ABSTRACT
Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence.
ABSTRACT
The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach 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. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. 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.
