In 2015 the U.S. Food and Drug Administration approved the first two proprotein 
convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab (Praluent®; 
Sanofi/ Regeneron) and evolocumab (Repatha®; Amgen), for use in patients with 
heterozygous and homozygous familial hypercholesterolemia and for patients 
intolerant of statins or those with a major risk of cardiovascular disease (CVD) 
but unable to lower their LDL cholesterol (LDL-C) to optimal levels with statins 
and ezetimibe. Numerous randomized clinical trials have demonstrated that these 
inhibitors cause a fall in LDL-C levels of 50-60% as well as causing a decline 
in lipoprotein(a) and an increase in HDL cholesterol. They are effective in 
reducing levels of LDL-C to 1.8 mmol/L or less in almost all patients in the 
groups listed above except for those with homozygous familial 
hypercholesterolemia. In the latter case, many patients will still have LDL-C 
levels well above optimal levels despite the use of statins and a PCSK9 
inhibitor. To date these inhibitors have not caused major adverse effects. 
However, the results of ongoing long-term randomized clinical trials are needed 
to determine whether they cause a significant reduction in CVD events including 
deaths from CVD. These studies will also demonstrate whether the PCSK9 
inhibitors have any unexpected adverse effects and/or effects resulting from the 
loss of PCSK9 functions at other sites in the body, in particular regarding 
neurocognition. A further major concern is the high cost of PCSK9 inhibitors and 
their effect on healthcare costs and health insurance premiums.