PCSK9 inhibition in high-risk patients

advancing age, resulting in high mortality and morbidity worldwide. As societies continue to age, >80% of individuals dying from CVD are 65 years or older. Main reason for increased CVD in older people is an absolute increase in atherosclerotic plaque burden. [1] Patients with high plaque burden often have highest clinical benefit from cardiovascular treatment: because absolute risk is high, absolute risk reductions are also relatively high. Therefore, it remains a key point to identify these the subsets of patients with highest plaque burden to provide an optimal treatment strategy with high benefit but low risk. Measuring total plaque burden could provide the most accurate risk stratification. But although various imaging techniques exist, none are currently suitable to implement in routine daily practice. Therefore, surrogate markers of plaque burden should be used, as low-density lipoprotein cholesterol (LDLC). In addition, patients can be classified according to clinical features that also reflect plaque burden, which provides an easy and cost-effective manner to achieve optimal treatment. Well-known clinical high risk features include patients with chronic kidney disease or diabetes, and also patients with known vascular disease such as a history of coronary artery bypass grafting (CABG) or atherosclerosis in multiple vascular beds (polyvascular disease). Relatively frail patients are more prone to side effects of treatment, for instance due to an increased bleeding risk. Therefore, finding treatment for primary or secondary prevention with high benefit but low risk of adverse effects is important, especially in older patients. Standard cardiovascular treatment options include medication as aspirin or specific oral anticoagulants, beta-blockers, antihypertensives and lipid-lowering, next to life-style modification, e.g. smoking cessation and regular exercise. Lipid-lowering provides plaque stability and is relatively safe, as the most clinically relevant adverse effect of statins is myopathy. However, especially in older patients statin-associated muscle symptoms can be problematic in daily life. The available evidence from trials indicates that statin therapy produces significant reductions in major adverse cardiovascular events (MACE) irrespective of age, although evidence indicates there is no benefit among patients aged >75 years who do not already have evidence of occlusive vascular disease. Accordingly, Editorial