Fenofibrate (Lipidil): A Comprehensive Clinical and Pharmacological Review

1.0 Introduction: Fenofibrate and the Management of Dyslipidemia

1.1 The Clinical Challenge of Dyslipidemia

Dyslipidemia, a disorder characterized by abnormal concentrations of lipids and lipoproteins in the blood, represents a cornerstone of modern cardiovascular medicine. Its management is central to the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality worldwide.[1] For decades, a vast body of evidence from Mendelian randomization studies, large prospective cohorts, and randomized controlled trials has unequivocally established a causal, dose-dependent, log-linear association between elevated concentrations of low-density lipoprotein cholesterol (LDL-C) and the risk of ASCVD events such as myocardial infarction and stroke.[1] The underlying pathophysiology involves the retention and oxidation of LDL particles within the arterial wall, initiating an inflammatory cascade that culminates in the formation of atherosclerotic plaques.[1]

This understanding has rightfully positioned LDL-C as the primary therapeutic target in dyslipidemia management, with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, serving as the first-line pharmacological intervention.[2] Statins are highly effective at lowering LDL-C and have demonstrated profound benefits in reducing cardiovascular events.[2] However, the clinical narrative does not end with LDL-C control. Even in large-scale statin trials where patients achieve significant LDL-C reduction, a substantial number of cardiovascular events still occur.[7] This phenomenon, termed "residual cardiovascular risk," has shifted scientific focus toward other components of the lipid profile that contribute to atherogenesis.