Article

A Randomized Trial of Colchicine for Acute Pericarditis

the Internal Medicine Department, St. Vincent Hospital, Worcester, MA (D.H.S.)
New England Journal of Medicine (Impact Factor: 55.87). 08/2013; 369(16):130831233005005. DOI: 10.1056/NEJMoa1208536

ABSTRACT

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. ResultsA 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.)

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original article
A Randomized Trial of Colchicine
for Acute Pericarditis
Massimo Imazio, M.D., Antonio Brucato, M.D., Roberto Cemin, M.D.,
Stefania Ferrua, M.D., Stefano Maggiolini, M.D., Federico Beqaraj, M.D.,
Daniela Demarie, M.D., Davide Forno, M.D., Silvia Ferro, M.D.,
Silvia Maestroni, M.D., Riccardo Belli, M.D., Rita Trinchero, M.D.,
David H. Spodick, M.D., and Yehuda Adler, M.D., for the ICAP Investigators*
From the Cardiology Department, Maria
Vittoria Hospital, Turin (M.I., F.B., D.D.,
D.F., S.F., R.B., R.T.), the Internal Medi-
cine Department, Ospedale Papa
Giovanni XXIII, Bergamo (A.B., S. Mae-
stroni), the Cardiology Department, San
Maurizio Regional Hospital, Bolzano
(R.C.), the Cardiology Department, Os-
pedale degli Infermi, Rivoli (S.F.), and the
Cardiovascular Department, S. Leopoldo
Mandic Hospital, Merate (S. Maggiolini)
all in Italy; the Internal Medicine De-
partment, St. Vincent Hospital, Worces-
ter, MA (D.H.S.); and Chaim Sheba Medi-
cal Center, Tel Hashomer and Sacker
Faculty of Medicine, Tel Aviv, Israel
(Y.A.). Address reprint requests to Dr.
Imazio at the Cardiology Department,
Maria Vittoria Hospital, Via Luigi Cibrario
72, 10141 Turin, Italy, or at massimo_
imazio@yahoo.it.
*A full list of trial investigators and com-
mittees in the Investigation on Colchi-
cine for Acute Pericarditis (ICAP) study
is provided in the Supplementary Ap-
pendix, available at NEJM.org.
This article was published on September 1,
2013, at NEJM.org.
N Engl J Med 2013.
DOI: 10.1056/NEJMoa1208536
Copyright © 2013 Massachusetts Medical Society
Abstr act
Background
Colchicine is effective for the treatment of recurrent pericarditis. However, conclu-
sive 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 reduc-
tion 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). Colchi-
cine 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 anti-
inflammatory 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.)
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C
olchicine has been used for centu-
ries to treat and prevent gouty attacks
1
and more recently has been recommend-
ed to treat and prevent serositis in patients with
familial Mediterranean fever and recurrent peri-
carditis.
2,3
Preliminary data from nonrandomized
trials have also supported the use of colchicine
for the treatment and prevention of acute pericar-
ditis.
4
In a single-center, open-label, randomized
trial, called the Colchicine for Acute Pericarditis
(COPE) study, the addition of colchicine to con-
ventional therapy with either aspirin or glucocor-
ticoids halved the recurrence rate after an initial
attack of acute pericarditis.
5
Our study, called the
Investigation on Colchicine for Acute Pericarditis
(ICAP), was a randomized, double-blind, placebo-
controlled, multicenter trial designed to evalu-
ate the efficacy and safety of colchicine to treat a
first attack of acute pericarditis and to prevent
recurrences.
6
Methods
Study Design
The rationale, design, and methods of the study
have been reported previously.
6
The trial was de-
signed by the first author, and the design was
approved by the steering committee and the ethics
committee at each participating center. The data
were gathered by all authors and were received,
checked, and analyzed at the cardiology depart-
ment of Maria Vittoria Hospital, Turin, Italy, af-
ter blinded adjudication of events. The first draft
of the manuscript was written by the first author
and revised by all authors. All the authors vouch
for the accuracy and completeness of the data and
the analyses and for the fidelity of this report to
the trial protocol, available with the full text of
this article at NEJM.org.
The study was supported by former Azienda
Sanitaria Locale 3 of Turin (now Azienda Sanitaria
Locale 2). Acarpia (Madeira, Portugal) provided
colchicine and placebo as an unrestricted grant
and had no role in the planning of the study,
analysis of the data, or writing of this manuscript.
Eligibility Criteria
The study was conducted at five general hospitals
in Northern Italy. Consecutive patients who were
18 years of age or older with a first episode of
acute pericarditis (idiopathic, viral, after cardiac
injury, or associated with connective-tissue disease)
were eligible for enrollment. Acute pericarditis
was diagnosed with at least two of the following
criteria: typical chest pain (sharp and pleuritic,
improved by sitting up and leaning forward), a
pericardial friction rub, suggestive changes on
electrocardiography (widespread ST-segment eleva-
tion or PR depression), and new or worsening
pericardial effusion.
7-13
Exclusion Criteria
Patients with any of the following criteria were
not eligible to participate in the trial: tuberculous,
neoplastic, or purulent pericarditis; severe liver
disease or current aminotransferase levels of more
than 1.5 times the upper limit of the normal range;
a serum creatinine level of more than 2.5 mg per
deciliter (221 μmol per liter); skeletal myopathy
or a serum creatine kinase level above the upper
limit of the normal range; blood dyscrasia; inflam-
matory bowel disease; hypersensitivity to colchi-
cine or other contraindication to its use; current
treatment with colchicine; and life expectancy of
18 months or less. Pregnant or lactating women
or women of childbearing potential who were not
protected by a contraception method were also in-
eligible, as were patients with evidence of myoperi-
carditis, as indicated by an elevation in the serum
troponin level.
13
All patients provided written in-
formed consent.
Randomization and Study-Drug Administration
Patients were randomly assigned to receive col-
chicine or placebo in a 1:1 ratio with the use of a
central computer-based automated sequence. Ran-
domization was based on permuted blocks, with
a block size of four. The random-assignment se-
quence was implemented with the use of sequen-
tially numbered study-drug containers. All patients
and investigators were unaware of study-group
assignments.
Colchicine was administered at a dose of 0.5 to
1.0 mg daily for 3 months. The duration of colchi-
cine therapy was based on previous studies (a small,
nonrandomized study and an open-label, single-
center trial).
4,5
The lower dose (0.5 mg daily) was
given to patients weighing 70 kg or less and to
those who had side effects at the higher dose
(0.5 mg twice daily). Colchicine tablets contained
1 mg of the active drug. All tablets (colchicine
and placebo) were identical in color, shape, and
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A Trial of Colchicine for Acute Pericarditis
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3
taste and were premarked to allow splitting into
two equal parts. Adherence to study-drug therapy
was assessed on the basis of counts of pills in
dispensed boxes, with a target of at least 80%
adherence.
All patients also received conventional treat-
ment for acute pericarditis. For most patients, this
consisted of either 800 mg of aspirin or 600 mg
of ibuprofen given orally every 8 hours for 7 to
10 days, followed by tapering during a period of
3 to 4 weeks. Glucocorticoid therapy (0.2 to 0.5 mg
of prednisone per kilogram of body weight per day
for 2 weeks with gradual tapering)
14
was admin-
istered to patients with contraindications to aspi-
rin and ibuprofen (i.e., allergy, history of peptic
ulcer or gastrointestinal bleeding, or use of oral
anticoagulant therapy when the bleeding risk was
considered high or unacceptable) or a history of
side effects. All patients received a proton-pump
inhibitor for gastroduodenal prophylaxis.
10-12
Follow-up and Outcomes
We followed all patients for at least 18 months
after enrollment. Regular visits were planned at
1 week, 1 month, 3 months, 6 months, 12 months,
and every 6 months thereafter until the end of
the study. Testing at each visit included blood
chemical analyses (C-reactive protein, aminotrans-
ferases, creatinine, and creatine kinase), a com-
plete blood count, an electrocardiogram, and an
echocardiogram.
The primary study end point was incessant or
recurrent pericarditis. Secondary end points were
symptom persistence at 72 hours, remission within
1 week, number of recurrences, the time to the
first recurrence, disease-related hospitalization,
cardiac tamponade, and constrictive pericarditis.
A clinical-end-point committee whose members
were unaware of study-group assignments adju-
dicated all events.
Criteria for the diagnosis of recurrent pericar-
ditis included a documented first attack of acute
pericarditis, according to previously stated diag-
nostic criteria; a symptom-free interval of 6 weeks
or longer; and evidence of subsequent recurrence
of pericarditis. Patients with persistent pericar-
ditis or those with a symptom-free interval of less
than 6 weeks were given the diagnosis of inces-
sant pericarditis.
15
Recurrence was documented
by recurrent pain and one or more of the follow-
ing signs: a pericardial friction rub, changes on
electrocardiography, echocardiographic evidence
of pericardial effusion, and an elevation in the
white-cell count, erythrocyte sedimentation rate,
or C-reactive protein level.
16
These criteria for
recurrent pericarditis are based on previous
studies, reviews, and expert opinion.
5,12,13,16
Pa-
tients were considered to have a remission when
they were symptom-free with disappearance of
clinical, electrocardiographic, and echocardio-
graphic signs of disease.
11,12,16
Data Management
Investigators who were unaware of study-group
assignments collected data using case-report and
clinical-events forms, with adjudication by the
clinical-end-point committee. During follow-up,
240 Underwent randomization
280 Patients were assessed for eligibility
40 Were excluded
11 Had cancer
5 Were <18 yr of age
5 Had evidence of pul-
monary tuberculosis
5 Declined to participate
4 Had elevated amino-
transferase level
4 Had elevated serum
creatinine level
3 Were pregnant
2 Were receiving colchicine
for other medical condition
1 Had elevated serum
creatine kinase level
120 Were assigned to colchicine 120 Were assigned to placebo
14 Discontinued colchicine 12 Discontinued placebo
120 Were included in the analysis
120 Were included in the analysis
Figure 1. Enrollment and Outcomes.
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all adverse events were monitored and recorded.
Unblinded data were made available to an inde-
pendent data and safety monitoring board.
Statistical Analysis
We assumed a rate of incessant or recurrent peri-
carditis of 30% in the placebo group at 18
months
5,16
and estimated that colchicine could re-
duce the proportion of patients with incessant or
recurrent pericarditis by half. With a two-sided
alpha level of 0.05, a total enrollment of 240 pa-
tients was needed to attain a power of 80% to de-
tect an absolute reduction of 15 percentage points
in the proportion of patients with incessant or re-
current pericarditis in the colchicine group.
All analyses were performed on the basis of the
intention-to-treat principle. Data were expressed
as means and standard deviations. We used the
Mann–Whitney test for continuous variables and
the chi-square test for categorical variables. A
two-sided P value of less than 0.05 was consid-
ered to indicate statistical significance. We used
the Kaplan–Meier method to estimate time-to-
event distributions, which were compared with
the use of the log-rank test. Analyses were per-
formed with SPSS software, version 13.0.
Results
Patients
Enrollment started in August 2005 and ended in
December 2010. Follow-up continued through
June 2012, with a predetermined stopping point
providing a minimum of 18 months of follow-up
for the primary outcome.
Study enrollment, randomization, and reten-
tion are shown in Figure 1. Of the 280 patients
who were screened, 240 (85.7%) were enrolled;
120 patients were randomly assigned to each of
the two study groups. The baseline demographic
and clinical characteristics of the patients were
similar in the two groups (
Table 1
). The mean
age of the patients was 52.1±16.9 years, and 60%
were male. Clinical signs and symptoms were
consistent with previous findings from published
unselected series of patients with acute pericar-
ditis.
7-9
There was more than 95% adherence to the
study-drug regimen before the primary outcome
was reached or the study was completed, and
adherence rates did not differ significantly be-
tween the two study groups. All patients who
tolerated treatment with colchicine or placebo
discontinued therapy at 3 months, as planned.
No open-label colchicine was administered after
the end of the study period. No patient was lost
to follow-up, and all patients were analyzed for
outcomes according to the original study-group
assignments. Patients were followed for an aver-
age of 22 months.
Outcomes
The main outcome results are reported in
Table 2
.
The primary outcome of incessant or recurrent
pericarditis occurred in 20 patients (16.7%) in
the colchicine group and in 45 patients (37.5%) in
the placebo group (relative risk reduction in the
colchicine group, 0.56; 95% confidence interval
[CI], 0.30 to 0.72; P<0.001). The number of pa-
tients who would need to have been treated to
Table 1. Characteristics of the Patients at Baseline.*
Characteristic
Placebo
(N = 120)
Colchicine
(N = 120)
Age — yr 50.7±17.5 53.5±16.2
Male sex — no. (%) 74 (61.7) 71 (59.2)
Cause of pericarditis — no. (%)
Idiopathic 93 (77.5) 92 (76.7)
Post–cardiac injury syndrome 23 (19.2) 25 (20.8)
Connective-tissue disease† 4 (3.3) 3 (2.5)
Clinical findings — no. (%)
Pericarditic chest pain 119 (99.2) 120 (100.0)
Pericardial rub 38 (31.7) 44 (36.7)
ST-segment elevation 26 (21.7) 35 (29.2)
Pericardial effusion‡ 82 (68.3) 76 (63.3)
Mild (<10 mm) 76 (63.3) 64 (53.3)
Moderate (10–20 mm) 2 (1.7) 9 (7.5)
Large (>20 mm) 4 (3.3) 3 (2.5)
Cardiac tamponade 2 (1.7) 2 (1.7)
Elevated C-reactive protein level 89 (74.2) 85 (70.8)
Medications — no. (%)
Aspirin 96 (80.0) 86 (71.7)
Ibuprofen 18 (15.0) 24 (20.0)
Prednisone 6 (5.0) 10 (8.3)
* Plus–minus values are means ±SD. There were no significant differences be-
tween the two groups.
Included in the category of connective-tissue disease are systemic lupus ery-
thematosus in 4 patients, Sjögren’s syndrome in 2 patients, and rheumatoid
arthritis in 1 patient.
Pericardial effusion was mild in 105 of 185 patients (56.8%) with an idiopathic
cause of pericarditis and in 35 of 55 patients (64%) with other causes. Moder-
ate or large effusions occurred in 14 of 185 patients (7.6%) with an idiopathic
cause and in 4 of 55 patients (7%) with other causes.
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A Trial of Colchicine for Acute Pericarditis
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prevent one case of incessant or recurrent peri-
carditis was 4. The recurrence rate was 9.2% in
the colchicine group and 20.8% in the placebo
group (relative risk reduction, 0.56; 95% CI, 0.13
to 0.99; P = 0.02; number needed to treat, 9). Ka-
plan–Meier survival curves for freedom from in-
cessant or recurrent pericarditis are shown in
Figure 2. Results were similar regardless of
whether the concomitant antiinflammatory ther-
apy was aspirin or ibuprofen (
Table 2
).
Colchicine also reduced the frequency of symp-
tom 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 rate of hospital-
ization related to pericarditis (5.0% vs. 14.2%,
P = 0.02). Colchicine also improved the rate of re-
mission within 1 week (85.0% vs. 58.3%, P<0.001)
and prolonged the time to first recurrence (24.7
weeks vs. 17.7 weeks, P<0.001). In multivariable
analysis, independent risk factors for recurrenc-
es were the use of glucocorticoids (odds ratio,
4.17; 95% CI, 1.28 to 13.53; P = 0.02) and C-reac-
tive protein elevation at presentation (odds ratio,
3.15; 95% CI, 1.05 to 9.49; P = 0.04).
Adverse Events
The incidence and type of adverse events are re-
ported in
Table 3
. The overall rates of adverse
events were similar in the two study groups
(11.7% in the colchicine group and 10.0% in the
placebo group, P = 0.84). Rates of study-drug dis-
continuation were also similar in the two groups
(11.7% and 8.3%, respectively; P = 0.52). A medi-
cal decision was the main cause of study-drug
discontinuation in 21 of 24 patients (87.5%).
No serious adverse events were observed.
Gastrointestinal disturbance was the main side
effect and was reported with similar frequency
in the two groups (9.2% in the colchicine group
and 8.3% in the placebo group, P = 0.67).
Discussion
In this multicenter, double-blind, randomized
trial, the use of colchicine in addition to conven-
tional antiinflammatory therapy significantly
reduced the rate of incessant or recurrent peri-
carditis, reduced the number of recurrences of
pericarditis, and prolonged the time to recurrence,
as compared with placebo. Most of the study pa-
tients were treated with aspirin and a smaller
number with ibuprofen, and the results were con-
sistent regardless of the concomitant background
antiinflammatory therapy. Diarrhea was the ma-
jor limiting side effect associated with colchicine
and was reported in less than 10% of patients,
and no serious adverse events were recorded.
The exact mechanism of benefit of colchicine
in patients with pericarditis is not fully under-
stood. The therapeutic effect seems to be related
Table 2. Trial Outcomes.*
Outcome
Placebo
(N = 120)
Colchicine
(N = 120) P Value
Incessant or recurrent pericarditis: primary end point
— no. (%)‡
45 (37.5) 20 (16.7) <0.001†
Symptom persistence at 72 hr — no. (%) 48 (40.0) 23 (19.2) 0.001
Remission at 1 wk — no. (%) 70 (58.3) 102 (85.0) <0.001
Incessant course — no. (%) 20 (16.7) 9 (7.5) 0.046
Recurrent course — no. (%) 25 (20.8) 11 (9.2) 0.02
No. of recurrences per patient 0.52±0.81 0.21±0.52 0.001
Time to first recurrence — wk 17.7±9.0 24.7±11.0 <0.001
Cardiac tamponade — no. (%) 3 (2.5) 0 0.25
Constrictive pericarditis — no. (%) 1 (0.8) 0 1.00
Pericarditis-related hospitalization — no. (%) 17 (14.2) 6 (5.0) 0.02
Mean follow-up — mo 22.3±8.7 22.9±8.7 0.61
* Plus–minus values are means ±SD.
The P value was calculated by means of the log-rank test.
The type of background antiinflammatory therapy had no significant effect on the proportions of patients with inces-
sant or recurrent pericarditis.
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to its ability to disrupt microtubules and to con-
centrate in leukocytes, especially granulocytes,
where its peak concentration may be more than
16 times the peak concentration in plasma, even at
low oral doses, such as those used in this trial.
2,17
Colchicine was recommended as a first-line
treatment for recurrent pericarditis (class I indi-
cation) in the 2004 guidelines of the European
Society of Cardiology regarding the management
of pericardial diseases
18
on the basis of small,
nonrandomized studies and on expert consensus.
In 2005, an open-label, randomized trial, the Col-
chicine for Recurrent Pericarditis (CORE) study,
showed a benefit of colchicine in the treatment
of recurrent pericarditis.
19
This was followed by
the report of the multicenter, double-blind Col-
chicine for Recurrent Pericarditis (CORP) trial
16
and a subsequent meta-analysis
3
supporting the
use of colchicine in such patients.
These trials, however, did not address the use
of colchicine for the initial attack of acute peri-
carditis. Among such patients, the cause of the
disease is different from recurrent pericarditis.
There is evidence that cases of recurrent pericar-
ditis are immune-mediated, and colchicine may
help to disrupt the inflammatory cycle involved in
its pathogenesis.
20,21
In contrast, acute pericar-
ditis often has an infectious cause that is pre-
sumed to be viral in most patients in developed
countries.
10-12,22
In such cases, the interference
of colchicine with white-cell function may theo-
retically be deleterious for the clearance of the
infectious agent. Given these differences in patho-
genesis, the efficacy and safety of colchicine in
acute pericarditis require separate confirmation.
The 2004 European guidelines gave the use of
colchicine in acute pericarditis a class IIa indica-
tion.
18
The subsequent COPE trial was a single-
center, open-label, randomized trial that suggested
a benefit of colchicine in acute pericarditis.
5
Our
study now confirms these preliminary findings
with the stronger evidence provided by a multi-
center, double-blind trial and a larger number of
cases.
Current guidelines recommend colchicine dos-
es of 2 mg per day for 1 to 2 days, followed by a
maintenance dose of 1 mg per day.
18
However,
lower doses may improve patient compliance and
be equally efficacious. The COPE, CORE, and
CORP trials used a maintenance dose of 0.5 mg
twice daily, which was reduced to 0.5 mg daily in
patients weighing less than 70 kg. In our study,
a loading dose was not given, and patients had
similar side effects in the colchicine and placebo
groups, a finding that supports the use of a
Probability of Event-free Survival
1.0
0.8
0.9
0.7
0.6
0.4
0.3
0.1
0.5
0.2
0.0
0 963 12 15
18
Months
No. at Risk
Colchicine
Placebo
120
120
105
87
105
80
102
78
102
78
98
75
89
69
P<0.001 by log-rank test
Placebo
Colchicine
Figure 2. KaplanMeier Survival Curves for Freedom from Incessant
or Recurrent Pericarditis (Primary Outcome).
Table 3. Adverse Events.
Adverse Event
Placebo
(N = 120)
Colchicine
(N = 120) P Value
no. (%)
Overall 12 (10.0) 14 (11.7) 0.84
Gastrointestinal disorder* 10 (8.3) 11 (9.2) 0.67
Hepatotoxicity† 1 (0.8) 2 (1.7)
Myotoxicity 0 0
Alopecia 1 (0.8) 1 (0.8)
Other 0 0
Serious adverse event‡ 0 0
Drug discontinuation 10 (8.3) 14 (11.7) 0.52
Physician decision 9 (7.5) 12 (10.0)
Patient decision 1 (0.8) 2 (1.7)
* Gastrointestinal disorders included diarrhea, nausea, cramping, abdominal
pain, and vomiting.
Hepatotoxicity was defined as an elevation in aminotransferase levels above
the normal reference range.
Adverse events were considered to be serious if they were fatal or life-threat-
ening, required hospitalization, or resulted in substantial or permanent dis-
ability or a medically significant event (i.e., one that could have jeopardized
the patient or required medical or surgical intervention to prevent an adverse
outcome).
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weight-adjusted maintenance dose without any
loading dose.
A number of limitations of our study should be
considered. Our findings might not be generaliz-
able to other clinical conditions or other patient
populations; in this regard, we excluded patients
with elevated levels of aminotransferases, creati-
nine, or troponin and those with liver disease,
myopathy, blood dyscrasias, or inflammatory
bowel disease. Our results should not be applied
to women who are pregnant or lactating or to
children. We also excluded patients with bacterial
or neoplastic pericarditis. Of note, colchicine is
not approved for the prevention of recurrent peri-
carditis in North America or Europe, and its use
as such is off-label. Our limited sample size might
have precluded the identification of rare adverse
effects. Further research is needed to identify the
best duration of colchicine treatment, since we
selected the arbitrary treatment length of 3 months
on the basis of previous studies,
3-5
and we specu-
late that a longer duration might further decrease
the 9 to 10% recurrence rate.
In conclusion, we conducted a randomized trial
of colchicine versus placebo, in addition to con-
ventional antiinflammatory therapy, in patients
with a first episode of acute pericarditis. Colchi-
cine reduced the rate of incessant or recurrent
pericarditis in these patients, as compared with
placebo.
Supported by Azienda Sanitaria Locale 3 of Turin and Acarpia.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
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    • "It is postulated that hyperuricemia can have effect on the inflammatory and fibrotic process [34] leading to an increased atrial size and eventually AF [32] which may occur with or without a preceding inflammatory process. Some studies showed that treatment of hyperuricemia can prevent inflammatory and fibrosis formation in certain disease such as pericarditis [35, 36]. Results of our study have some clinical implications. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Atrial fibrillation (AF) is a common cardiac arrhythmia and increases risk of ischemic stroke. Data on the prevalence of AF in Thailand is lacking especially in patients with hypertension. The objectives of this study were to determine prevalence of AF in patients with hypertension and to determine factors that are associated with increased prevalence of AF in a multicenter nationwide study. Methods A cross-sectional survey for the national outcome evaluation among hypertensive patients visiting 831 public hospitals in Thailand was conducted between 2011 and 2012 to evaluate status of standard care in hypertensive patients visiting public Thailand Ministry of Public Health (MoPH) hospitals. Inclusion criteria were hypertensive patients aged at least 20 years who had received medical care in the targeted hospital for at least 12 months. The main outcome measurement was AF rhythm, and was measured along with potential risk factors age, gender and cardiovascular risk factors. Results There were 13207 hypertensive patients who had ECG data recorded during the survey. AF was detected in 457 patients (3.46 %). Prevalence of AF increased with increasing age, was more common in males and in patients with chronic kidney disease (CKD). Multivariable modelling was conducted to assess which factors were most associated with increased prevalence of AF, and the results showed older age followed by male gender, low LDL-cholesterol and increased uric acid levels were the most important risk factors for AF in this population. Conclusions Prevalence of AF in hypertensive patients was 3.46 %. Factors associated with increased risk of AF are old age, male gender, low LDL-cholesterol and elevated uric acid level.
    Full-text · Article · Dec 2016 · BMC Cardiovascular Disorders
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    • "Those NSAIDs with the most evidence for treating IP have similar pharmacokinetic profiles [18]. NSAIDs, in general, are well absorbed, possess a relatively narrow volume of distribution, are highly protein bound, and undergo minimal first-pass hepatic metabolism [18]. NSAIDs differ in their half-life and potency. "
    [Show abstract] [Hide abstract] ABSTRACT: Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician's understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy.
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  • [Show abstract] [Hide abstract] ABSTRACT: We review some of the most influential papers from 2012 in the different aspects of emergency medicine, such as prehospital medicine, resuscitation, early diagnosis and timely ED discharge and treatment. In particular, intramuscular benzodiazepines have been shown to be efficient in prehospital status epilepticus, epinephrines usefulness in cardiopulmonary resuscitation has been challenged, colloids have been shown to be deleterious in the treatment of severe sepsis and septic shock, the time window for thrombolysis in acute stroke will probably be extended, acute pyelonephritis treatment duration can be decreased, new D-dimers thresholds for older patients may prevent further diagnosis tests, and hs-Troponin may allow earlier discharge of low coronary risk patients.
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