Current Drug Treatment for Acute and Recurrent Pericarditis

Abstract

Pericarditis is the most frequent pericardial disease and presents with a relatively benign course when treated according to guideline-directed therapies at first presentation. Recurrence is the most frequent complication and may occur more frequently after a first episode, in patients with autoimmune etiology, in patients who received glucocorticoids, or after rapid (i.e., within 1 month) tapering of anti-inflammatory drugs. The therapeutic armamentarium for pericarditis includes high-dose nonsteroidal anti-inflammatory drugs (NSAIDs) that are tapered rapidly once symptoms are controlled. Colchicine is necessary to both relieve symptoms and reduce the rate of recurrences and is continued for at least 3-6 months. Low- to moderate-dose glucocorticoids are reserved for patients with a first recurrence for which NSAIDs and colchicine failed and/or who have an autoimmune disorder, with a slow tapering. Interleukin-1 blockers-anakinra, rilonacept, and goflikicept-are used as a third-line option in patients who cannot come off glucocorticoids or as second-line therapy after NSAIDs and colchicine in patients with contraindications to glucocorticoids or in those with high-risk features (i.e., multiple episodes, markedly elevated inflammatory markers, or extensive abnormalities at pericardial imaging) in whom treatment with glucocorticoids is unlikely to succeed.

Fig. 1

Pathogenic mechanisms driving pericardial inflammation and mechanisms of action of anti-inflammatory drugs. Injury to the pericardium triggers the release of damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), leading to the activation of nuclear factor kappa light-chain enhancer of activated b (NF-kB) cells, which enhances the transcription of inflammatory precursors and associated cytokines (such as NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3], apoptosis-associated speck-like protein containing a caspase-recruiting domain [ASC], and pro-caspase-1 and pro-interleukin [IL]-1β) necessary for the formation of the NLRP3 inflammasome. This process ultimately results in the release of IL-1β. NF-kB also promotes the synthesis of phospholipase-A2, driving the arachidonic acid pathway and the production of prostaglandins (PG) and thromboxanes (TXA). The IL-1 receptor (IL-1R) plays a key role, as IL-1α acts as an alarmin or DAMP during tissue injury, and IL-1β is processed and released by the inflammasome, amplifying the inflammatory response. Also, IL-1R activation on endothelial cells plays a role in immune cell migration. CBD, cannabidiol; COX, cyclooxygenase; NSAID, nonsteroidal anti-inflammatory drug; PLA2, phospholipase A2; TLR, toll-like receptor.

Fig. 2

Flowchart for the management of recurrent pericarditis. When first-line therapies fail, interleukin (IL)-1 blockers should be considered in patients with recurrent pericarditis, either in case of resistance to colchicine and dependence on glucocorticoids or in the presence of high-risk features such as multiple episodes, markedly elevated inflammatory markers, or extensive abnormalities at pericardial imaging. CMR, cardiac magnetic resonance; CRP, C-reactive protein; IVIG, intravenous immunoglobulins; NRS, numerical rating scale; NSAIDs, nonsteroidal anti-inflammatory drugs. Modified with permission from Del Buono et al. [132].