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Atherothrombosis Prevention and Treatment with Anti-interleukin-1 Agents

  • Giuseppe Biondi-ZoccaiEmail author
  • Cristian M. Garmendia
  • Antonio Abbate
  • Arturo Giordano
  • Giacomo Frati
  • Sebastiano Sciarretta
  • Barbara Antonazzo
  • Francesco Versaci
Evidence-Based Medicine, Clinical Trials and Their Interpretations (L. Roever, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Evidence-Based Medicine, Clinical Trials and Their Interpretations

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.

Keywords

Anakinra Anti-interleukin-1 agent Atherosclerosis Atherothrombosis Canakinumab Heart failure Interleukin-1 Peripheral artery disease Stroke 

Notes

Compliance with Ethical Standards

Conflict of Interest

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.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Guarantor

G.B.Z. is the guarantor of this manuscript.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Giuseppe Biondi-Zoccai
    • 1
    • 2
    Email author
  • Cristian M. Garmendia
    • 3
  • Antonio Abbate
    • 3
  • Arturo Giordano
    • 4
  • Giacomo Frati
    • 1
    • 5
  • Sebastiano Sciarretta
    • 1
    • 5
  • Barbara Antonazzo
    • 6
  • Francesco Versaci
    • 7
  1. 1.Department of Medico-Surgical Sciences and BiotechnologiesSapienza University of RomeLatinaItaly
  2. 2.Mediterranea CardiocentroNaplesItaly
  3. 3.Pauley Heart Center, Department of Internal MedicineVirginia Commonwealth UniversityRichmondUSA
  4. 4.Unità Operativa di Interventistica CardiovascolarePresidio Ospedaliero Pineta GrandeCastel VolturnoItaly
  5. 5.IRCCS NEUROMEDPozzilliItaly
  6. 6.Division of GeriatricsIsraelite HospitalRomeItaly
  7. 7.Unità Operativa Complessa di CardiologiaOspedale Santa Maria GorettiLatinaItaly

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