Statins. The Great Age and beyond Biologically LDL Level, Revisited Forty Years Later

The LDLR and its mutations were described, determinants of the FH phenotype in 1974, at the same time, the first statin (compactin) with hypocholesterolemic affect was discovered in 1976. Statins, by inhibiting HMGCoAR and blocking the cellular synthesis of cholesterol, induce its main therapeutic effect, namely: the activation of the synthesis, expression and function of LDLR and with it, a greater hepatic clearance of LDL and lower blood cholesterol level. Statins also reduce the synthesis of VLDL and have non-lipid or pleiotropic effects. The canonical meta-analysis of CTT with one hundred and seventy thousand individuals treated with statins in twenty-six RCT and their “patient by patient” analyses, allow us to establish the following therapeutic postulate: reduction of 40, 80 and 120 mg/dL of LDL-cholesterol with a statin results in a 20%, 40% and 50% risk reduction of an ASCVD. A significant benefit without a doubt. This therapeutic benefit with statins has been the “master key” for all groups of experts in Lipidology and Cardiology to consider this pharmacological group as the gold standard in the prevention of ASCVD. All Guidelines for hypercholesterolemia treatment and prevention of ASCVD contemplate the following three fundamental concepts: LDL-cholesterol is the main atherogenic risk factor and therapeutic target. Estimating the absolute 10-year cardiovascular risk is our best tactic to guide the therapeutic strategy. Up today, statins are our best therapeutic strategy for controlling hypercholesterolemia and preventing ASCVD. In the PCSK9 inhibition era and before the first CVOT with MAbs-PCSK9 publication, this paper reviews briefly the amazing statin's history since Endo, Goldstein and Brown´s discoveries until their solid and evidence-based position in all guidelines devoted to hypercholesterolemia and ASCVD risk reduction.