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Comparison of paclitaxel-eluting stents (Taxus) and everolimus-eluting stents (Xience) in left main coronary artery disease with 3 years follow-up (from the ESTROFA-LM registry) Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure Permanent pacemaker use among patients with heart failure and preserved ejection fraction: Findings from the Acute Decompensated Heart Failure National Registry (ADHERE) National Registry Clinical applications of machine learning in the diagnosis, classification, and prediction of heart failure Intravascular Ultrasound-Guided Versus Angiography-Guided Implantation of Drug-Eluting Stent in All-Comers: The ULTIMATE trial Long-Term Durability of Transcatheter Heart Valves: Insights From Bench Testing to 25 Years Combined Tricuspid and Mitral Versus Isolated Mitral Valve Repair for Severe MR and TR: An Analysis From the TriValve and TRAMI Registries Metabolic Interactions and Differences between Coronary Heart Disease and Diabetes Mellitus: A Pilot Study on Biomarker Determination and Pathogenesis Rationale and design of a randomized clinical trial comparing safety and efficacy of Myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: the LANDMARK trial Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure

Review ArticleVolume 73, Issue 13, 9 April 2019, Pages 1691-1706

JOURNAL:J Am Coll Cardiol. Article Link

Targeting the Immune System in Atherosclerosis: JACC State-of-the-Art Review

TX Zhao, Z Mallat. Keywords: atherosclerosis; clinical trials; immune system; inflammation; therapy and outcome

ABSTRACT


Atherosclerosis has long been known as an inflammatory disease. However, whether targeting inflammation improves outcomes was unproven until the recent results of CANTOS (Canakinumab Anti-InflammatoryThrombosis Outcomes Study). In this review, we reflect on why it has taken a long time to prove the inflammatory hypothesis of atherosclerosis and derive important lessons for the future. In particular, we discuss the off-target immune-modulatory effects of approved cardiovascular therapies, review the attempted anti-inflammatory therapies including the recently published CIRT (Cardiovascular Inflammation Reduction Trial), and discuss the likely reasons for their failures. We further build on CANTOS to review the immune-modulatory therapies for atherosclerosis currently in trials, and discuss the likelihood of their added value as well as the potential hazard associated with their use. We finally argue for a critical approach to the use of animal models, coupled with the use of humans as model organisms to accelerate the identification of the most appropriate targets.