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Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study Comparison of Accuracy of One-Use Methods for Calculating Fractional Flow Reserve by Intravascular Optical Coherence Tomography to That Determined by the Pressure-Wire Method Impact of percutaneous coronary intervention extent, complexity and platelet reactivity on outcomes after drug-eluting stent implantation Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome: A Pilot Randomized Controlled Trial Pulmonary Artery Pressure-Guided Management of Patients With Heart Failure and Reduced Ejection Fraction Outcome of Applying the ESC 0/1-hour Algorithm in Patients With Suspected Myocardial Infarction Novel functions of macrophages in the heart: insights into electrical conduction, stress, and diastolic dysfunction Incidence, predictors, and outcomes of DAPT disruption due to non-compliance vs. bleeding after PCI: insights from the PARIS Registry Hs-cTroponins for the prediction of recurrent cardiovascular events in patients with established CHD - A comparative analysis from the KAROLA study

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.