Marc S. Sabatine, MD, MPH is the Chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group, an Associate Physician in Cardiovascular Medicine at Brigham and Women’s Hospital (BWH), and an Associate Professor of Medicine at Harvard Medical School. After completing his medical degree at Harvard Medical School, Dr. Sabatine undertook a clinical fellowship in cardiovascular disease at Massachusetts General Hospital and a fellowship in cardiovascular research at BWH. His clinical interest is in acute coronary syndromes and critical care, and his research interests include coronary artery disease, acute coronary syndromes, dyslipidaemias, proteomics and genomics. As chairman of the TIMI Study Group—an academic research organization that has led major cardiovascular medicine clinical trials since its inception in 1984—Dr. Sabatine leads large-scale international randomized controlled trials testing novel therapies for cardiovascular care that have shaped the practice of medicine. Dr. Sabatine is a fellow of the American Heart Association, the American College of Cardiology and the European Society of Cardiology.
Wednesday 29 May 10:00
New lipid drugs: Is LDL done, ready for new targets?
Low-density lipoprotein (LDL) is indisputably causal for cardiovascular disease. The first of the statin trials, the Scandinavian Simvastatin Survival Study (4S) established the cardiovascular benefit of LDL cholesterol lowering in patients with known vascular disease; subsequent trials with statin monotherapy, and the combination of statin plus ezetimibe, have supported a ‘lower is better’ strategy. Added to this, epidemiological studies in non-Western native populations show that lower LDL cholesterol levels are effective in preventing atherosclerotic cardiovascular disease and are safe.
Most recently, genetic insights into proprotein convertase subtilisin kexin type 9 (PCSK9) paved the way for a novel class of therapeutics: the PCSK9 inhibitors. These treatments have been shown to be highly efficacious in lowering LDL cholesterol, reducing cardiovascular events and, to date, are safe over the duration of clinical trials. Moreover, there is no evidence to suggest any threshold in LDL cholesterol lowering for clinical benefit. The key question, therefore, is whether the availability of PCSK9 inhibitors represents the ‘holy grail’ for LDL lowering therapy?
Atherosclerosis is undoubtedly a multifactorial disease in which chronic inflammation plays a key role. Investigators have now turned their attention to consider other targets that contribute to residual risk that persists even at very low LDL cholesterol. Findings from the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) supported the relevance of inflammatory risk, although the search for other novel targets will undoubtedly continue.
Sabatine MS, Wiviott SD, Im K, Murphy SA, Giugliano RP. Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: a meta-analysis. JAMA Cardiol 2018. doi: 10.1001/jamacardio.2018.2258. [Epub ahead of print]
Giugliano RP, Keech A, Murphy SA, Huber K, Tokgozoglu SL, Lewis BS, Ferreira J, Pineda AL, Somaratne R, Sever PS, Pedersen TR, Sabatine MS. Clinical efficacy and safety of evolocumab in high-risk patients receiving a statin: secondary analysis of patients with low LDL cholesterol levels and in those already receiving a maximal-potency statin in a randomized clinical trial. JAMA Cardiol 2017;2:1385-91.
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22.