Safety Issues Associated With the Clinical Application of PCSK9 Inhibitors: Current Findings

Reduction in low-density lipoprotein cholesterol levels is the cornerstone of treatment and prevention of atherosclerotic cardiovascular diseases. Currently, high-intensity statins are being used as the first-line therapy to lower low-density lipoprotein cholesterol levels, as they improve the prognosis of patients with atherosclerotic cardiovascular disease and those in high-risk groups. However, in some patients, the expected reduction in cholesterol is not achieved despite aggressive treatment with statins. Moreover, some patients cannot tolerate the dosage or show poor response or compliance to statins. Therefore, combination therapies with statins and other medications should be considered. Recently, several clinical trials have shown that the use of proprotein convertase subtilisin/kexin type 9 inhibitors with or without statins and/or other lipid-lowering drugs can significantly reduce low-density lipoprotein cholesterol levels, sometimes to extremely low levels. Therefore, to facilitate appropriate prescription of these new lipid-lowering drugs, we systemically evaluated the safety issues associated with these inhibitors and extremely low low-density lipoprotein cholesterol levels.