ABSTRACT: Acute pericarditis is the most common form of
pericardial disease that results in the need for empirical
anti-inflammatory treatment. Aspirin and other nonsteroidal
anti-inflammatory drugs, prednisone, and colchicine are the mainstays of
therapy. These agents are used for symptom control and to reduce the
risk of further complications, including recurrent pericarditis,
constrictive disease, and cardiac tamponade. Strong evidence has emerged
for the use of colchicine to treat and prevent recurrent pericarditis.
Therapies for acute pericarditis carry their own risks of adverse
effects. Therefore, pharmacists play a vital role in educating patients,
improving their care, and promoting the safe and effective use of these
US Pharm. 2014;39(4):52-57.
Acute pericarditis (inflammation of the pericardial sac) is the most
common pericardial disease, accounting for 5% of emergency department
admissions in patients presenting with nonischemic chest pain.1,2
In the United States, most cases of acute pericarditis in
immunocompetent hosts are predominantly of idiopathic or viral origin.1,3
Other causes include radiation; malignancies; trauma; infectious
diseases (e.g., mycoplasmal, fungal, bacterial); drugs (e.g.,
procainamide, isoniazid, hydralazine); autoimmune disorders (e.g.,
lupus, rheumatoid arthritis, vasculitis, scleroderma, sarcoidosis,
inflammatory bowel disease); metabolic disorders (hypothyroidism,
uremia, ovarian hyperstimulation syndrome); and cardiac disorders (early
infarction, postcardiac injury, myocarditis, dissecting aortic
High-risk patients should be hospitalized, as they have a specific
etiology and are more likely to experience short-term complications.4,5
Indicators of poor prognosis include fever, leukocytosis, suspected
cardiac tamponade, large pericardial effusion, immunocompromised state,
history of warfarin treatment, acute trauma, refractoriness to a 7-day
course of nonsteroidal anti-inflammatory drugs (NSAIDs), and elevated
cardiac troponin.4,5 Complications such as cardiac tamponade
and constrictive pericarditis occur more frequently in patients with an
identified etiology and rarely in those with idiopathic or viral causes.2,6
Recurrent pericarditis occurs in 10% to 30% of pericarditis patients, usually weeks to months later.2,7
Recurrent pericarditis develops at least 6 weeks after medications for
the initial or previous attack are discontinued, whereas incessant
pericarditis occurs within the 6-week period immediately following
discontinuation. Recurrent pericarditis is most commonly idiopathic,
viral, or autoimmune in origin.8 Risk factors for recurrence
are not well defined; however, a favorable response to initial treatment
of the index case of pericarditis with aspirin or other NSAIDs is
associated with lower risk, whereas initial glucocorticoid use is
associated with a higher risk.9-11 Fortunately, most patients with recurrence experience only one to two more attacks, and severe complications are rare.10-12
Acute pericarditis presents in a variety of ways, depending upon the
underlying etiology. Pericarditis with an infectious etiology may be
preceded by signs and symptoms of infection; by flulike symptoms, for a
viral etiology; or, for an autoimmune or malignancy etiology, by
exacerbation of symptoms of the underlying disorder. The major clinical
signs and symptoms include ECG changes with recent widespread ST
elevation or PR depression, pericardial friction rub, sharp or stabbing
chest pain, fatigue, breathlessness, and palpitations.13
Patients with pericarditis often present with pericardial effusion. Such
patients should be closely monitored for signs of cardiac tamponade, a
potentially lethal complication of pericarditis.
During the course of pericarditis, approximately 85% of patients have
an audible friction rub upon physical examination. This is a
high-pitched scratchy or squeaky sound best heard at end expiration with
the patient leaning forward.3 Chest pain associated with
acute pericarditis is usually sudden in onset, retrosternal, and
pleuritic in that it is exacerbated by inspiration. The pain may lessen
when the patient leans forward or assumes the upright position.
Classically, the 12-lead ECG in patients with acute pericarditis
shows widespread upward concave ST-segment elevation and PR-segment
depression. There are four levels of ECG abnormalities: stage I, diffuse
ST-segment elevation and PR-segment depression; stage II, normalization
of the ST and PR segments; stage III, widespread T-wave inversions; and
stage IV, normalization of T waves.3
Echocardiograms frequently are normal in patients with the clinical
syndrome of acute pericarditis, unless there is an associated
pericardial effusion. The finding of pericardial effusion supports
diagnosis, but its absence does not exclude acute pericarditis. Chest
radiographs are usually normal in patients with acute pericarditis,
unless there is a large effusion with an accumulation of >200 mL of
Markers of inflammation, such as WBC count, erythrocyte sedimentation
rate, and C-reactive protein concentration, are usually elevated. These
findings are nonspecific to pericarditis. Serum cardiac troponin I
levels also have been shown to be elevated in some patients.3
The treatment of acute pericarditis should be guided by the
underlying cause. Ninety percent of acute pericarditis cases are
idiopathic or viral, making NSAIDs, prednisone, and colchicine the
foundations of therapy.3,14-16 Drug therapy is empirical and targets symptom control.
NSAID therapy is initiated empirically for idiopathic pericarditis and generally leads to symptom resolution within 2 weeks.4
NSAIDs other than aspirin should be avoided in patients who develop
postinfarction pericarditis (Dressler syndrome), owing to these agents’
inhibitory effects on scar-tissue formation and the increased risk of
infarction-zone thinning.17-20 In the case of Dressler
syndrome, high-dose (HD) aspirin is preferred. Indomethacin should be
avoided in elderly patients and in patients with coronary artery
disease, owing to its negative impact on coronary flow; ibuprofen is the
preferred NSAID.21 Subsequent tapering of these agents should be considered to reduce the risk of recurrence.14
Corticosteroid therapy has resulted in rapid symptom control;
however, it has been linked to higher rates of recurrent pericarditis.11,14,22,23
The use of corticosteroids is also limited by some other systemic
adverse effects (AEs) associated with long-term corticosteroid therapy,
thereby rendering intrapericardial instillation of a nonabsorbable
steroid a viable therapeutic option.24 Corticosteroids are
reserved for patients who have failed NSAIDs. In Dressler syndrome,
corticosteroids should be reserved only for refractory symptoms, because
these agents can delay myocardial healing.14 Treatment can
last up to 4 weeks, so tapering is recommended. To prevent recurrence,
NSAIDs and/or colchicine should be added toward the end of the taper.25
Colchicine is an anti-inflammatory agent that works by inhibiting
tubulin polymerization, thereby interfering with migration and
phagocytosis and reducing the inflammatory cycle. For acute
pericarditis, colchicine is generally used in combination with other
therapies. This agent may be useful in recurrent pericarditis, which is
immune-mediated, owing to its ability to disrupt the inflammatory cycle
involved in pathogenesis.26 Treatment typically lasts up to
12 weeks, but may be administered up to 1 year in the case of recurrent
pericarditis. Recent studies have provided strong evidence of
colchicine’s effectiveness in treating pericarditis. TABLE 1 summarizes treatment alternatives and dosing for acute pericarditis.2,3,20
Earlier Studies: The COlchicine for acute
PEricarditis (COPE) and COlchicine for REcurrent pericarditis (CORE)
trials were the first prospective, open-label, randomized studies to
support the use of colchicine for acute and recurrent pericarditis.9,10
COPE and CORE investigated colchicine (>70 kg: 1-2 mg day 1, then
0.5-1 mg daily × 3 months; ≤70 kg: 1 mg day 1, then 0.5 mg daily × 3
months) in combination with HD aspirin (800 mg q6-8h × 7 days and
gradual taper over 3-4 weeks) versus HD aspirin alone.9 In cases in which aspirin was contraindicated, prednisone (1-1.5 mg/kg daily × 1 month, followed by taper) was used.9
COPE was conducted in 120 adult patients diagnosed with acute pericarditis.9 The primary endpoint was recurrence rates of incessant-type and intermittent-type disease.9
At 18 months, colchicine significantly reduced recurrence rates by more
than 20% compared with aspirin alone (10.7% vs. 32.4%, respectively; P = .004), with a number needed to treat (NNT) of 5.9 CORE examined 84 adult patients with a diagnosis of first recurrence of pericarditis.10 The primary endpoint was colchicine’s effectiveness as first-line therapy for recurrent pericarditis.10
At 18 months, colchicine significantly reduced the recurrence rate by
more than 25% compared with aspirin (24% vs. 50.6%, respectively; P = .02), with an NNT of 4.10
Both COPE and CORE revealed that previous corticosteroid use was
associated with a more than twofold increase in further recurrences.9,10 The major AE reported in these trials was diarrhea, possibly because of the use of higher doses of colchicine.9,10
COPE and CORE set the stage for the use of colchicine in treating acute
and recurrent pericarditis; however, the open-label design of these
studies was a major limitation, so definitive conclusions could not be
Recent Studies: Colchicine for Recurrent
Pericarditis (CORP) was the first prospective, multicenter,
double-blind, randomized, placebo-controlled trial investigating the use
of colchicine in treating this type of pericarditis.27
CORP’s main objective was to evaluate the efficacy and safety of
colchicine for secondary prevention of recurrent pericarditis in 120
patients with a first recurrence of pericarditis.27 In
addition to conventional therapy (aspirin 800-1,000 mg or ibuprofen 600
mg q8h × 7 days with gradual taper over 3-4 weeks), patients were
randomly assigned to colchicine (>70 kg: 1-2 mg on day 1, then 0.5-1
mg daily × 6 months; ≤70 kg: 0.5 mg q12h day 1, then 0.5 mg daily × 6
months) or placebo.27 When conventional therapy was contraindicated, prednisone (0.2-0.5 mg/kg daily × 1 month, followed by taper) was used.27
At 18 months, colchicine significantly reduced recurrence rates by
>30% compared with placebo (24% vs. 55% recurrence, respectively; P <.0001), with an NNT of 3.27 The most common AE was diarrhea.27
The Investigation on Colchicine for Acute Pericarditis (ICAP) was a
multicenter, double-blind, randomized trial of 240 adult patients with
acute pericarditis.28 The primary objective was to evaluate
the efficacy and safety of colchicine in treating a first attack of
acute pericarditis and preventing recurrences.28 In addition
to conventional therapy (aspirin 800 mg or ibuprofen 600 mg q8h × 7-10
days followed by taper over 3-4 weeks), patients were randomly assigned
to colchicine (>70 kg: 0.5-1 mg daily × 3 months; ≤70 kg: 0.5 mg
daily × 3 months) or placebo.28 When conventional therapy was contraindicated, prednisone (0.2-0.5 mg/kg daily × 2 weeks, followed by taper) was used.28
At 18 months, colchicine significantly reduced the recurrence rate by
about 20% compared with conventional therapy alone (16.7% vs. 37.5%,
respectively; P <.001), with an NNT of 5.28 Diarrhea was the AE most commonly reported.28
CORP led to the recommendation of colchicine as a first-line agent
for the treatment of recurrent pericarditis in the 2004 guidelines of
the European Society of Cardiology.14 ICAP also provided
conclusive evidence that colchicine was effective for first acute
attacks. Both CORP and ICAP had some limitations, including small sample
size, which may have limited the detection of rare AEs. Because
patients with neoplastic or bacterial pericarditis were excluded from
these studies, the results do not apply to these subsets. The optimal
duration of colchicine therapy has not been identified, so further
clarification is warranted.
Role of the Pharmacist
Pharmacists play a key role within the healthcare system in informing
patients, improving their care, and promoting the safe and effective
use of medications. Pharmacists can ensure the safe use of agents used
to treat acute pericarditis by educating patients about their
medications, recommending appropriate therapies and dose adjustments
based on renal function and comorbidities, screening for drug-drug and
drug-food interactions, and monitoring for AEs. For instance, in
patients receiving NSAIDs, pharmacists can take the lead in evaluating
patients and considering the addition of misoprostol or proton pump
inhibitors for prophylaxis against NSAID-related gastrointestinal
complications such as ulcers, especially in high-risk patients.29
In patients in whom glucocorticoid therapy is warranted, pharmacists
can recommend appropriate tapering doses and educate patients and
providers about possible long-term AEs associated with prolonged use of
corticosteroids. In addition, pharmacists should evaluate the need for
prevention of glucocorticoid-induced osteoporosis and recommend calcium,
vitamin D, and bisphosphonates as indicated.30
In terms of colchicine, it is imperative that appropriate dosages be
used in underweight patients and that frequent monitoring of possible
colchicine AEs be conducted. Owing to colchicine’s safety profile, even
at lower dosages, caution should be exercised in patients with renal or
hepatic impairment. Finally, pharmacists should ensure that medication
guides are distributed when required (i.e., with NSAIDs and colchicine).
NSAIDs, glucocorticoids, and colchicine have been demonstrated to
have clinical benefit in the treatment of pericarditis. Recent studies
have provided strong evidence suggesting that colchicine is an effective
treatment option for both acute and recurrent pericarditis. Pharmacists
can play a vital role in ensuring the safe and effective treatment of
acute and recurrent pericarditis.
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