Simvastatin

This narrative review summarizes the evidence for the approved combination of simvastatin and fenofibrate in treating combined dyslipidemia, characterized by high triglycerides and low HDL cholesterol. Because single lipid‑lowering drugs have selective effects on lipoproteins, combination therapy is often needed, but toxicity concerns remain. Drawing from randomized multicenter trials, meta‑analyses, animal studies, and case reports, the review evaluates both the benefits and the risks of the simvastatin‑fenofibrate regimen. It concludes that while the combination can effectively address multiple lipid abnormalities, careful consideration of potential adverse effects—particularly muscle and liver toxicity—is essential in clinical decision‑making.

Fig. 1 Mean relative reduction of total cholesterol levels by adding fibrates. (Tarantino N, et al., 2017)

In primary human trabecular meshwork (HTM) cells cultured in bioengineered extracellular matrix hydrogels, dexamethasone induced pathologic YAP/TAZ nuclear localization, actin stress fiber formation, and myosin light chain phosphorylation. Simvastatin potently blocked these changes, reduced dexamethasone‑driven matrix contraction and stiffening, and lowered fibronectin expression. The effects were comparable to but not exceeding those of Rho kinase inhibition. These findings suggest that simvastatin’s protective effects in glaucoma may be mediated by YAP/TAZ inactivation, linking statin use to reduced glaucoma risk.

Fig. 2 Effects of simvastatin on YAP/TAZ nuclear localization and TGM2 levels in HTM cells. (Yoo H, et al., 2023)