Table 3.

Anti-inflammatory therapeutics

Agent	Specific targets	Beneficial effects	Limitations or adverse effects	Refs.
COX inhibitors	COX1 and COX2	Suppress the production of arachidonic acid metabolites (prostaglandins, leukotrienes, thromboxane A2) Reduce NLRP3 activity, inhibit caspase 1 and prevent IL-1β secretion Reduce pain	Increase risk of clots, hypertension and cardiovascular events	173,177
Aspirin	COX1 and COX2	Irreversible acetylation of COXs Acetylated COX2 can metabolize docosahexaenoic acid and eicosapentaenoic acid Production of aspirin-triggered resolvins Restrains NLRP3 assembly and activity via blockade of reactive oxygen species release	No evidence of atrial fibrillation prevention with chronic aspirin use Not recommended for patients with low risk of cardiovascular disease	184,273
Glucocorticoids	Immune cells and pro-inflammatory biomarkers	Suppress pro-inflammatory biomarkers and activation of pro-inflammatory cells Promote clearance of apoptotic cells Reduce pain and swelling	Increase NLRP3 activation and IL-1β secretion Delay wound healing Increase the risk of hypertension Increase atrial fibrillation incidence	185
NLRP3 inhibitors	NLRP3 inflammasome components and signalling	Prevent maturation of NLRP3 components Prevent NLRP3 inflammasome assembly Reduce pro-inflammatory cytokine production Might promote lipid-mediator class switching	Further studies are required to assess the potential of NLRP3 inhibitors in inflammatory conditions and clarify their safety and potential adverse effects	195
IL-1 inhibitors	IL-1R1 and IL-1β	Prevent IL-1β interaction with its receptor IL-1R1 Inhibit IL-1β signalling Reduce IL-1β-induced production of pro-inflammatory interleukins (IL-6, IL-17, IL-18)	Increase the risk of infection Increase cholesterol plasma levels Decrease circulating leukocyte numbers Might increase the risk of cancer	102
Specialized pro-resolving mediators	Pro-inflammatory processes and immune cells	Prevent infiltration of polymorphonuclear leukocytes Activate M2 macrophage phagocytosis and clearance of cellular debris Resolvin D1 decreases atrial expression of NLRP3 components Non-toxic	Few clinical and preclinical data on cardiac tissue currently available Various clinical trials are ongoing or have been completed: NCT04575753, NCT04997057, NCT03609541, NCT04697719, NCT02322073	274–278

COX, cyclooxygenase; IL-1R1, IL-1 receptor type 1; NLRP3, NACHT-, LRR- and pyrin domain-containing 3.