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.).

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).

Acute endocarditis of the patch caused by Staphylococcus capitis in treated tetralogy of Fallot. An unusual location by an unusual bacterium.

We present the case of a 46 year-old male, HCV infected, treated with corrective surgery for tetralogy of Fallot (TOF) immediately after percutaneous closure of the Blalock Taussig shunt. Four months later, the patient had infective endocarditis by Staphylococcus capitis localised on the right side of the patch, treated by oxacillin and gentamycin. The particularity of our report is the unusual location of the acute endocarditis and the bacterium involved: the pulmonary valve is much more likely to be involved in endocarditis in TOF patients and the patch endocarditis has rarely been reported. Moreover, Staphylococcus capitis has never been reported as a cause of acute endocarditis in corrected TOF patients. We believe that antibiotic therapy should be instituted as soon as possible even though an aggressive surgical treatment is mandatory to achieve complete recovery, mainly when clinical condition and inflammation markers do not improve.

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 degrees 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 degrees 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.

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.

Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial.

BACKGROUND: Colchicine seems to be a good drug for treating recurrences of pericarditis after conventional treatment failure, but no clinical trial has tested the effects of colchicine as first-line drug for the treatment of the first recurrence of pericarditis. METHODS: A prospective, randomized, open-label design was used to investigate the safety and efficacy of colchicine therapy as adjunct to conventional therapy for the first episode of recurrent pericarditis. Eighty-four consecutive patients with a first episode of recurrent pericarditis were randomly assigned to receive conventional treatment with aspirin alone or conventional treatment plus colchicine (1.0-2.0 mg the first day and then 0.5-1.0 mg/d for 6 months). When aspirin was contraindicated, prednisone (1.0-1.5 mg/kg daily) was given for 1 month and then was gradually tapered. The primary end point was the recurrence rate. Intention-to-treat analyses were performed by treatment group. RESULTS: During 1682 patient-months (mean follow-up, 20 months), treatment with colchicine significantly decreased the recurrence rate (actuarial rates at 18 months were 24.0% vs 50.6%; P = .02; number needed to treat = 4.0; 95% confidence interval 2.5-7.1) and symptom persistence at 72 hours (10% vs 31%; P = .03). In multivariate analysis, previous corticosteroid use was an independent risk factor for further recurrences (odds ratio, 2.89; 95% confidence interval, 1.10-8.26; P = .04). No serious adverse effects were observed. CONCLUSION: Colchicine therapy led to a clinically important and statistically significant benefit over conventional treatment, decreasing the recurrence rate in patients with a first episode of recurrent pericarditis.

Day-hospital treatment of acute pericarditis: a management program for outpatient therapy.

OBJECTIVES: We sought to investigate the safety and efficacy of a protocol for acute pericarditis triage and outpatient management of low-risk cases. BACKGROUND: Acute pericarditis has generally a brief and benign course after empiric treatment by non-steroidal anti-inflammatory drugs, and routine hospitalization of most patients may be unnecessary. METHODS: From January 1996 to December 2001, all consecutive cases of acute pericarditis were evaluated on a day-hospital basis. Patients without clinical poor prognostic predictors (fever >38 degrees C, subacute onset, immunodepression, trauma, oral anticoagulant therapy, myopericarditis, severe pericardial effusion, cardiac tamponade) were considered low-risk cases and assigned to outpatient treatment with high-dose oral aspirin. Patients with poor prognostic predictors or aspirin failure were hospitalized for etiology search and treatment. A clinical and echocardiographic follow-up was performed at 48 to 72 h, 7 to 10 days, 1 month, 6 months, and 1 year. RESULTS: Two hundred fifty-four out of 300 (84.7%) patients were selected as low-risk cases. Outpatient treatment was efficacious in 221 out of 254 (87%) cases. Thirty-three out of 254 patients were hospitalized because of aspirin failure. Patients treated on an out-of-hospital basis had no serious complications after a mean follow-up of 38 months (no cases of cardiac tamponade). A higher frequency of recurrences and constriction was recorded in aspirin-resistant cases than in aspirin responders (60.6% vs. 10.4% for recurrences and 9.1% vs. 0.5% for constriction, respectively; all p < 0.01). CONCLUSIONS: A protocol for acute pericarditis triage and outpatient therapy of low-risk cases is safe and efficacious and may reduce management costs.

Management, risk factors, and outcomes in recurrent pericarditis.

Fifty-five of 294 consecutive patients with acute pericarditis had first attacks of recurrent pericarditis and were evaluated and treated according to a management protocol. Corticosteroids were restricted to aspirin contraindication or failure. Colchicine was added in cases of aspirin and prednisone failure and was the treatment of choice for the second and subsequent recurrences. After logistic regression multivariate analysis, only the previous use of corticosteroids (odds ratio 10.35, 95% confidence interval 4.46 to 23.99, p <0.001) was associated with an increased risk for recurrence. After a mean follow-up of 72 months (range 48 to 108), a similar rate of complications was found in patients with or without recurrences.

Relation of acute pericardial disease to malignancy.

Neoplastic etiology was found in 33 of 450 patients with acute pericardial disease (7.3%). Acute pericardial disease was the first manifestation of previously unknown malignancies in 18 of 450 patients (4.0%), and lung cancer was the most common malignancy (72.2%, p = 0.02). The following clinical characteristics were associated with a greater probability of a neoplastic etiology: a history of malignancy (odds ratio [OR] 19.8), cardiac tamponade at presentation (OR 7.0), a lack of response to nonsteroidal anti-inflammatory drugs, and recurrent or incessant pericarditis (OR 10.0). A similar prognosis was found in patients with or without a history of known cancer.

Cardiovascular disease in HIV patients: from bench to bedside and backwards.

HIV patients are exposed to a higher risk of adverse cardiovascular events, due to complex interactions between traditional risk factors and HIV infection itself in terms of ongoing endothelial dysfunctional immune activation/inflammation and increased risk of thrombosis. On the other hand, long-span antiretroviral therapy administration still raises questions on its long-term safety in an era in which life expectancy is becoming longer and longer while treatment of non-HIV-related serious events is increasingly raising concern. In this article, we will critically analyse the current knowledge of pathological and clinical aspects pertaining to the increased risk of cardiovascular events associated with HIV.

Recurrent pain without objective evidence of disease in patients with previous idiopathic or viral acute pericarditis.

Recurrent pain without clinical evidence of acute pericarditis was recorded in 27 of 275 patients (9.8%; mean age 55.6 +/- 16.0 years, female/male ratio 20/7) with previous viral or idiopathic acute pericarditis. Female gender (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.8 to 10.6), previous use of corticosteroids (OR 5.2, 95% CI 2.2 to 12.3), and previous recurrent pericarditis (OR 3.7, 95% CI 1.3 to 10.2) were identified as risk factors for this syndrome. After a mean follow-up of 40 months, a higher recurrence rate was recorded in these patients (33.3% vs 14.1%; p = 0.02) as well as a nonsignificant trend to a higher rate of constrictive pericarditis.

Cardiovascular-associated disease in an addicted population: an observation study.

BACKGROUND: Illicit drugs such as cocaine, and methadone can induce acquired long QT syndrome. OBJECTIVE: The aim of this study was to evaluate the prevalence of cardiovascular disease and to assess the risk of torsades de pointes in substance abuse patients either with methadone or buprenorphine maintenance therapy, or without any specific therapy for opiate addiction. METHODS: From November 2008 to December 2009, 190 patients (153 men, mean age 38.2 years, 22-56 years) with a substance use disorder according to DSM IV TR criteria were included in the study. All patients underwent blood tests, serial electrocardiogram (ECG) and, when necessary, additional testing, including echocardiogram, exercise test and Holter monitoring. Age and sex-matched healthy controls were also evaluated and compared with the cases. RESULTS: One hundred and twenty-five patients (65.7%) had associated diseases. The prevalence of coronary artery disease and hypertension was, respectively, 2.1 and 5.2% in the addicted population. The percentage of abnormal ECGs was 34.2% in the addicted population and 4.7% in the nonaddicted population (P < 0.001). Twenty-five addicted patients had a QT interval prolongation (10 patients ≥ 480 ms). There were no sudden deaths or major cardiac events during the observation period. CONCLUSIONS: Our results indicate that the QT interval prolongation is not a negative prognostic marker in the addicted population, even with associated diseases. ECG should be performed when other drugs potentially prolonging QT interval are associated. Substance abuse patients should be followed by multidisciplinary teams, and blood tests and ECGs should be performed regularly.

Rationale and design of the COPPS trial: a randomised, placebo-controlled, multicentre study on the use of colchicine for the primary prevention of postpericardiotomy syndrome.

RATIONALE: Colchicine seems to be well tolerated and effective in the treatment and prevention of pericarditis. A preliminary clinical trial has shown that colchicine may be considered not only for the treatment of postpericardiotomy syndrome (PPS), but also for its primary prevention. STUDY DESIGN: The COPPS study is a multicentre, double-blind, randomised trial. On the third postoperative day, 360 patients, 180 in each treatment arm, will be randomised 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 > or =70 kg, and halved doses for patients <70 kg or intolerant to the highest dose). The primary efficacy endpoint is the incidence of PPS at 12 months. Secondary endpoints are disease-related hospitalisation, cardiac tamponade, constrictive pericarditis, and relapses at 18 months. Additional analysis will include the time to PPS. IMPLICATIONS: The COPPS trial will evaluate the use of colchicine for the primary prevention of PPS. This study will also provide important information on the frequency, clinical presentation, and prognosis of this syndrome in clinical practice.