High-dose NSAID + PPI + colchicine? It’s probably pericarditis

Inflammation of the pericardium, the double-layered sac that protects the heart and lubricates its movement, is termed pericarditis.1-3 This inflammation can sometimes also involve the myocardium, which is referred to as myopericarditis.Epidemiology and etiologyAs pericarditis can be self-limiting and occur in younger persons with no previous cardiac history, its occurrence is likely underreported. One study estimated the incidence to be 28 cases per 100,000 person-years.4 Pericarditis is often not severe enough to require admission to hospital, with a hospitalization rate of about three cases per 100,000 person-years.5 However, many patients present to the emergency department mistaking the chest pain for a myocardial infarction. The incidence is higher in men, with the highest risk group being men aged 16–65 years.2About 80%–90% of cases of pericarditis in developed countries are idiopathic (i.e., no identifiable cause), but are presumed to be due to a viral infection.1 In developing countries, tuberculosis is the most common cause.3 With respect to drug-induced causes, immune checkpoint inhibitors (e.g., pembrolizumab) have been associated with pericarditis.6 Acute pericarditis usually lasts one to two weeks with treatment, and there is no related long-term cardiac injury in most cases.1DiagnosisThe most characteristic symptom of pericarditis is sudden onset, sharp, pleuritic chest pain (i.e., worse with breathing), which can radiate to the back.2 It is often more intense when lying down and better when sitting upright. The diagnosis of pericarditis is based on the presence of two or more of the following four criteria: 1) characteristic chest pain; 2) pericardial effusion on an echocardiogram; 3) pericardial friction rub on cardiac auscultation; or 4) diffuse ST-segment elevation on an electrocardiogram.2 Inflammatory biomarkers (e.g., C-reactive protein, erythrocyte sedimentation rate) are often elevated as well.3TreatmentThe vast majority of acute pericarditis cases tend to respond quickly to initial treatment. First-line therapy is a high-dose nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen 600–800 mg every six to eight hours.2 High-dose acetylsalicylic acid (650–1000 mg every 8 hours) is also an option, but is typically preferred in patients with coronary artery disease. The initial duration of treatment is about one to two weeks until symptoms resolve for ≥ 24 hours, then the dosage is usually reduced (e.g., by 200–400 mg per dose of ibuprofen) every one to two weeks depending on the patient’s response (usually up to 4–6 weeks in total).2 A proton pump inhibitor (PPI) is frequently recommended as gastroprotection while patients are taking a high-dose NSAID, particularly in older patients or those with a history of peptic ulcer disease.Corticosteroids at low-to-moderate doses (e.g., prednisone 0.2–0.5 mg/kg daily) are second-line therapy due to a higher rate of recurrence. They are reserved for those who cannot take NSAIDs due to a contraindication, patients with autoimmune or inflammatory diseases, specific conditions (e.g., pregnancy, chronic kidney disease), or patients on oral anticoagulant therapy.7Colchicine is recommended as an adjunctive treatment in all initial and recurrent cases of pericarditis to improve symptom resolution and prevent recurrence. For initial cases, the dose is 0.6 mg once daily if the patient weighs ≤ 70 kg, or 0.6 mg twice daily if the patient is > 70 kg, for a duration of three months. This is primarily based on the ICAP trial, which demonstrated that colchicine decreased the rate of recurrence and persistent symptoms among 240 patients with acute pericarditis for a number needed to treat of five.8 Of note, the trials with colchicine in pericarditis used 0.5 mg immediate-release tablets, but only 0.6 mg immediate-release tablets are available in Canada.Normal activity can be resumed for most patients once they are asymptomatic and their inflammatory biomarkers normalize.2 Athletes should avoid strenuous activity or competitive sports for three months (until their diagnostic tests normalize), or six months for myopericarditis.Recurrent pericarditisUp to 30% of patients with pericarditis will have a recurrent episode after a symptom-free period of four to six weeks or longer.1-3 For recurrent pericarditis, first-line therapy is a retrial of a high-dose NSAID (with PPI) and colchicine.2 The NSAID dose and duration are similar to acute pericarditis. The dosing for colchicine is the same as for initial treatment, but the recommended duration is at least six months. This is based on the CORP and CORP-2 trials, in which colchicine reduced the recurrence of pericarditis at 18 months (number needed to treat of 4–5) among 360 patients with recurrent pericarditis.9,10 Low-to-moderate dose corticosteroids may be recommended in patients who have an incomplete response to NSAIDs and colchicine.2 Other drugs, such as anakinra, azathioprine or mycophenolate mofetil may be used in refractory cases.7Role of the pharmacistAs pericarditis can be quite distressing, especially among younger persons with no past medical history, it is important to reassure patients that it responds quickly to initial treatment and there is generally no long-term cardiac damage. However, due to the high recurrence rate, patients should be educated to monitor for recurrent symptoms. There is flexibility in the dose of ibuprofen and the tapering regimen should be based on the patient’s response. Some patients may require assistance with preparing a written tapering regimen. Finally, it is key to recommend that the PPI be discontinued at the same time as the high-dose NSAID so that the patient does not continue on it indefinitely.Arden Barry is a clinical pharmacy and research specialist in ambulatory cardiology at the Jim Pattison Outpatient Care and Surgery Centre in Surrey, BC, and associate professor (partner) at the Faculty of Pharmaceutical Sciences, University of British Columbia in Vancouver, BC.References:LeWinter MM. Acute pericarditis. N Engl J Med 2014;371:2410-6.Adler Y, Charron P, Imazio M, et al. 2015 ESC guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). Eur Heart J 2015;36:2921-64.Chiabrando JG, Bonaventura A, Vecchié A, et al. Management of acute and recurrent pericarditis: JACC state-of-the-art review. J Am Coll Cardiol 2020;75:76-92.Imazio M, Cecchi E, Demichelis B, et al. Myopericarditis versus viral or idiopathic acute pericarditis. Heart 2008;94:498-501.Kytö V, Sipilä J, Rautava P. Clinical profile and influences on outcomes in patients hospitalized for acute pericarditis. Circulation 2014;130:1601-6.Dolladille C, Akroun J, Morice PM, et al. Cardiovascular immunotoxicities associated with immune checkpoint inhibitors: a safety meta-analysis. Eur Heart J 2021;42:4964-77.Imazio M, Mardigyan V, Andreis A, et al. New developments in the management of recurrent pericarditis. Can J Cardiol 2023;39:1103-10.Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369:1522-8.Imazio M, Brucato A, Cemin R, et al. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann Intern Med 2011;155:409-14.Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet 2014;383:2232-7.

High-dose NSAID + PPI + colchicine? It’s probably pericarditis

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