Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a ‘real world’ population. This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9–33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3–12), pericarditis recurrences were reduced six-fold (2.33–0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08–0.10 per patient per year), hospitalisations were reduced seven-fold (0.99–0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence. In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.

The COVID-19 pandemic is challenging our cardiovascular care of patients with heart diseases. In the setting of pericardial diseases, there are two possible different scenarios to consider: the patient being treated for pericarditis who subsequently becomes infected with SARS-CoV-2, and the patient with COVID-19 who develops pericarditis or pericardial effusion. In both conditions, clinicians may be doubtful regarding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine, and biological agents, such as anti-IL1 agents (e.g. anakinra), that are the mainstay of therapy for pericarditis. For NSAIDs, there is no clear scientific evidence linking ibuprofen and other NSAIDs to worsening of COVID-19; however, it seems prudent to continue them, if necessary to control pericarditis, and on the other hand, to prefer paracetamol for fever and systemic symptoms related to COVID-19. Treatments with corticosteroids, colchicine, and anakinra appear well tolerated in the context of COVID-19 infection and are currently actively evaluated as potential therapeutic options for COVID infection at different stages of the disease. On this basis, currently most treatments for pericarditis do not appear contraindicated also in the presence of possible COVID-19 infection and should not be discontinued, and some (corticosteroids, colchicine, and anakinra) can be considered to treat both conditions.

Colchicine is an ancient drug, traditionally used for the treatment and prevention of gouty attacks; it has become standard of treatment for pericarditis with a potential role in the treatment of coronary artery disease. Atherosclerotic plaque formation, progression, destabilisation and rupture are influenced by active proinflammatory cytokines interleukin (IL)-1β and IL-18 that are generated in the active forms by inflammasomes, which are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Colchicine has a unique anti-inflammatory mechanism: it is not only able to concentrate in leucocytes, especially neutrophils, and block tubulin polymerisation, affecting the microtubules assembly, but also inhibits (NOD)-like receptor protein 3 (NLRP3) inflammasome. On this basis, colchicine interferes with several functions of leucocytes and the assembly and activation of the inflammasome as well, reducing the production of interleukin 1β and interleukin 18. Long-term use of colchicine has been associated with a reduced rate of cardiovascular events both in chronic and acute coronary syndromes, with an overall good safety profile. This review will focus on the influence of colchicine on the pathophysiology of coronary artery disease, reviewing essential pharmacology and discussing the most important and recent clinical studies. On the basis of current literature, colchicine is emerging as a possible new valuable, safe and cheap agent for the treatment of acute and chronic coronary syndromes.

Objective Frequent flares of pericardial inflammation in recurrent or incessant pericarditis with corticosteroid dependence and colchicine resistance may represent a risk factor for constrictive pericarditis (CP). This study was aimed at the identification of CP in these patients, evaluating the efficacy and safety of anakinra, a third-line treatment based on interleukin-1 inhibition, to treat CP and prevent the need for pericardiectomy. Methods Consecutive patients with recurrent or incessant pericarditis with corticosteroid dependence and colchicine resistance were included in a prospective cohort study from 2015 to 2018. Enrolled patients received anakinra 100 mg once daily subcutaneously. The primary end point was the occurrence of CP. A clinical and echocardiographic follow-up was performed at 1, 3, 6 months and then every 6 months. Results Thirty-nine patients (mean age 42 years, 67% females) were assessed, with a baseline recurrence rate of 2.76 flares/patient-year and a median disease duration of 12 months (IQR 9–20). During follow-up, CP was diagnosed in 8/39 (20%) patients. After anakinra dose of 100 mg/day, 5 patients (63%) had a complete resolution of pericardial constriction within a median of 1.2 months (IQR 1–4). In other three patients (37%), CP became chronic, requiring pericardiectomy within a median of 2.8 months (IQR 2–5). CP occurred in 11 patients (28%) with incessant course, which was associated with an increased risk of CP over time (HR for CP 30.6, 95% CI 3.69 to 253.09). Conclusions In patients with recurrent or incessant pericarditis, anakinra may have a role in CP reversal. The risk of CP is associated with incessant rather than recurrent course.

Aims Corticosteroid-dependent and colchicine-resistant recurrent pericarditis (RP) is a challenging management problem, in which conventional anti-inflammatory therapy (nonsteroidal anti-inflammatory drugs, colchicine, corticosteroids) is unable to control the disease. Recent data suggest a potential role for anti-interleukin-1 (IL-1) agents for this condition. This study was designed to assess the safety and efficacy of anti-IL-1 agents in this setting. Methods We performed a systematic review and meta-analysis of randomised controlled trials and observational studies assessing pericarditis recurrences and drug-related adverse events in patients receiving anti-IL-1 drugs for pericarditis. Results The meta-analysis assessed 7 studies including 397 pooled patients with RP. The median age was 42 years, 60% were women and the aetiology was idiopathic in 87%. After a median follow-up of 14 months (IQR,12–39), patients receiving anti-IL-1 agents (anakinra or rilonacept) had a significantly reduction in pericarditis recurrences (incidence rate ratio 0.06, 95% CI 0.03 to 0.14), compared with placebo and/or standard medical therapy. Anti-IL-1 agents were associated with increased risk of adverse events compared with placebo (risk ratio (RR) 5.38, 95% CI 2.08 to 13.92): injection-site reactions occurred in 15/41 (36.6%) vs none (RR 14.98, 95% CI 2.09 to 107.09), infections occurred in 13/51 (25.5%) vs 3/41 (7.3%; RR 3.65, 95% CI 1.23 to 10.85). Anti-IL-1 agents were not associated with increased risk of severe adverse events. Conclusions In patients with RP, anti-IL-1 agents (anakinra and rilonacept) are efficacious for prevention of recurrences, without severe adverse events.

Aims Contrast-induced acute kidney injury (CIAKI) in patients with chronic kidney disease undergoing coronary angiography or percutaneous coronary intervention is a common iatrogenic complication associated with increased morbidity and mortality. This study compares sodium bicarbonate/isotonic saline/N-acetylcysteine/vitamin C prophylaxis (BS-NAC) against high-volume forced diuresis with matched hydration in CIAKI prevention. Methods One-hundred and thirty-three consecutive patients undergoing coronary angiography or percutaneous coronary intervention with estimated glomerular filtration rate less than 60 mL/min/1.73m2 were randomized to the study group receiving matched hydration (MHG) or to the control group receiving BS-NAC. MHG received in vein (i.v.) 250 mL isotonic saline bolus, followed by a 0.5 mg/kg furosemide i.v. bolus to forced diuresis. A dedicated device automatically matched the isotonic saline i.v. infusion rate to the urinary output for 1 h before, during and 4 h after the procedure. Results MHG had the lowest incidence of CIAKI (7 vs. 25%, P = 0.01), major adverse cardiac and cerebrovascular events at 1 year (7 vs. 32%, P < 0.01) and readmissions to cardiology/nephrology departments (8 vs. 25%, P = 0.03; hospitalization days 1.0 ± 3.8 vs. 4.9 ± 12.5, P = 0.01). Three months after the procedure the decrease in the estimated glomerular filtration rate was 0.02% for MHG versus 15% for the control group. Conclusion Matched hydration was more effective than BS-NAC in CIAKI prevention. One-year follow-up showed that matched hydration was associated also with limited chronic kidney disease progression, major adverse cardiac and cerebrovascular events and hospitalizations.