Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin.

Pathophysiological, epidemiological, and genetic studies provide strong evidence that lipoprotein(a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). Specific therapies to address Lp(a)-mediated CVD and CAVD are in clinical development. Due to knowledge gaps, the National Heart, Lung, and Blood Institute organized a working group that identified challenges in fully understanding the role of Lp(a) in CVD/CAVD. These included the lack of research funding, inadequate experimental models, lack of globally standardized Lp(a) assays, and inadequate understanding of the mechanisms underlying current drug therapies on Lp(a) levels. Specific recommendations were provided to facilitate basic, mechanistic, preclinical, and clinical research on Lp(a); foster collaborative research and resource sharing; leverage expertise of different groups and centers with complementary skills; and use existing National Heart, Lung, and Blood Institute resources. Concerted efforts to understand Lp(a) pathophysiology, together with diagnostic and therapeutic advances, are required to reduce Lp(a)-mediated risk of CVD and CAVD.

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Familial hypercholesterolaemia is common in individuals who had a myocardial infarction at a young age. As many as one in 200 people could have heterozygous familial hypercholesterolaemia, and up to one in 300 000 individuals could be homozygous. The phenotypes of heterozygous and homozygous familial hypercholesterolaemia overlap considerably; the response to treatment is also heterogeneous. In this Review, we aim to define a phenotype for severe familial hypercholesterolaemia and identify people at highest risk for cardiovascular disease, based on the concentration of LDL cholesterol in blood and individuals' responsiveness to conventional lipid-lowering treatment. We assess the importance of molecular characterisation and define the role of other cardiovascular risk factors and advanced subclinical coronary atherosclerosis in risk stratification. Individuals with severe familial hypercholesterolaemia might benefit in particular from early and more aggressive cholesterol-lowering treatment (eg, with PCSK9 inhibitors). In addition to better tailored therapy, more precise characterisation of individuals with severe familial hypercholesterolaemia could improve resource use

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis.

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Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10–15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.

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