etc-1002 and Myocardial-Ischemia

Despite many improvements in its prevention and management, acute coronary syndrome (ACS) remains a major cause of morbidity and mortality in the developed world. Lipid management is an important part of secondary prevention after ACS, but many patients currently remain undertreated and do not attain guideline-recommended levels of low-density lipoprotein cholesterol reduction. This review details the current state of evidence on lipid management in patients presenting with ACS, provides directions for identification of patients who may benefit from early escalation of lipid-lowering therapy, and discusses novel lipid-lowering medication that is currently under investigation in clinical trials. Moreover, a treatment algorithm aimed at attaining guideline-recommended low-density lipoprotein cholesterol levels is proposed. Despite important advances in the initial treatment and secondary prevention of ACS, ≈20% of ACS survivors experience a subsequent ischemic cardiovascular event within 24 months, and 5-year mortality ranges from 19% to 22%. Knowledge of the current state of evidence-based lipid management after ACS is of paramount importance to improve outcomes after ACS.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Cholesterol, LDL; Cost-Benefit Analysis; Dicarboxylic Acids; Eicosapentaenoic Acid; Ezetimibe; Fatty Acids; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Lipids; Male; Middle Aged; Myocardial Ischemia; PCSK9 Inhibitors; Practice Guidelines as Topic; Risk Reduction Behavior; RNA, Small Interfering; Secondary Prevention

Lipid-lowering drugs have been shown to have cardioprotective effects but may have hidden cardiotoxic properties. Therefore, here we aimed to investigate if chronic treatment with the novel lipid-lowering drug bempedoic acid (BA) exerts hidden cardiotoxic and/or cardioprotective effects in a rat model of acute myocardial infarction (AMI). Wistar rats were orally treated with BA or its vehicle for 28 days, anesthetized and randomized to three different groups (vehicle + ischemia/reperfusion (I/R), BA + I/R, and positive control vehicle + ischemic preconditioning (IPC)) and subjected to cardiac 30 min ischemia and 120 min reperfusion. IPC was performed by 3 × 5 min I/R cycles before ischemia. Myocardial function, area at risk, infarct size and arrhythmias were analyzed. Chronic BA pretreatment did not influence cardiac function or infarct size as compared to the vehicle group, while the positive control IPC significantly reduced the infarct size. The incidence of reperfusion-induced arrhythmias was significantly reduced by BA and IPC. This is the first demonstration that BA treatment does not show cardioprotective effect although moderately reduces the incidence of reperfusion-induced arrhythmias. Furthermore, BA does not show hidden cardiotoxic effect in rats with AMI, showing its safety in the ischemic/reperfused heart.

Topics: Animals; Arrhythmias, Cardiac; Cardiotoxicity; Ischemic Preconditioning, Myocardial; Lipids; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Rats, Wistar