Dyslipidemia and Atherosclerotic Cardiovascular Disease: Flash Back and Vision Ahead

Abstract

Dyslipidemia is the most common modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). There is unequivocal evidence that Low Density Lipoprotein Cholesterol (LDL-C) is the main culprit. Statins, ezetimibe, bempedoic acid and Proprotein Convertase Subtilisin/ Kexin Type 9 (PCSK9) inhibitors are used to target LDL-C. Statin is always utilized as the first line therapy and they decrease LDL-C by approximately 1 mmol/l (40 mg/dL). If the LDL goals are not achieved ezetimibe is used and this decreases LDL-C by 15-20%. Bempedoic acid can also be utilized to lower LDL-C before initiating PCSK9 inhibitors but this is not available in India as yet. PCSK9 inhibitors decrease LDL-C by 1 to 1.5 mmol/l (40-60 mg/dL) on top of all lipid lowering therapy and with this very low LDL-C level targets of < 55 or even < 40 mg/dL can be achieved in very high risk patient. After the LDL-C goal is achieved, non HDL-C is targeted if the triglycerides (TG) levels are above 200 mg/dL. Targeting HDL-C with drugs is not recommended because all trials of HDL-C elevating drugs on top of statins have been negative. The role of TG has a causal factor for ASCVD is still in the process of evolution. Icospent ethyl in REDUCE IT trial has shown reduction in ischemic cardiovascular events in patients with established CVD or diabetics with other risk factors on statins and elevated TG between 135-499 mg/dL. but the mechanism of benefit does not seem to be related to lowering of TG because the benefit was similar in subgroup of patients with TG > 150 <150 mg/dL. Inclisiran which blocks the synthesis of PCSK9 is emerging as very exciting molecule for the future. It decreases LDL-C by 50% which remains there for six months after a single injection of 300 mg.