A Comprehensive Review of PCSK9 Inhibitors.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk. With the discovery of PCSK9 inhibitors, the ability to provide more aggressive treatment for patients with homozygous and heterozygous familial hypercholesterolemia has increased. Ezetimibe reduces LDL-C by 15%-20% when combined with statin.2,3 Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to achieve profound reductions in LDL-C (54%-74%) when added to statins. They have shown dramatic effects at lowering major adverse cardiovascular events (MACE) in high-risk patients4 with LDL-C levels ≥70 mg/dL and can be used in populations that are statin intolerant or not at goal levels with maximally tolerated statin therapy. PCSK9 inhibitors also produce minimal side effects. Myopathy, a common side effect for patients on statins, has been rare in patients on PCSK9 inhibitors. Randomized trials have shown that reduction in LDL-C has translated to clinical benefits even in patients who have not achieved their LDL-C target.

State of the Art Comprehensive Review of Individual Statins, Their Differences, Pharmacology, and Clinical Implications.

Statins are currently the primary treatment for hyperlipidemia, particularly for the treatment of high levels of low-density lipoprotein cholesterol (LDL-C), as many studies have proven benefit in a variety of populations. The benefits of statin treatment for high cholesterol have been proven in many trials. Forefront among different adverse events is statin-induced myopathy, which still eludes complete understanding, and may range anywhere from muscle soreness or fatigue to potentially extremely rare occurrence of rhabdomyolysis.As most adverse events are rare and not life-threatening, in high-risk patients, a high-dose statin should be started initially as data suggests that clinicians rarely up titrate statin therapy after initial prescription leading to under-treatment of many patients requiring high-dose statin therapy. As we will discuss in this paper, musculoskeletal side effects are the main concern and reason for discontinuing statin therapy. The occurrence and true association of other adverse events in patients on statin such as new onset of diabetes, hepatic toxicity, or cognitive impairment are rare, controversial, and not proven. In placebo-controlled studies, abnormal liver function occurs to a similar degree in statin- and placebo-treated patients. This led to FDA removal of the requirement to monitor liver function tests in patients on statin therapy.The combination of statins with other compounds such as ezetimibe or PCSK9 inhibitors has shown some additional benefits in the treatment of hypercholesterolemia. The goal of this manuscript is to conduct a comprehensive review about most commonly used statins and compare data on their history, structures, benefits, adverse effects, and clinical outcomes.