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Here, we summarize preclinical and clinical findings supporting the key pathogenetic role of the NLRP3 inflammasome and IL-1 cytokines in the formation, progression, and complications of atherosclerosis, in ischemic (acute myocardial infarction), and nonischemic injury to the myocardium (myocarditis) and the progression to heart failure. We also review the clinically available IL-1 inhibitors, although not currently approved for cardiovascular indications, and discuss other IL-1 inhibitors, not currently approved, as well as oral NLRP3 inflammasome inhibitors currently in clinical development. Canakinumab, IL-1\u03b2 antibody, prevented the recurrence of ischemic events in patients with prior acute myocardial infarction in a large phase III clinical trial, including 10\u2009061 patients world-wide. Phase II clinical trials show promising data with anakinra, recombinant IL-1 receptor antagonist, in patients with ST-segment\u2013elevation acute myocardial infarction or heart failure with reduced ejection fraction. Anakinra also improved outcomes in patients with pericarditis, and it is now considered standard of care as second-line treatment for patients with recurrent\/refractory pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing IL-1\u03b1 and IL-1\u03b2, has also shown promising results in a phase II study in recurrent\/refractory pericarditis. In conclusion, there is overwhelming evidence linking the NLRP3 inflammasome and the IL-1 cytokines with the pathogenesis of cardiovascular diseases. The future will likely include targeted inhibitors to block the IL-1 isoforms, and possibly oral NLRP3 inflammasome inhibitors, across a wide spectrum of cardiovascular diseases.<\/jats:p>","DOI":"10.1161\/circresaha.120.315937","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T14:00:25Z","timestamp":1587650425000},"page":"1260-1280","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":734,"title":["Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease"],"prefix":"10.1161","volume":"126","author":[{"given":"Antonio","family":"Abbate","sequence":"first","affiliation":[{"name":"From the VCU Pauley Heart Center, Virginia Commonwealth University, Richmond (A.A., S.T., J.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Toldo","sequence":"additional","affiliation":[{"name":"From the VCU Pauley Heart Center, Virginia Commonwealth 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