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Clinician Update

Treatment of Acute and Recurrent Idiopathic Pericarditis


Leonard S. Lilly, MD

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

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 DOI: 10.1161/CIRCULATIONAHA.111.066365

1723
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
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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
Lilly   Acute and Recurrent Idiopathic Pericarditis  1725

or placebo, in addition to aspirin or


Clinical Presentation of Acute Pericarditis another NSAID.17 The rate of subse-
• Pleuritic, positional chest pain quent recurrence was 24% in those
• Pericardial rub randomized to colchicine compared
• ECG abnormalities with 55% in the placebo group. In
• ± Pericardial effusion on imaging 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.
High-risk Glucocorticoids
Features Symptoms of pericarditis recurrence
respond promptly to glucocorticoid
• Fever > 38°C
therapy.1 However, when administered
• Subacute onset
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in this situation, slow tapering and a


• Anticoagulated prolonged course may be required to
• Immunocompromised Yes prevent recrudescent symptoms, with
• Hypotension the potential for long-term steroid-
• Jugular venous associated side effects. Furthermore,
distension the risk of additional recurrences of
• Large effusion pericarditis is augmented by steroid
Admit to
use.12,14,16 Therefore, the consensus is
Hospital
to initially treat recurrent episodes of
pericarditis with an NSAID plus col-
chicine and to prescribe glucocorti-
No coids only for refractory cases.
Patients sometimes present with
chest discomfort reminiscent of prior
pericarditis, which is interpreted as
Outpatient Management
a recurrence, even in the absence of
• NSAID x 2 weeks objective findings (no pericardial rub,
• ± Colchicine x 3 months ECG or echocardiographic abnormali-
ties, or elevation of serum inflamma-
Figure.  Initial triage pathway in acute pericarditis. NSAID indicates nonsteroidal anti- tory markers). Although a trial of an
inflammatory drug. NSAID plus colchicine may be reason-
able in this situation, glucocorticoids
repeat over extended periods of time and episode, a gradual tapering of the drug
should certainly be avoided.18
may lead to substantial disability. A first over 2 to 4 weeks after symptoms
Imazio and colleagues15 compared
recurrence typically presents within 18 improve is recommended.16
2 steroid dosage intensities in recur-
months, and findings are similar to the
Colchicine rent pericarditis: Prednisone 0.2 to 0.5
initial episode, including pleuritic chest
Use of colchicine in the COPE trial mg·kg−1·d−1 versus the higher com-
pain, diffuse ST-segment elevations,
was associated with fewer initial peri- monly used dose of 1.0 mg·kg−1·d−1
a pericardial friction rub, and elevated
carditis recurrences.12 Additionally, the for 4 weeks, followed by a slow taper.
serum markers of inflammation.16
Colchicine for Recurrent Pericarditis The lower-dose regimen was effec-
(CORE) trial randomized 84 patients tive, whereas the higher dosage was
Pharmacological Treatment who had already had a first recurrence associated with more side effects and a
Nonsteroidal Anti-inflammatory to aspirin or aspirin plus colchicine.16 greater number of subsequent pericar-
Drugs Compared with aspirin alone, the com- ditis recurrences and hospitalizations.
In the absence of prospective trial bination reduced the rate of additional Thus, a now common approach to the
evidence, aspirin or another NSAID recurrences by 50%. use of steroids in patients with recurrent
should form the foundation of therapy Most recently, the double-blinded pericarditis whose symptoms are refrac-
for recurrences (Table).4 However, in Colchicine for Recurrent Pericarditis tory to an NSAID plus colchicine is the
contrast to the brief course of NSAID (CORP) trial randomized 120 patients lower-dose prednisone regimen listed in
generally prescribed for an initial with a first recurrence to colchicine the Table. With prolonged corticosteroid
1726  Circulation  April 23, 2013

use, osteoporosis prevention (eg, cal- parenteral NSAID ketorolac may be PR, Torp-Pedersen C, Gislason GH. Long-
term cardiovascular risk of nonsteroidal
cium, vitamin D, and bisphosphonates) beneficial. For recurrent episodes of
anti-inflammatory drug use according to time
should be considered. pericarditis, treatment with an NSAID passed after first-time myocardial infarc-
A common cause of referral to plus colchicine is recommended, but tion: a nationwide cohort study. Circulation.
specialized pericardial centers is the for a more prolonged course. During 2012;126:1955–1963.
11. Adler Y, Finkelstein Y, Guindo J, Rodriguez
inability to taper glucocorticoid ther- NSAID treatment, concurrent gastric de la Serna A, Shoenfeld Y, Bayes-Genis A,
apy below a certain dosage (typically protection therapy should be consid- Sagie A, Bayes de Luna A, Spodick DH.
≈15 mg of prednisone daily) without ered. Only for truly refractory cases Colchicine treatment for recurrent pericar-
ditis: a decade of experience. Circulation.
reemergence of symptoms, despite should glucocorticoid therapy be used. 1998;97:2183–2185.
concurrent NSAID plus colchicine 12. Imazio M, Bobbio M, Cecchi E, Demarie D,
treatment. An often effective strategy Disclosures Demichelis B, Pomari F, Moratti M, Gaschino
in this circumstance is to resume the G, Giammaria M, Ghisio A, Belli R, Trinche-
None.
ro R. Colchicine in addition to conventional
lowest prior steroid dosage that had therapy for acute pericarditis: results of the
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10. Olsen AM, Fosbøl EL, Lindhardsen J, Folke
cially to reduce the rate of recurrence. F, Charlot M, Selmer C, Bjerring Olesen J, Key Words: colchicine ◼ drug therapy
For initially refractory symptoms, the Lamberts M, Ruwald MH, Køber L, Hansen ◼ pericarditis
Treatment of Acute and Recurrent Idiopathic Pericarditis
Leonard S. Lilly

Circulation. 2013;127:1723-1726
doi: 10.1161/CIRCULATIONAHA.111.066365
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