Statins

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors that have been used for 30 years to prevent coronary artery disease and stroke. ^[1] Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. ^[2] Statins are recommended as first-line therapy for primary and secondary cardiovascular prevention in patients with hypercholesterolaemia and hypertriglyceridaemia. ^[3]

The primary mechanism of action of statins is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis, thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. ^[1] Statins may also exert cardiovascular protective pleiotropic effects that are independent of LDL-cholesterol lowering, including altered expression of endothelial nitric oxide synthase, stabilization of atherosclerotic plaques, and reduced production of proinflammatory cytokines and reactive oxygen species. ^[1]

In a prospective meta-analysis of 90,056 participants in 14 randomised trials, there was a 12% proportional reduction in all-cause mortality and a 21% reduction in any major vascular event per 1.0 mmol/L reduction in LDL cholesterol. ^[4] In people with no history of cardiovascular disease, statins reduced all-cause mortality and combined fatal and non-fatal cardiovascular disease, with no evidence of any serious harm caused by statin prescription in that primary-prevention review. ^[5] In geroscience, statins are cholesterol-lowering medications used to prevent development and progression of atherosclerosis, but such disease-focused treatments do not alter aging's effects, and statins do not significantly reduce noncardiovascular mortality or cancer. ^[6]

Statin-associated myopathy, with significant elevation of serum creatine kinase, is a rare but serious side effect affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. ^[7] The risk of statin-induced serious muscle injury, including rhabdomyolysis, is less than 0.1%, the risk of serious hepatotoxicity is about 0.001%, and the risk of statin-induced newly diagnosed diabetes mellitus is about 0.2% per year of treatment. ^[8] Statins cause a moderate dose-dependent increase in new diagnoses of diabetes, with low-intensity or moderate-intensity statin therapy resulting in a 10% proportional increase and high-intensity statin therapy resulting in a 36% proportional increase in new-onset diabetes compared with placebo. ^[9] Placebo-controlled randomised trials have shown that almost all of the symptomatic adverse events attributed to statin therapy in routine practice are not actually caused by it, and the only serious adverse events shown to be caused by long-term statin therapy are myopathy, new-onset diabetes mellitus, and probably haemorrhagic stroke. ^[10]