Rita Trinchero

Colchicine in Addition to Conventional Therapy for Acute Pericarditis Results of the COlchicine for acute PEricarditis (COPE) Trial

Background—Colchicine is effective and safe for the treatment and prevention of recurrent pericarditis and might ultimately serve as the initial mode of treatment, especially in idiopathic cases. The aim of this work was to verify the safety and efficacy of colchicine as an adjunct to conventional therapy for the treatment of the first episode of acute pericarditis. Methods and Results—A prospective, randomized, open-label design was used. A total of 120 patients (mean age 56.9±18.8 years, 54 males) with a first episode of acute pericarditis (idiopathic, viral, postpericardiotomy syndromes, and connective tissue diseases) were randomly assigned to conventional treatment with aspirin (group I) or conventional treatment plus colchicine 1.0 to 2.0 mg for the first day and then 0.5 to 1.0 mg/d for 3 months (group II). Corticosteroid therapy was restricted to patients with aspirin contraindications or intolerance. The primary end point was recurrence rate. During the 2873 patient-month follow-up, colchicine significantly reduced the recurrence rate (recurrence rates at 18 months were, respectively, 10.7% versus 32.3%; P=0.004; number needed to treat=5) and symptom persistence at 72 hours (respectively, 11.7% versus 36.7%; P=0.003). After multivariate analysis, corticosteroid use (OR 4.30, 95% CI 1.21 to 15.25; P=0.024) was an independent risk factor for recurrences. Colchicine was discontinued in 5 cases (8.3%) because of diarrhea. No serious adverse effects were observed. Conclusions—Colchicine plus conventional therapy led to a clinically important and statistically significant benefit over conventional treatment, decreasing the recurrence rate in patients with a first episode of acute pericarditis. Corticosteroid therapy given in the index attack can favor the occurrence of recurrences.

Indicators of Poor Prognosis of Acute Pericarditis

Background— The clinical search for indicators of poor prognosis of acute pericarditis may be useful for clinical triage of patients at high risk of specific causal conditions or complications. The aim of the present article is to assess the relationship between clinical features at presentation and specific causes or complications. Methods and Results— A total of 453 patients aged 17 to 90 years (mean age 52±18 years, 245 men) with acute pericarditis (post–myocardial infarction pericarditis was excluded) were prospectively evaluated from January 1996 to August 2004. A specific cause was found in 76 of 453 patients (16.8%): autoimmune in 33 patients (7.3%), neoplastic in 23 patients (5.1%), tuberculous in 17 patients (3.8%), and purulent in 3 patients (0.7%). In multivariable analysis, women (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; P=0.036) and patients with fever >38°C (HR 3.56, 95% CI 1.82 to 6.95; P<0.001), subacute course (HR 3.97, 95% CI 1.66 to 9.50; P=0.002), large effusion or tamponade (HR 2.15, 95% CI 1.09 to 4.23; P=0.026), and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 2.50, 95% CI 1.28 to 4.91; P=0.008) were at increased risk of specific causal conditions. After a mean follow-up of 31 months, complications were detected in 95 patients (21.0%): recurrences in 83 patients (18.3%), tamponade in 14 patients (3.1%), and constriction in 7 patients (1.5%). In multivariable analysis, women (HR 1.65, 95% CI 1.08 to 2.52; P=0.020) and patients with large effusion or tamponade (HR 2.51, 95% CI 1.37 to 4.61; P=0.003) and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 5.50, 95% CI 3.56 to 8.51; P<0.001) were at increased risk of complications. Conclusions— Specific clinical features (fever >38°C, subacute course, large effusion or tamponade, and aspirin or NSAID failure) may be useful to identify higher risk of specific causal conditions and complications.

Controversial Issues in the Management of Pericardial Diseases

The management of pericardial diseases is largely empirical because of the relative lack of randomized trials. The first published guidelines1,2 are a first attempt to organize current knowledge. At present, no specific guidelines have been issued by the American Heart Association and American College of Cardiology. After a literature review including a Medline search with the MeSH terms “pericarditis” and “pericardium,” we identified the following controversial issues related mainly to the management of pericarditis and pericardial effusion: (1) etiological search and hospitalization; (2) role of pericardiocentesis, pericardial biopsy, and pericardioscopy; (3) myopericarditis; (4) use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and colchicine; (5) management of refractory cases and long-term outcome; (6) role of pericardiectomy, pericardial window, and other interventional techniques; and (7) management of chronic idiopathic pericardial effusion. At the end of each issue, key points are summarized. Management of most cases is done by general practitioners or different healthcare specialists and does not require specific expertise; nevertheless, incessant and recurrent cases and specific forms (eg, tuberculous pericarditis, neoplastic pericardial disease, autoimmune conditions) require cooperation among specialties (eg, cardiology, infectious diseases, rheumatology, oncology). Specific interventional techniques (eg, pericardioscopy) and pericardiectomy should be performed in referral centers. ### Pericarditis Although the clinical diagnosis of pericarditis is relatively simple (Tables 1 and 2⇓),1–13 establishing the cause may be more difficult. A major controversy in “pericardiology” is the role of an extensive etiologic search and hospital admission for all patients with pericarditis or pericardial effusion.1–8 The causes of pericarditis are varied (Table 3),9 and the clinician should identify causes that require targeted therapies. The epidemiological background is essential to develop a rational cost-effective management program3,4,15,16; the approach may be different for research, when we attempt to reduce the number of “idiopathic” cases. In developed countries, idiopathic …

Colchicine for Recurrent Pericarditis (CORP): A Randomized Trial

BACKGROUND Recurrence is the most common complication of pericarditis, affecting 10% to 50% of patients. OBJECTIVE To evaluate the efficacy and safety of colchicine for the secondary prevention of recurrent pericarditis. DESIGN Prospective, randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov registration number: NCT00128414) SETTING: 4 general hospitals in urban areas of Italy. PATIENTS 120 patients with a first recurrence of pericarditis. INTERVENTION In addition to conventional treatment, patients were randomly assigned to receive either placebo or colchicine, 1.0 to 2.0 mg on the first day followed by a maintenance dose of 0.5 to 1.0 mg/d, for 6 months. MEASUREMENTS The primary study end point was the recurrence rate at 18 months. Secondary end points were symptom persistence at 72 hours, remission rate at 1 week, number of recurrences, time to first recurrence, disease-related hospitalization, cardiac tamponade, and rate of constrictive pericarditis. RESULTS At 18 months, the recurrence rate was 24% in the colchicine group and 55% in the placebo group (absolute risk reduction, 0.31 [95% CI, 0.13 to 0.46]; relative risk reduction, 0.56 [CI, 0.27 to 0.73]; number needed to treat, 3 [CI, 2 to 7]). Colchicine reduced the persistence of symptoms at 72 hours (absolute risk reduction, 0.30 [CI, 0.13 to 0.45]; relative risk reduction, 0.56 [CI, 0.27 to 0.74]) and mean number of recurrences, increased the remission rate at 1 week, and prolonged the time to subsequent recurrence. The study groups had similar rates of side effects and drug withdrawal. LIMITATION Multiple recurrences and neoplastic or bacterial causes were excluded. CONCLUSION Colchicine is safe and effective for secondary prevention of recurrent pericarditis.

A Randomized Trial of Colchicine for Acute Pericarditis

BACKGROUND Colchicine is effective for the treatment of recurrent pericarditis. However, conclusive data are lacking regarding the use of colchicine during a first attack of acute pericarditis and in the prevention of recurrent symptoms. METHODS In a multicenter, double-blind trial, eligible adults with acute pericarditis were randomly assigned to receive either colchicine (at a dose of 0.5 mg twice daily for 3 months for patients weighing >70 kg or 0.5 mg once daily for patients weighing ≤70 kg) or placebo in addition to conventional antiinflammatory therapy with aspirin or ibuprofen. The primary study outcome was incessant or recurrent pericarditis. RESULTS A total of 240 patients were enrolled, and 120 were randomly assigned to each of the two study groups. The primary outcome occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (relative risk reduction in the colchicine group, 0.56; 95% confidence interval, 0.30 to 0.72; number needed to treat, 4; P<0.001). Colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%, P=0.001), the number of recurrences per patient (0.21 vs. 0.52, P=0.001), and the hospitalization rate (5.0% vs. 14.2%, P=0.02). Colchicine also improved the remission rate at 1 week (85.0% vs. 58.3%, P<0.001). Overall adverse effects and rates of study-drug discontinuation were similar in the two study groups. No serious adverse events were observed. CONCLUSIONS In patients with acute pericarditis, colchicine, when added to conventional antiinflammatory therapy, significantly reduced the rate of incessant or recurrent pericarditis. (Funded by former Azienda Sanitaria Locale 3 of Turin [now Azienda Sanitaria Locale 2] and Acarpia; ICAP ClinicalTrials.gov number, NCT00128453.).

Colchicine Reduces Postoperative Atrial Fibrillation Results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) Atrial Fibrillation Substudy

Background— Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. Methods and Results— The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P =0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P =0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P =0.009). Side effects were similar in the study groups. Conclusion— Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay. Clinical Trial Registration— URL: . Unique identifier: [NCT00128427][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00128427&atom=%2Fcirculationaha%2F124%2F21%2F2290.atomBackground— Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. Methods and Results— The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P=0.009). Side effects were similar in the study groups. Conclusion— Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00128427.

COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial

AIMS No drug has been proven efficacious to prevent the post-pericardiotomy syndrome (PPS), but colchicine seems safe and effective for the treatment and prevention of pericarditis. The aim of the COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS) trial is to test the efficacy and safety of colchicine for the primary prevention of the PPS. METHODS AND RESULTS The COPPS study is a multicentre, double-blind, randomized trial. On the third post-operative day, 360 patients (mean age 65.7 ± 12.3 years, 66% males), 180 in each treatment arm, were randomized to receive placebo or colchicine (1.0 mg twice daily for the first day followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, and halved doses for patients <70 kg or intolerant to the highest dose). The primary efficacy endpoint was the incidence of PPS at 12 months. Secondary endpoint was the combined rate of disease-related hospitalization, cardiac tamponade, constrictive pericarditis, and relapses. Baseline characteristics were well balanced between the study groups. Colchicine significantly reduced the incidence of the PPS at 12 months compared with placebo (respectively, 8.9 vs. 21.1%; P = 0.002; number needed to treat = 8). Colchicine also reduced the secondary endpoint (respectively, 0.6 vs. 5.0%; P = 0.024). The rate of side effects (mainly related to gastrointestinal intolerance) was similar in the colchicine and placebo groups (respectively, 8.9 vs. 5.0%; P = 0.212). CONCLUSION Colchicine is safe and efficacious in the prevention of the PPS and its related complications and may halve the risk of developing the syndrome following cardiac surgery. ClinicalTrials.gov number, NCT00128427.

Corticosteroids for Recurrent Pericarditis High Versus Low Doses: A Nonrandomized Observation

Background— Corticosteroid use is widespread in recurrent pericarditis, even if rarely indicated, and high doses (eg, prednisone 1.0 to 1.5 mg · kg−1 · d−1) are generally recommended, although only weak evidence supports their use with possible severe side effects. The aim of this work was to compare side effects, recurrences and other complications, and hospitalizations of a low- versus high-dose regimen of prednisone for recurrent pericarditis. Methods and Results— A retrospective review of all cases of recurrent pericarditis treated with corticosteroids according to different regimens from January 1996 to June 2004 was performed in 2 Italian referral centers. One hundred patients with recurrent pericarditis (mean age, 50.1±15.8 years; 57 females) were included in the study; 49 patients (mean age, 47.5±16.0; 25 females) were treated with low doses of prednisone (0.2 to 0.5 mg · kg−1 · d−1), and 51 patients (mean age, 52.6±15.3; 32 females) were treated with prednisone 1.0 mg · kg−1 · d−1. Baseline demographic and clinical characteristics were well balanced across the groups. Each initial dose was maintained for 4 weeks and then slowly tapered. After adjustment for potential confounders (age, female gender, nonidiopathic origin), only high doses of prednisone were associated with severe side effects, recurrences, and hospitalizations (hazard ratio, 3.61; 95% confidence interval, 1.96 to 6.63; P<0.001). Conclusions— Use of higher doses of prednisone (1.0 mg · kg−1 · d−1) for recurrent pericarditis is associated with more side effects, recurrences, and hospitalizations. Lower doses of prednisone should be considered when corticosteroids are needed to treat pericarditis.

Myopericarditis versus viral or idiopathic acute pericarditis

Objective: To investigate the relative incidence, clinical presentation and prognosis of myopericarditis among patients with idiopathic or viral acute pericarditis. Design: Prospective observational clinical cohort study. Setting: Two general hospitals from an urban area of 220 000 inhabitants. Patients: 274 consecutive cases of idiopathic or viral acute pericarditis between January 2001 and June 2005. Main outcome measures: Relative prevalence of myopericarditis. Clinical features at presentation including echocardiographic data (ejection fraction (EF), wall motion score index (WMSI)) and follow-up data at 12 months including complications, results of echocardiography, electrocardiography and treadmill testing. Results: Myopericarditis was recorded in 40/274 (14.6%) consecutive patients. At presentation, the following clinical features were independently associated with myopericarditis: arrhythmias (odds ratio (OR) = 17.6, 95% confidence interval (CI) 5.7 to 54.1; p<0.001), male gender (OR = 6.4, 95% CI 2.3 to 18.4; p = 0.01), age <40 years (OR = 6.1, 95% CI 2.2 to 16.9; p = 0.01), ST elevation (OR = 5.4, 95% CI 1.4 to 20.5; p = 0.013) and a recent febrile syndrome (OR = 2.8, 95% CI 1.1 to 7.7; p = 0.044). After 12 months’ follow-up an increase of EF (basal EF 49.6 (5.1)% vs 12-month EF 59.1 (4.6)%; p<0.001) and decrease of WMSI (basal WMSI 1.19 (0.27) vs 12-month WMSI 1.02 (0.09); p<0.001) were recorded in patients with myopericarditis, with a normalisation of echocardiography, electrocardiography and treadmill testing in 98% of cases. Use of heparin or other anticoagulants (OR = 1.1, 95% CI 0.3 to 3.5; p = 0.918) and myopericarditis (OR = 2.3, 95% CI 0.7 to 7.6; p = 0.187) was not associated with an increased risk of cardiac tamponade or recurrences. Conclusions: Myopericarditis is relatively common and shows a benign evolution also in spontaneous cases not related to vaccination.

Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial

BACKGROUND Colchicine is effective for the treatment of acute pericarditis and first recurrences. However, conclusive data are lacking for the efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis. METHODS We did this multicentre, double-blind trial at four general hospitals in northern Italy. Adult patients with multiple recurrences of pericarditis (≥two) were randomly assigned (1:1) to placebo or colchicine (0·5 mg twice daily for 6 months for patients weighing more than 70 kg or 0·5 mg once daily for patients weighing 70 kg or less) in addition to conventional anti-inflammatory treatment with aspirin, ibuprofen, or indometacin. Permuted block randomisation (size four) was done with a central computer-based automated sequence. Patients and all investigators were masked to treatment allocation. The primary outcome was recurrent pericarditis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00235079. FINDINGS 240 patients were enrolled and 120 were assigned to each group. The proportion of patients who had recurrent pericarditis was 26 (21·6%) of 120 in the colchicine group and 51 (42·5%) of 120 in the placebo group (relative risk 0·49; 95% CI 0·24-0·65; p=0·0009; number needed to treat 5). Adverse effects and discontinuation of study drug occurred in much the same proportions in each group. The most common adverse events were gastrointestinal intolerance (nine patients in the colchicine group vs nine in the placebo group) and hepatotoxicity (three vs one). No serious adverse events were reported. INTERPRETATION Colchicine added to conventional anti-inflammatory treatment significantly reduced the rate of subsequent recurrences of pericarditis in patients with multiple recurrences. Taken together with results from other randomised controlled trials, these findings suggest that colchicine should be probably regarded as a first-line treatment for either acute or recurrent pericarditis in the absence of contraindications or specific indications. FUNDING Azienda Sanitaria 3 of Torino (now ASLTO2).