Bempedoic Acid in PPCI Impact on Clinical Outcome and Inflammatory Markers

ST Elevation (STEMI) Myocardial Infarction

Bempedoic acid, TNF alpha, PPCI

Bempedoic acid in PPCI

Cardiovascular disease persists as the predominant cause of global burden of mortality and morbidity worldwide(1). The cholesterol hypothesis posits that elevated blood cholesterol levels constitute a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) and reducing cholesterol levels will consequently lower the risk of ASCVD(2). Treatments aimed at lowering lipid levels have demonstrated their effectiveness in decelerating the advancement of atherosclerotic disease(3). This finding further reinforces the pathophysiological connections between plasma lipids and the progression of CAD. Among non-lipid mechanisms involved in reducing CAD progression, lipid-lowering drugs have also been implicated in plaque stabilization, reduced inflammation, reversal of endothelial dysfunction, and decreased thrombogenicity(3). It is widely accepted that the beneficial effects of statins on cardiovascular events are mainly linked to their cholesterol lowering properties. Nonetheless, statins also have a clear action in reducing systemic inflammation. The effect on hsCRP is proportionally similar to that on LDL-C(4). It is known that an anti-inflammatory action contributes to the reduction of cardiovascular risk independently of the effect on LDL-C. Four-year therapy with canakinumab, a specific anti-interleukin-1b monoclonal antibody, in patients with previous myocardial infarction reduced the relative risk of relapse by approximately 15% by reducing hsCRP levels by 60% without modifying LDL-C(5). It is therefore possible to hypothesize that cholesterol lowering drugs with an effect on hsCRP, such as statins and bempedoic acid, have advantages in reducing cardiovascular events compared to those that do not act on inflammation, such as PCSK9 inhibitors(4). Bempedoic acid is a new cholesterol-lowering drug, which has recently received US FDA approval. It offers a safe and effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins or in addition to statins in patients who are not reaching the LDL target(6). Bempedoic acid targets lipid and glucose metabolism as well as inflammation. The primary effect is the reduction of cholesterol synthesis in the liver and its administration is generally not associated to unwanted muscle effects(4). Bempedoic acid may decrease gluconeogenesis leading to improved insulin sensitivity, glucose metabolism, and metabolic syndrome(4). The anti-inflammatory action of bempedoic acid is mainly achieved via activation of AMPK pathway in the immune cells, leading to decreased plasma levels of C-reactive protein(4). However, its potential role in modulating post-PCI inflammatory response has not been fully investigated, especially in primary PCI setting.

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