Key Points
• Source: Biomedicines
• Conclusion: “In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of “the lower, the better”, we also discuss the concept of “the earlier, the better”, which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.”
• A mainstay of the secondary prevention of atherosclerotic disease progression is the swift decrease of circulating low-density lipoprotein cholesterol (LDL-C). Although statins and ezetimibe drop lipid levels, many very-high-risk patients with cardiovascular disease do not attain the recommended treatment goal of <55 mg/dL (<1.4 mmol/L).
• “Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents,” the authors wrote. “These innovative therapies have demonstrated promising results in clinical studies.”
• Current guidelines indicate stepwise intensification of lipid-lowering therapy during 4–6 weeks. Even with an early start with a lipid-lowering triple therapy (Statin + ezetimibe + PCSK9 inhibition), however, attaining LDL-C goals can take up to 3 months. This lag could increase the risk of recurrent myocardial infarction, which is highest in the early phase after an index event.
• Bempedoic acid has a good safety profile. Unlike statins, this agent does not seem to cause myopathy, which could be due to the necessity of activation in the liver cells by the enzyme ACSVL1, which is not present in skeletal muscles. Higher levels of uric acid, however, were noted in a small minority of patients taking bempedoic acid (1%–2%)