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.