Key result
Anti-inflammatory therapies for atherosclerosis demand precise human targets following lessons from CANTOS and CIRT.
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This review synthesizes the evidence on targeting inflammation in atherosclerosis, analyzing the implications of the CANTOS and CIRT trials for future immune-modulatory therapies.
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-Inflammatory Thrombosis 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.
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Zhao et al. (2019) conducted a review in Atherosclerosis. Anti-inflammatory therapies was evaluated. Anti-inflammatory therapies for atherosclerosis are reviewed, highlighting lessons from CANTOS and CIRT, potential hazards, and the need for human model organisms to identify appropriate targets.
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