Lipid lowering combination therapy: From prevention to atherosclerosis plaque treatment

Statins have contributed to the prevention of numerous atherosclerotic cardiovascular (CV) events and cardio-vascular deaths in the past three decades. The benefit of statins is mainly mediated by the lowering of LDLc. According to scientific evidence, the current international guidelines recommend very low LDLc goals in patients at high/very high cardiovascular risk because they are associated with fewer CV events and improvements in atherosclerotic plaques. However, these goals often cannot be obtained with statins alone. Recent RCTs have demonstrated that these CV benefits can also be obtained with nonstatin LDLc-lowering drugs such as PCSK9 inhibitors (alirocumab and evolocumab), ezetimibe and bempedoic acid, while evidence with inclisiran is up-coming. Icosapent ethyl, a lipid metabolism modifier, has also shown an effect on event reduction. Physicians should take advantage of the currently available lipid-lowering therapies, choosing the drug or combination of drugs that is most appropriate for each patient according to his or her CV risk and baseline LDLc concentration. Strategies implementing combination therapies from early stages or even from the outset may increase the number of patients attaining LDLc goals, thereby preventing new CV episodes and improving existing athero-sclerotic lesions.

Automated summary

Statins have played a significant role in preventing atherosclerotic cardiovascular events and deaths by reducing LDL cholesterol levels. International guidelines recommend low LDL cholesterol goals for patients at high cardiovascular risk. However, these goals may not be attainable with statins alone. Recent trials have shown that nonstatin drugs like PCSK9 inhibitors, ezetimibe, bempedoic acid, and icosapent ethyl can also provide cardiovascular benefits. Physicians should use combination therapies based on a patient's risk and LDL cholesterol levels to achieve LDL cholesterol goals and improve cardiovascular outcomes.