Targeting Inflammation to Reduce Residual Cardiovascular Risk
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NONSTATIN DRUGS (M. VRABLIK, SECTION EDITOR)
Targeting Inflammation to Reduce Residual Cardiovascular Risk Oluremi N. Ajala 1 & Brendan M. Everett 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Inflammation . Residual risk . Prevention . Atherosclerosis . Cardiovascular disease
Introduction Atherosclerotic cardiovascular disease remains a major cause of death worldwide despite significant progress in preventing, diagnosing, and treating the disease and its complications [1]. Efforts to prevent a first major cardiovascular event (“primary prevention”) and recurrent events among those with established atherosclerotic cardiovascular disease (ASCVD) (“secondary prevention”) have led to substantial reductions in cardiovascular morbidity and mortality in many parts of
This article is part of the Topical Collection on Nonstatin Drugs * Brendan M. Everett [email protected] 1
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Ave, Boston, MA 02215, USA
2
Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
the world [2–4]. Despite this progress, however, patients with established cardiovascular disease remain at high risk for recurrent events, eve
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