ESRD for analysis.…”

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“…Other signaling pathways associated with proteinuria include the Wnt/β-catenin pathway; elevated expression of Wnt/β-catenin transcripts and proteins has been observed in the podocytes of DKD patients and DKD mouse models, while stable expression of Wnt/β-catenin genes in the podocytes of transgenic mice was shown to induce albuminuria [ 65 ]. In addition, hyperactivation of mTOR is known to induce podocyte hypertrophy and apoptosis of podocytes, which aggravates glomerular disease and proteinuria [ 66 , 67 ]. It is also known that reduced nephrin expression is involved in hyperglycemia-induced albuminuria [ 68 , 69 ].…”