Clinician Update
Treatment of Acute and Recurrent Idiopathic Pericarditis
Leonard S. Lilly, MD
C ase Presentation: A 56-year-old
Downloaded from http://circ.ahajournals.org/ by guest on July 1, 2018
previously healthy man presented
with 2 days of pleuritic left anterior
chest pain, lessened by sitting forward.
His examination was pertinent for low-
grade fever (37.6°C), blood pressure
122/76 mm  Hg without paradox, no
jugular venous distension, clear lungs,
and a 3-component pericardial friction
rub. The ECG showed diffuse concave-
upward ST-segment elevation and
PR-segment depression in the inferior
leads. The serum C-reactive protein level
was 64 mg/L, and the cardiac troponin
T was not elevated. Echocardiography
showed normal left ventricular contrac-
tile function without wall motion abnor-
malities and no pericardial effusion. He
was diagnosed with acute pericarditis,
and the symptoms responded promptly
to oral ibuprofen, continued for 2 weeks.
Six weeks later, he redeveloped pleuritic
chest pain and clinical and ECG findings
identical to the initial presentation. His
primary care physician asks for advice
about appropriate therapy.
Background
Pericarditis accounts for 5% of emer-
gency department visits for chest pain
in the absence of myocardial infarc-
tion.1 In ≈80% of cases in developed
countries, the cause of pericarditis is
either postviral or “idiopathic,” in that
From the Cardiovascular Division, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.
Correspondence to Leonard S. Lilly, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail
llilly@partners.org
(Circulation. 2013;127:1723-1726.)
© 2013 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
it cannot be attributed to a specific
condition.2,3 Because these 2 etiologies
are clinically equivalent, the term idio-
pathic pericarditis will refer to both in
this Clinician Update. Even when man-
aged effectively, many patients with
acute pericarditis present with 1 or
more repeated episodes, termed recur-
rent pericarditis.4
Acute Pericarditis
Management
Treatment of idiopathic pericarditis
has long been empirical, because until
recently, there have been few therapeu-
tic trials addressing this condition. The
European Society of Cardiology pub-
lished the only treatment guideline for
pericarditis almost a decade ago, and
many of the recommendations were
based on opinion because of the lack of
available study evidence.4
Most patients with idiopathic peri-
carditis experience self-limited symp-
toms that improve spontaneously within
days to weeks. More rapid relief can be
achieved with pharmacological interven-
tion, and stable patients can be managed
in the outpatient setting. Hospitalization
is recommended when features suggest
nonidiopathic causes or herald hemo-
dynamic compromise, including fever
>38°C (>100.4°F), the subacute devel-
opment of symptoms (characteristic of
DOI: 10.1161/CIRCULATIONAHA.111.066365
1723
tuberculosis, neoplastic disease, uremia,
or collagen vascular disorders), hypo-
tension, jugular venous distension, a
large pericardial effusion, or echocar-
diographic features of impending tam-
ponade (Figure).5,6 Patients who are
immunocompromised or are undergoing
therapy with anticoagulants should also
be observed initially in the hospital.5
Pharmacological Treatment
Effective agents include nonsteroidal
anti-inflammatory drugs (NSAIDs),
colchicine, and glucocorticoids. Con-
currently, rest and avoidance of demand-
ing physical activity help to minimize
symptoms.
Nonsteroidal Anti-inflammatory
Drugs
Aspirin and other NSAIDs are the
first-line approach, based on clinical
experience and observational reports.5,7
For example, in a 2004 study without
a control group, outpatient therapy of
uncomplicated pericarditis with aspi-
rin relieved symptoms in 87% of 254
patients.5 Commonly used NSAID
regimens are listed in the Table, with
a recommended initial duration of 7
to 14 days, then treatment should be
tapered until resolution of symptoms
and improvement of acutely elevated
serum inflammatory markers such as
C-reactive protein and the erythrocyte
 1724  Circulation  April 23, 2013

Table. Pharmacological Treatment of Idiopathic Pericarditis pericarditis over the subsequent 18

months was 32.3% in the aspirin group
Medication Dosage Duration of Therapy
but only 10.7% in those who received
Nonsteroidal anti-inflammatory drugs colchicine plus aspirin (P=0.004). In
 Aspirin PO: 650–975 mg 3–4 times daily 1–2 wk (2–4 wk for addition, whereas 36.7% of patients
recurrence) in the aspirin group were still symp-
 Ibuprofen PO: 400–800 mg 3 times daily 1–2 wk (2–4 wk for tomatic at 72 hours after presentation,
recurrence) only 11.7% of those who also received
 Indomethacin PO: 50 mg 3 times daily 1–2 wk (2–4 wk for colchicine remained symptomatic
recurrence) (P=0.003).
 Ketorolac IM: 30–60 mg once, or 15–30 mg every Should not exceed 5 days Long-term low-dose colchicine is
6 h, or IV: 15–30 mg every 6 h well tolerated, requiring discontinu-
Colchicine 0.5 or 0.6 mg 2 times daily* Up to 3 mo (Up to 6 mo ation only rarely, primarily for diar-
for recurrence) rhea.12 Uncommon serious side effects,
Prednisone 0.25–0.5 mg/kg/d for 2 wk (2–4 wk for recurrence), then: occurring primarily in patients with
At dose of: Taper by†: chronic renal insufficiency, include
Downloaded from http://circ.ahajournals.org/ by guest on July 1, 2018

25–50 mg daily 5–10 mg every 1–2 wk hepatic toxicity and myelosuppression.

15–25 mg daily 2.5 mg every 2–4 wk It is now common practice to include
<15 mg daily 1.0–2.5 mg every 2–6 wk
colchicine, in combination with an
NSAID, as initial management of acute
IM indicates intramuscular administration; IV, intravenous administration; and PO, by mouth.
idiopathic pericarditis (Table).
*Reduced dosage recommended for patients with advanced renal dysfunction or concurrent therapy with
moderate to strong inhibitors of CYP3A4 (eg, protease inhibitors, ketoconazole, fluconazole, erythromycin, Glucocorticoids
diltiazem, verapamil) or P-glycoprotein inhibitors (eg, cyclosporine). Steroid therapy has long been used to
†As recommended by Imazio et al.2
treat pericarditis because it induces
prompt symptomatic relief; however,
sedimentation rate. Because high 61% of those with symptoms who did glucocorticoids should not be used
doses are often required, consideration not respond by 7 days of therapy were as primary therapy in uncomplicated
should also be given to gastric protec- ultimately found not to have idiopathic acute idiopathic pericarditis because of
tion therapy (eg, a proton pump inhibi- pericarditis. Forty-three percent were a high rate of relapse when the steroid
tor or misoprostol5). determined to have autoimmune condi- is tapered or stopped.4,12,13 Glucocorti-
No single NSAID appears to be tions, and 18% had tuberculosis.5 coids also appear to blunt the efficacy
more effective than another in acute of colchicine in preventing recur-
pericarditis, and in addition to oral Colchicine rences.14 As a result, and owing to the
agents, the parenteral NSAID ketorolac On the basis of its anti-inflammatory side effects associated with long-term
was shown to rapidly relieve symptoms effectiveness in the serositis of famil- steroid therapy, glucocorticoids should
in an uncontrolled trial.8 Aspirin is the ial Mediterranean fever, colchicine only be prescribed to patients with
preferred anti-inflammatory agent for therapy for pericarditis was initially idiopathic pericarditis who are refrac-
patients with pericarditis after myocar- described in small observational tory to treatment with, or intolerant of,
dial infarction because other NSAIDs reports >2 decades ago.11 Consensus an NSAID plus colchicine.4
have delayed infarct healing in animal opinion in the 2004 European Society When used, the prednisone dosage
models9 and are associated with an of Cardiology guidelines listed colchi- recommended in the 2004 European
increased risk of future coronary events cine as effective in recurrent pericardi- Society of Cardiology guidelines was
in this population.10 tis, and probably in acute pericarditis, a relatively high 1.0 mg·kg−1·d−1 for
A rapid response to aspirin or other for which it was assigned a class IIa 2 weeks with rapid tapering. A lower
NSAID therapy predicts a favorable indication.4 Subsequent prospective tri- dosage (0.25–0.50 mg·kg−1·d−1) for 2
prognosis in acute pericarditis and als have provided additional evidence. to 4 weeks, followed by slow tapering
an unlikely progression to complica- In the open-label Colchicine in Acute (Table) is effective and is associated
tions such as pericardial constriction.3 Pericarditis (COPE) trial, 120 patients with fewer relapses than the higher
However, if chest discomfort or fever with a first episode of acute pericarditis dosage.15
persists >1 week, or a new or larger peri- were randomized to receive colchicine
cardial effusion develops during therapy, (0.5–1.0 mg daily for 3 months after Recurrent Pericarditis
a cause of pericarditis other than postvi- 1–2 mg on the first day) plus aspirin Management
ral/idiopathic should be suspected. In the (800 mg every 6–8 hours for 7–10 One or more recurrences arise in 15% to
report of 254 patients with acute pericar- days, then tapered over 3–4 weeks) or 30% of patients after an initial episode
ditis treated as outpatients with aspirin, aspirin alone.12 The rate of recurrent of acute pericarditis.2 These attacks can

Clinical Presentation of Acute Pericarditis
• Pleuritic, positional chest pain
• Pericardial rub
• ECG abnormalities
• ± Pericardial effusion on imaging
High-risk
Features
• Fever > 38°C
• Subacute onset
Downloaded from http://circ.ahajournals.org/ by guest on July 1, 2018
• Anticoagulated
• Immunocompromised
• Hypotension
• Jugular venous
distension
• Large effusion
No
Outpatient Management
• NSAID x 2 weeks
• ± Colchicine x 3 months
Figure.  Initial triage pathway in acute pericarditis. NSAID indicates nonsteroidal anti-
inflammatory drug.
repeat over extended periods of time and
may lead to substantial disability. A first
recurrence typically presents within 18
months, and findings are similar to the
initial episode, including pleuritic chest
pain, diffuse ST-segment elevations,
a pericardial friction rub, and elevated
serum markers of inflammation.16
Pharmacological Treatment
Nonsteroidal Anti-inflammatory
Drugs
In the absence of prospective trial
evidence, aspirin or another NSAID
should form the foundation of therapy
for recurrences (Table).4 However, in
contrast to the brief course of NSAID
generally prescribed for an initial
Lilly   Acute and Recurrent Idiopathic Pericarditis  1725
Yes
Admit to
Hospital
episode, a gradual tapering of the drug
over 2 to 4 weeks after symptoms
improve is recommended.16
Colchicine
Use of colchicine in the COPE trial
was associated with fewer initial peri-
carditis recurrences.12 Additionally, the
Colchicine for Recurrent Pericarditis
(CORE) trial randomized 84 patients
who had already had a first recurrence
to aspirin or aspirin plus colchicine.16
Compared with aspirin alone, the com-
bination reduced the rate of additional
recurrences by 50%.
Most recently, the double-blinded
Colchicine for Recurrent Pericarditis
(CORP) trial randomized 120 patients
with a first recurrence to colchicine
or placebo, in addition to aspirin or
another NSAID.17 The rate of subse-
quent recurrence was 24% in those
randomized to colchicine compared
with 55% in the placebo group. In
addition, the mean number of episodes
was reduced and the time to next recur-
rence was lengthened. The duration of
colchicine therapy in the CORE and
CORP trials for recurrent pericarditis
was 6 months.
Glucocorticoids
Symptoms of pericarditis recurrence
respond promptly to glucocorticoid
therapy.1 However, when administered
in this situation, slow tapering and a
prolonged course may be required to
prevent recrudescent symptoms, with
the potential for long-term steroid-
associated side effects. Furthermore,
the risk of additional recurrences of
pericarditis is augmented by steroid
use.12,14,16 Therefore, the consensus is
to initially treat recurrent episodes of
pericarditis with an NSAID plus col-
chicine and to prescribe glucocorti-
coids only for refractory cases.
Patients sometimes present with
chest discomfort reminiscent of prior
pericarditis, which is interpreted as
a recurrence, even in the absence of
objective findings (no pericardial rub,
ECG or echocardiographic abnormali-
ties, or elevation of serum inflamma-
tory markers). Although a trial of an
NSAID plus colchicine may be reason-
able in this situation, glucocorticoids
should certainly be avoided.18
Imazio and colleagues15 compared
2 steroid dosage intensities in recur-
rent pericarditis: Prednisone 0.2 to 0.5
mg·kg−1·d−1 versus the higher com-
monly used dose of 1.0 mg·kg−1·d−1
for 4 weeks, followed by a slow taper.
The lower-dose regimen was effec-
tive, whereas the higher dosage was
associated with more side effects and a
greater number of subsequent pericar-
ditis recurrences and hospitalizations.
Thus, a now common approach to the
use of steroids in patients with recurrent
pericarditis whose symptoms are refrac-
tory to an NSAID plus colchicine is the
lower-dose prednisone regimen listed in
the Table. With prolonged corticosteroid
 1726  Circulation  April 23, 2013
use, osteoporosis prevention (eg, cal-
cium, vitamin D, and bisphosphonates)
should be considered.
A common cause of referral to
specialized pericardial centers is the
inability to taper glucocorticoid ther-
apy below a certain dosage (typically
≈15 mg of prednisone daily) without
reemergence of symptoms, despite
concurrent NSAID plus colchicine
treatment. An often effective strategy
in this circumstance is to resume the
lowest prior steroid dosage that had
controlled symptoms, and then taper it
by only 1 to 2 mg every 2 to 4 weeks.19
Downloaded from http://circ.ahajournals.org/ by guest on July 1, 2018
Other Considerations
For refractory pericarditis despite
NSAID, colchicine, and glucocorti-
coid therapies, improved symptoms
have been reported in small numbers of
patients with the use of immunosuppres-
sive agents (azathioprine or methotrex-
ate), intravenous immunoglobulin, and
the interleukin-1β receptor antagonist
anakinra.2 Finally, pericardiectomy can
be undertaken for symptomatic relief in
cases of continuously relapsing pericar-
ditis.1 Results have been variable, with
some patients experiencing complete
remission but others continuing to be
plagued with ongoing symptoms after
surgical intervention. The best outcomes
have been reported when complete resec-
tion of the pericardium is undertaken.20
Case Presentation
(Continued)
The patient’s recurrent pericarditis was
treated with ibuprofen 600 mg 3 times
daily plus colchicine 0.6 mg twice
daily. Ibuprofen was tapered off after
3 weeks, and the colchicine was con-
tinued for 6 months. After 1 additional
year of follow-up, he has had no further
symptoms of pericarditis.
Summary
Appropriate therapy for acute idio-
pathic pericarditis is an NSAID for ≈2
weeks, and it is also reasonable to pre-
scribe colchicine for up to 3 months (the
duration used in clinical trials), espe-
cially to reduce the rate of recurrence.
For initially refractory symptoms, the
parenteral NSAID ketorolac may be
beneficial. For recurrent episodes of
pericarditis, treatment with an NSAID
plus colchicine is recommended, but
for a more prolonged course. During
NSAID treatment, concurrent gastric
protection therapy should be consid-
ered. Only for truly refractory cases
should glucocorticoid therapy be used.
Disclosures
None.
References
1. Khandaker MH, Espinosa RE, Nishimura
RA, Sinak LJ, Hayes SN, Melduni RM, Oh
JK. Pericardial disease: diagnosis and man-
agement. Mayo Clin Proc. 2010;85:572–593.
2. Imazio M, Spodick DH, Brucato A, Trin-
chero R, Adler Y. Controversial issues in the
management of pericardial diseases. Circula-
tion. 2010;121:916–928.
3. Zayas R, Anguita M, Torres F, Giménez D,
Bergillos F, Ruiz M, Ciudad M, Gallardo A,
Vallés F. Incidence of specific etiology and
role of methods for specific etiologic diagno-
sis of primary acute pericarditis. Am J Car-
diol. 1995;75:378–382.
4. Maisch B, Seferović PM, Ristić AD, Erbel
R, Rienmüller R, Adler Y, Tomkowski WZ,
Thiene G, Yacoub MH; Task Force on the Di-
agnosis and Management of Pericardial Dis-
eases of the European Society of Cardiology.
Guidelines on the diagnosis and management
of pericardial diseases executive summary:
the Task Force on the Diagnosis and Man-
agement of Pericardial Diseases of the Eu-
ropean Society of Cardiology. Eur Heart J.
2004;25:587–610.
5. Imazio M, Demichelis B, Parrini I, Giuggia
M, Cecchi E, Gaschino G, Demarie D, Ghi-
sio A, Trinchero R. Day-hospital treatment
of acute pericarditis: a management program
for outpatient therapy. J Am Coll Cardiol.
2004;43:1042–1046.
6. Imazio M, Cecchi E, Demichelis B, Ierna
S, Demarie D, Ghisio A, Pomari F, Coda
L, Belli R, Trinchero R. Indicators of poor
prognosis of acute pericarditis. Circulation.
2007;115:2739–2744.
7. Schifferdecker B, Spodick DH. Nonsteroidal
anti-inflammatory drugs in the treatment of
pericarditis. Cardiol Rev. 2003;11:211–217.
8. Arunasalam S, Siegel RJ. Rapid resolution
of symptomatic acute pericarditis with ke-
torolac tromethamine: a parenteral nonste-
roidal antiinflammatory agent. Am Heart J.
1993;125(pt 1):1455–1458.
9. Hammerman H, Kloner RA, Schoen FJ,
Brown EJ Jr, Hale S, Braunwald E. Indo-
methacin-induced scar thinning after experi-
mental myocardial infarction. Circulation.
1983;67:1290–1295.
10. Olsen AM, Fosbøl EL, Lindhardsen J, Folke
F, Charlot M, Selmer C, Bjerring Olesen J,
Lamberts M, Ruwald MH, Køber L, Hansen
PR, Torp-Pedersen C, Gislason GH. Long-
term cardiovascular risk of nonsteroidal
anti-inflammatory drug use according to time
passed after first-time myocardial infarc-
tion: a nationwide cohort study. Circulation.
2012;126:1955–1963.
11. Adler Y, Finkelstein Y, Guindo J, Rodriguez
de la Serna A, Shoenfeld Y, Bayes-Genis A,
Sagie A, Bayes de Luna A, Spodick DH.
Colchicine treatment for recurrent pericar-
ditis: a decade of experience. Circulation.
1998;97:2183–2185.
12. Imazio M, Bobbio M, Cecchi E, Demarie D,
Demichelis B, Pomari F, Moratti M, Gaschino
G, Giammaria M, Ghisio A, Belli R, Trinche-
ro R. Colchicine in addition to conventional
therapy for acute pericarditis: results of the
COlchicine for acute PEricarditis (COPE)
trial. Circulation. 2005;112:2012–2016.
13. Lotrionte M, Biondi-Zoccai G, Imazio M,
Castagno D, Moretti C, Abbate A, Agostoni
P, Brucato AL, Di Pasquale P, Raatikka M,
Sangiorgi G, Laudito A, Sheiban I, Gaita F.
International collaborative systematic review
of controlled clinical trials on pharmacologic
treatments for acute pericarditis and its recur-
rences. Am Heart J. 2010;160:662–670.
14. Artom G, Koren-Morag N, Spodick DH,
Brucato A, Guindo J, Bayes-de-Luna A,
Brambilla G, Finkelstein Y, Granel B, Bayes-
Genis A, Schwammenthal E, Adler Y. Pre-
treatment with corticosteroids attenuates the
efficacy of colchicine in preventing recurrent
pericarditis: a multi-centre all-case analysis.
Eur Heart J. 2005;26:723–727.
15. Imazio M, Brucato A, Cumetti D, Brambilla
G, Demichelis B, Ferro S, Maestroni S, Cec-
chi E, Belli R, Palmieri G, Trinchero R. Cor-
ticosteroids for recurrent pericarditis: high
versus low doses: a nonrandomized observa-
tion. Circulation. 2008;118:667–671.
16. Imazio M, Bobbio M, Cecchi E, Demarie D,
Pomari F, Moratti M, Ghisio A, Belli R, Trin-
chero R. Colchicine as first-choice therapy
for recurrent pericarditis: results of the CORE
(COlchicine for REcurrent pericarditis) trial.
Arch Intern Med. 2005;165:1987–1991.
17. Imazio M, Brucato A, Cemin R, Ferrua S,
Belli R, Maestroni S, Trinchero R, Spodick
DH, Adler Y; CORP (COlchicine for Recur-
rent Pericarditis) Investigators. Colchicine for
recurrent pericarditis (CORP): a randomized
trial. Ann Intern Med. 2011;155:409–414.
18. Imazio M, Demichelis B, Parrini I, Cecchi E,
Pomari F, Demarie D, Gaschino G, Ghisio A,
Belli R, Trinchero R. Recurrent pain without
objective evidence of disease in patients with
previous idiopathic or viral acute pericarditis.
Am J Cardiol. 2004;94:973–975.
19. Brucato A, Brambilla G, Adler Y, Spodick
DH, Canesi B. Therapy for recurrent acute
pericarditis: a rheumatological solution? Clin
Exp Rheumatol. 2006;24:45–50.
20. Khandaker MH, Schaff HV, Greason KL,
Anavekar NS, Espinosa RE, Hayes SN,
Nishimra RA, Oh JK. Pericardiectomy vs med-
ical management in patients with relapsing peri-
carditis. Mayo Clin Proc. 2012;87:1062–1070.
Key Words: colchicine ◼ drug therapy
◼ pericarditis
 Treatment of Acute and Recurrent Idiopathic Pericarditis
Leonard S. Lilly

Circulation. 2013;127:1723-1726
doi: 10.1161/CIRCULATIONAHA.111.066365
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Downloaded from http://circ.ahajournals.org/ by guest on July 1, 2018

Copyright © 2013 American Heart Association, Inc. All rights reserved.

Print ISSN: 0009-7322. Online ISSN: 1524-4539

The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circ.ahajournals.org/content/127/16/1723

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial
Office. Once the online version of the published article for which permission is being requested is located,
click Request Permissions in the middle column of the Web page under Services. Further information about
this process is available in the Permissions and Rights Question and Answer document.

Reprints: Information about reprints can be found online at:

http://www.lww.com/reprints

Subscriptions: Information about subscribing to Circulation is online at:

http://circ.ahajournals.org//subscriptions/