Statins plus ezetimibe in the era of proprotein convertase subtilisin/ kexin type 9 inhibitors

Statins are first‑line agents used in patients with dyslipidemia, which show established benefits in reducing low‑density lipoprotein cholesterol (LDL‑C) levels and decreasing the rate of cardiovascular events. However, a considerable number of patients on statins do not achieve target LDL‑C levels, even at maximally tolerated statin doses, or are intolerant to intensive statin therapy. These patients can benefit from the addition of a nonstatin lipid‑lowering agent, and recent cholesterol guidelines have put greater focus on combination lipid‑lowering therapy. In patients who cannot achieve target treatment goals with statin therapy alone, the addition of a cholesterol absorption inhibitor, ezetimibe, leads to further LDL‑C reduction with good tolerability and decreases cardiovascular morbidity and mortality. The more recent proprotein convertase subtilisin‑like / kexin type 9 (PCSK‑9) inhibitors can lower LDL‑C by additional 45% to 65% and are also well tolerated. These complementary approaches for LDL‑C lowering in patients treated with statins decrease LDL‑C levels more effectively than statin monotherapy. As no threshold level has been established below which LDL‑C lowering benefits disappear, the early application of a combination treatment strategy may lead to improved cardiovascular outcomes, particularly in high‑risk patients. This review examines the rationale, advantages, and potential barriers to combination lipid‑lowering therapy with reference to the current guideline recommendations