The intracellular sensing protein termed NLRP3 (for NACHT, LRR, and PYD 
domains-containing protein 3) forms a macromolecular structure called the NLRP3 
inflammasome. The NLRP3 inflammasome plays a major role in inflammation, 
particularly in the production of IL (interleukin)-1β. IL-1β is the most studied 
of the IL-1 family of cytokines, including 11 members, among which are IL-1α and 
IL-18. 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-1β 
antibody, prevented the recurrence of ischemic events in patients with prior 
acute myocardial infarction in a large phase III clinical trial, including 
10 061 patients world-wide. Phase II clinical trials show promising data with 
anakinra, recombinant IL-1 receptor antagonist, in patients with 
ST-segment-elevation 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-1α and IL-1β, 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.