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Targeting Inflammation to Reduce Residual Cardiovascular Risk

  • Nonstatin Drugs (M. Vrablik, Section Editor)
  • Published:
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Abstract

Purpose of Review

Patients with established cardiovascular disease are at high risk for recurrent myocardial infarction, stroke, and cardiovascular death. The term residual risk refers to this risk that persists, even after optimal treatment. Considerable progress has been made to understand the biological basis of residual risk and to devise therapies that can safely and effectively reduce risk. The presence of ongoing subclinical vascular inflammation is known to be a marker of elevated residual risk, and reductions in measures of vascular inflammation predict improved outcome in these patients.

Recent Findings

Recent trials of anti-inflammatory agents have specifically tested the hypothesis that inflammation reduction reduces residual cardiovascular risk. Most prominent among these are the CANTOS, COLCOT, and CIRT trials. CANTOS enrolled patients with prior myocardial infarction (MI) and a high-sensitivity C-reactive protein ≥ 2 mg/L and reported a 15% reduction in major adverse cardiovascular events (MACE; HR 0.85, 95% CI 0.74–0.98) with the interleukin-1β inhibitor canakinumab. In COLCOT, colchicine 0.5 mg daily led to a 23% relative risk reduction (HR 0.77, 95% CI 0.61–0.96) in major vascular events in patients with recent acute coronary syndrome. By contrast, CIRT was stopped early for lack of benefit of low-dose methotrexate in preventing MACE in patients with coronary artery disease and either type 2 diabetes or the metabolic syndrome.

Summary

Ongoing subclinical inflammation is an important marker of risk in patients with established cardiovascular disease, and novel therapies targeted at specific inflammatory pathways now demonstrate efficacy for the prevention of major adverse cardiovascular events.

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Funding

Dr. Ajala is supported by National Heart, Lung, and Blood Institute of the National Institutes of Health (T32 HL007575). Dr. Everett is supported by NHLBI award R56 HL134810.

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  1. Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Ave, Boston, MA, 02215, USA

    Oluremi N. Ajala & Brendan M. Everett

  2. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Brendan M. Everett

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  1. Oluremi N. Ajala
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Correspondence to Brendan M. Everett.

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Brendan M. Everett reports personal consultancy fees from Amarin, Amgen, Gilead, FDA, Merck & Co., Novartis, NIDDK, and Roche Diagnostics outside the present work. Oluremi N. Ajala declare no conflict of interest relevant to this manuscript.

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Ajala, O.N., Everett, B.M. Targeting Inflammation to Reduce Residual Cardiovascular Risk. Curr Atheroscler Rep 22, 66 (2020). https://doi.org/10.1007/s11883-020-00883-3

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