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Atherothrombosis Prevention and Treatment with Anti-interleukin-1 Agents

  • Evidence-Based Medicine, Clinical Trials and Their Interpretations (L. Roever, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

A Correction to this article was published on 29 January 2020

This article has been updated

Abstract

Purpose of Review

Despite major advances in terms of prevention, diagnosis, risk-stratification, management and rehabilitation, atherosclerosis and atherothrombosis continue to have major morbidity and mortality implications worldwide. Since the unraveling of the pivotal role of inflammation in atherothrombosis pathophysiology, several focused treatments have been proposed with the ultimate goal of preventing or treating myocardial infarction, stroke, and peripheral artery disease. In particular, given the centrality of interleukin-1 (IL-1), targeted anti-IL-1 agents have attracted substantial attention and efforts. Yet, uncertainty persists on the real risk-benefit and cost-benefit balance of anti-IL-1 agents in patients with or at risk of atherothrombosis.

Recent Findings

Several trials have been recently completed on atherothrombosis prevention and treatment with anti-IL-1 agents, ranging, for instance, from the large Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial to the series of translational studies conducted within the Virginia Commonwealth University-Anakinra Remodeling Trial (VCU-ART) platform. In light of the present scoping umbrella review, it appears evident that anti-IL-1 agents can reduce systemic inflammation and improve surrogate markers of cardiac and vascular function, with potential benefits on the risk of new/worsening heart failure. One trial suggested an increased risk of major adverse events with anti-interleukin-1 agents, possibly due to a rebound phenomenon, but this was based on a post-hoc analysis of a small number of events, and it was not supported by all other pertinent trials. The CANTOS study showed a potential hazard due to an increased risk of fatal infections, but the effect size was rather small. In addition, cost issues limit the foreseeable scope of these treatment strategies in unselected patients, calling instead for more refined prescribing.

Summary

The evidence base on the risk-benefit and cost-benefit profile of anti-IL-1 agents for atherothrombosis prevention and treatment has expanded substantially in the last decade. While largely dominated by the landmark CANTOS trial, effect estimates also including the VCU-ART trials suggest complex short- and long-term effects which may prove favorable in carefully selected patients with acute or chronically sustained inflammation. Conversely, more liberal use appears less promising, and further studies with currently available agents or novel ones are eagerly needed to better define their role in the era of precision molecular medicine.

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Change history

  • 29 January 2020

    The original version of this article unfortunately contained typo in the 2nd author’s family name. Instead of “Garmenda”, it should be “Garmendia”. The original version has been corrected.

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Authors and Affiliations

  1. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100, Latina, Italy

    Giuseppe Biondi-Zoccai, Giacomo Frati & Sebastiano Sciarretta

  2. Mediterranea Cardiocentro, Naples, Italy

    Giuseppe Biondi-Zoccai

  3. Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA

    Cristian M. Garmendia & Antonio Abbate

  4. Unità Operativa di Interventistica Cardiovascolare, Presidio Ospedaliero Pineta Grande, Castel Volturno, Italy

    Arturo Giordano

  5. IRCCS NEUROMED, Pozzilli, Italy

    Giacomo Frati & Sebastiano Sciarretta

  6. Division of Geriatrics, Israelite Hospital, Rome, Italy

    Barbara Antonazzo

  7. Unità Operativa Complessa di Cardiologia, Ospedale Santa Maria Goretti, Latina, Italy

    Francesco Versaci

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  1. Giuseppe Biondi-Zoccai
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  2. Cristian M. Garmendia
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Correspondence to Giuseppe Biondi-Zoccai.

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Giuseppe Biondi-Zoccai, Cristian M. Garmendia, Arturo Giordano, Giacomo Frati, Sebastiano Sciarretta, Barbara Antonazzo, and Francesco Versaci declare that they have no conflict of interest. Antonio Abbate reports grants and personal fees from Kiniksa, Novartis, Olatec, and Swedish Orphan Biovitrum outside the submitted work.

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Biondi-Zoccai, G., Garmendia, C.M., Abbate, A. et al. Atherothrombosis Prevention and Treatment with Anti-interleukin-1 Agents. Curr Atheroscler Rep 22, 4 (2020). https://doi.org/10.1007/s11883-020-0819-1

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