Atherosclerosis and Lipid Lowering: is there a Need for New Agents?

Cardiovascular disease (CVD) is the leading cause of death worldwide. Among well-known risk factors, such as visceral obesity, sedentary lifestyle, metabolic syndrome, smoking, hypertension, age, gender, family history of heart attacks, diabetes, low levels HDL-C, high levels of LDL-C and total cholesterol are very strong predictors of CVD events and death.In recent years, there have been significant advances in the elucidation of biomarkers of atherosclerotic disease, and also their pathogenesis, prevention and treatment. Atherosclerosis is a systemic inflammatory disease characterized by on-going progression in response to systemic risk factors and local pro-atherogenic stimuli that leads to acute myocardial infarction, stroke and lower limb ischemia. 

Statins has substantially reduced CVD events around the world and is recommended as first-line therapy for CVD management. However, a need for other lipid-loweringagents, because some patients do not tolerate statins due to adverse events, or cannot reach LDL-C level desired because of high levels of LDL-C, or patients with very high risk cardiovascular events need more intensive reduction therapy. Can we pay the benefits of these new agents when statins are effective and inexpensive?

Zhang et al. reported a meta-analysis study to evaluate the safety and efficacy of anti-PCSK9 antibodies in randomized, controlled trials (RCTs). Twenty-five RCTs encompassing 12,200 patients were included. The study showing largely no significant difference between anti-PCSK9 antibodies and placebo (or ezetimibe), except that alirocumab was associated with reduced rates of death (relative risk (RR): 0.43, 95 % CI: 0.19 to 0.96, P =0.04) and an increased rate of injection-site reactions (RR: 1.48, 95 % CI: 1.05 to 2.09, P =0.02); evolocumab reduced the rate of abnormal liver function (RR: 0.43, 95 % CI: 0.20 to 0.93, P =0.03), both compared with placebo. Evolocumab and alirocumab substantially reduced the LDL-C level by over 50%, increased the HDL-C level, and resulted in favourable changes in other lipids. Read more.............