Expanding the evidence for effective therapies in recurrent pericarditis

Abstract

Recurrent pericarditis can be a clinical challenge for the physician and a frustrating experience for the patient. Most physicians will likely remember at least one patient who kept getting readmitted to the hospital every few months with recurrent pericardial effusion and symptoms of pericarditis, despite aggressive therapy with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine or steroids. While some patients do not even respond to second line therapy with steroids, others become steroid dependent and develop serious side effects from long-term treatment with this drug class. In addition to unsatisfactory symptom control and side effects, ineffective therapy of pericarditis may also lead to constrictive pericarditis – a severe long-term complication. Constrictive pericarditis is the result of heavy fibrosis of the pericardium, making it thickened and stiff, finally leading to right heart failure. Ultimately, this condition may require pericardiectomy – a procedure that is technically challenging with considerably high operative risk. In that regard, Bertog and colleagues have reported the outcomes of patients undergoing pericardiectomy for constrictive pericarditis (n1⁄4 163) over a 24-year period. The median follow-up among survivors was 6.9 years (range 0.8–24.5 years), during which 61 deaths (37%) occurred. Perioperative mortality was reported as 6% overall and was found to vary based on etiology. Patients with idiopathic constrictive pericarditis had the best prognosis, with a 7-year survival of 88% (95% confidence interval 76–94%), followed by post-surgical pericarditis reported as 66% (95% confidence interval 52–78%). Sagrista-Sauleda and colleagues have published a prospective study describing the clinical trajectory of pericarditis and its treatment. The group reported on a total of 1184 patients with pericarditis of whom 15 developed effusive-constrictive pericarditis. Seven (47%) of them required pericardiectomy. The major finding during the procedure was extensive thickening of the pericardium (visceral and parietal, up to 6mm each). The surgical procedure consisted of wide removal of both layers of the pericardium. The visceral layer required sharp dissection of many small fragments in order to obtain improved ventricular motion. Among the seven patients undergoing pericardiectomy, two patients (29%) died in the early postoperative period. Given the operative risk, it is of paramount importance that we, as physicians, exploit all conservative options of medical therapy available to prevent progression to a more advanced stage of the disease. The current treatment approach for pericarditis has been outlined in the 2015 European Society of Cardiology (ESC) guidelines for the diagnosis and management of pericardial disease by Adler and Charron from the ESC Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology. As illustrated in Figure 1, NSAIDS and colchicine are first-line therapy in pericarditis, while steroids can be used as second line therapy. As third line therapy, azathioprine and intravenous immunoglobulin (IVIG), as well as anakinra have been suggested based on data from small cohorts given the rather low prevalence of recurrent pericarditis. Anakinra, the drug investigated in the current article by Imazio and colleagues, has not been studied extensively. To date, there have only been case reports, small case series and one small randomized double blind, placebo controlled trial (n1⁄4 21) investigating its effects in recurrent pericarditis. Anakinra has been shown to reduce the risk of recurrent pericarditis over a median of 14 months, and to allow tapering of steroids in patients who had previously been steroid dependent. In order to evaluate the effects of anakinra in recurrent pericarditis in a broader patient population, Imazio and colleagues took the important step of