Keynote: Peter Libby

Peter Libby

Boston/Paris, USA/France

Dr. Peter Libby is a cardiovascular medicine specialist at Brigham and Women’s Hospital (BWH) and the Mallinckrodt Professor of Medicine at Harvard Medical School (HMS). After completing his medical degree at the University of California, San Diego School of Medicine, Dr. Libby undertook a residency in internal medicine and a fellowship in cardiovascular disease at Peter Bent Brigham Hospital (now BWH), and a research fellowship in cellular physiology at HMS. He received an honorary doctorate from the University of Lille, France. Dr. Libby is board certified in internal medicine and cardiovascular disease.

Dr. Libby’s clinical and research interests include vascular biology, atherosclerosis and preventive cardiology. His research laboratory studies the messengers created by the body that may produce arterial plaque, as well as normal and abnormal function of smooth muscle and endothelial cells. Dr. Libby discovered that vascular wall cells can produce as well as respond to pro-inflammatory cytokines. This discovery suggested autocrine and paracrine cytokine inflammatory signaling in arterial disease, and laid the groundwork for a new field in atherosclerosis research in laboratories worldwide. Dr. Libby has fostered the rapid translation to the clinic of the concepts of inflammation in arterial pathophysiology that emerged from his own laboratory work over the last twenty years. He has inspired, enabled, and participated in a number of the clinical studies that have placed inflammation at the forefront of current thinking about the diagnosis, risk stratification, and therapeutic approaches to atherosclerotic cardiovascular disease.

Dr. Libby has received numerous awards for his research accomplishments, including the Gold Medal of the European Society of Cardiology (2011), the Basic Research Prize of the American Heart Association (2011), the Anitschkow Prize in Atherosclerosis Research of the European Atherosclerosis Society (2013), the Special Award of the Heart Failure Association of the European Society of Cardiology (2014), the Ernst Jung Gold Medal for Medicine (2016), and the Earl Benditt Award from the North American Vascular Biology Organization (2017). He has received a number of lifetime achievement awards from various organizations. Dr. Libby is a Consulting Editor to Circulation Research (since 2015), and an editorial board member of Arteriosclerosis Thrombosis, and Vascular Biology.

Dr. Libby has published extensively in numerous high impact journals including Circulation, Journal of Clinical Investigation, Proceedings of the National Academy of Sciences, New England Journal of Medicine, and Nature. He is an Editor of Braunwald’s Heart Disease, having served as the Editor-in Chief of the 8th Edition, and has also contributed chapters on the pathogenesis, treatment, and prevention of atherosclerosis to many editions of Harrison’s Principles of Internal Medicine. Dr. Libby has held numerous visiting professorships and delivered more than 100 major named or keynote lectures throughout the world.

 

 


Anti-inflammatory therapy and resolution of inflammation, theory and practice

Inflammation plays a key role in all stages of the atherothrombotic process, and it has long been recognized that subclinical inflammation is a predictor of future cardiovascular events. Vascular biology research has also provided important insights into the inflammatory pathways mediating atherothrombosis, and identified potential targets for therapeutic intervention. Thus, accumulating evidence has provided a rationale for testing whether drugs that primarily target inflammation can reduce cardiovascular events. In particular, one mediator – interleukin-1β (IL-1β), a proinflammatory cytokine that has multiple roles in the atherothrombotic process –attracted interest as a focus for therapeutic intervention.

In 2017, there was the first evidence from a prospective outcomes study that targeting inflammation reduced cardiovascular events in high risk patients. The agent tested in this trial was canakinumab, a high affinity monoclonal antibody that specifically targets IL-1β. The trial was very much ‘proof-of-concept’ in that the trial population was well treated with intensive statin therapy with low-density lipoprotein cholesterol (LDL-C) levels at baseline lower than those observed in the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial. CANTOS showed a significant reduction in the primary ‘hard outcomes’ endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death, with evidence of a dose-response for canakinumab, and greater clinical benefit in patients with higher levels of inflammation. Incidentally, canakinumab had effects beyond reduction in cardiovascular outcomes, specifically a reduction in cancer mortality, which is consistent with mechanistic and observational findings linking inflammation and cancer.

CANTOS has therefore provided the foundation for a new era for anti-inflammatory therapies for atherothrombosis. It is, however, recognized that not all patients will present with this inflammatory profile. From the clinician’s perspective, such insights offer the possibility of personalizing the management of high risk patients in accordance with their risk factor profile, thus enabling judicious and appropriate use of healthcare resources.

Key references

Libby P. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond. J Am Coll Cardiol 2017;70:2278-89.

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31.

Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ; CANTOS Trial Group. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 2017;390:1833-42.

Libby P, Nahrendorf M, Swirski FK. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “Cardiovascular Continuum”. J Am Coll Cardiol 2016;67:1091-103.