The Efficacy and Safety of Colchicine for Pericarditis

Lutschinger LL, Rigopoulos AG, Schlattmann P, Matiakas M, Sedding D, Schulze PC, et al. Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome. BMC Cardiovasc Disord. 2019;19:207.

Study Population: 1981 patients with pericarditis from 10 trials

Reduction in pericarditis recurrence, rehospitalization rate, and symptom persistence after 72 hours

Adverse events including gastrointestinal intolerance, hepatotoxicity, pancreatitis, allergic reaction, renal failure, drug-withdrawal, alopecia, leucopenia, non-adherence, drug-withdrawal

Pericarditis accounts for up to 5% of patients presenting to the emergency department with chest pain and has an incidence of 28 cases per 100,000 person-years.1^, 2 Patients with pericarditis may present with chest pain, pericardial friction rub, electrocardiographic abnormalities, or pericardial effusion, and complications can be severe. Symptoms may recur after the initial episode in up to 50% of patients.2^, 3^, 4 While non-steroidal anti-inflammatory drugs are a major component of therapy for pericarditis, colchicine has been increasingly utilized and was recommended as first-line therapy by the 2015 European Society for Cardiology guidelines.5^, 6

The systematic review summarized here included randomized controlled trials (RCTs) evaluating > 10 patients treated with colchicine versus placebo in treatment and prevention of pericarditis.7 Secondary outcomes included rehospitalization rate, symptom duration beyond 72 hours, and adverse events.

The authors identified 10 RCTs (n=1981 patients) meeting inclusion criteria from an initial 361 studies. Of the 5 trials enrolling non-surgical pericarditis, 3 were double-blind and multicenter, while 2 were open-label (1 multicenter and 1 single center). Two included patients with first time acute pericarditis, and 3 included patients with recurrent pericarditis. Ultimately just one trial of first time acute pericarditis used double-blind methods and compared colchicine to placebo.

Colchicine was associated with an absolute reduction in recurrence by 20.1%, corresponding to a number-needed-to-treat (NNT) of 5 and a relative risk of (RR) of 0.5. It reduced rehospitalization by 4.7%, corresponding to a NNT of 22 and a RR of 0.7, and symptoms beyond 72 hours by 24.1%, corresponding to a NNT of 5 and a RR of 0.6. Colchicine was associated with an increased absolute risk of 3.5% for adverse events (number-needed-to-harm [NNH]=28), with gastrointestinal (GI) intolerance the most common adverse event.

This meta-analysis found that colchicine reduces the risk of recurrence, rehospitalization, and persistent symptoms among patients with pericarditis. There are important limitations to the applicability of these findings. While colchicine was initiated after clinical diagnosis and maintained for 3-6 months, dosing differed between studies, ranging from 0.5-1.5 mg. The follow up time also differed, ranging from 1 to 24 months. Only 2 trials evaluated patients with a first episode of acute pericarditis (others evaluated recurrent or post-surgical pericarditis), and just one of these used rigorous, double-blind methods. Moreover, all five trials of non-surgical patients were performed by a single research group in Italy. How this will translate to other settings is unclear. It is encouraging, if difficult to interpret, that the effects of colchicine on pericarditis symptoms and recurrence were similar across all 10 trials. For reliability and external validity, it will be important to see research groups in other settings reproduce these results. Based on funnel plot analysis, publication bias may have been present.

Significant heterogeneity was present in the populations studied, as well as the use of concomitant medications, such as NSAIDs. In this present meta-analysis, rates of patient withdrawal due to drug adverse effect occurred in 6.7-20% of included patients, though 4 of the 10 studies did not report the rate of patient withdrawal due to adverse effect. The most common adverse effect includes GI side effects such as nausea, vomiting, and diarrhea.8 Other side effects include fatigue, myalgias, paresthesias, hepatoxicity, bone marrow toxicity, and gout, which occur in less than 5% of patients. One meta-analysis suggests colchicine does not increase serious adverse events such as death and myotoxicity.8 Preexisting chronic renal disease increases the risk of side effects from colchicine. Importantly, colchicine has numerous contraindications including hepatic or renal dysfunction, elevated serum creatine kinase, anemia, leukopenia, thrombocytopenia, pregnancy, and allergy, which may limit its use in certain patients. Studies evaluated in this meta-analysis excluded patients with these contraindications.

Based on this evidence, we have assigned a color recommendation of Green (Benefit > Harm) in favor of colchicine for pericarditis. Further data are required evaluating colchicine for pericarditis in the ED setting, as well as further evaluation of contraindications and combination therapy.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

May 1, 2020