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Comparison of Early Surgical or Transcatheter Aortic Valve Replacement Versus Conservative Management in Low-Flow, Low-Gradient Aortic Stenosis Using Inverse Probability of Treatment Weighting: Results From the TOPAS Prospective Observational Cohort Study Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry Thrombotic Versus Bleeding Risk After Transcatheter Aortic Valve Replacement: JACC Review Topic of the Week Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study Intravascular Ultrasound Guidance vs. Angiographic Guidance in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction - Long-Term Clinical Outcomes From the CREDO-Kyoto AMI Registry Right ventricular function and outcome in patients undergoing transcatheter aortic valve replacement Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials Regurgitant Volume/Left Ventricular End-Diastolic Volume Ratio: Prognostic Value in Patients With Secondary Mitral Regurgitation The Science Underlying COVID-19: Implications for the Cardiovascular System

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.