To Help an Achy Heart:Management of Pericarditis

Alicia RidgewellPharmacy Resident

2011/12

Outline

Patient Case Drug related problems Goals of therapy Pathphysiology of pericarditis Treatment options Evidence for therapy Recommendations Follow-up

Objectives

Learn basic pathophysiology of acute pericarditis

Be able to list the different causes of pericarditis

Become familiar with treatment options for idiopathic/viral pericarditis

Be aware of the evidence behind use of colchicine

Our Patient: DMID DM, 45 year old male; 65 kg

Admitted Sept. 24th

CC 2-3 day hx of fever and increasing chest pain (feels like knife through rib cage, radiating to shoulders), interferes with work; 10/10 without medication

HPI July 2011, was admitted for chest pain; small pericardial effusion Dx: pericarditis, D/C on ibuprofen

DX CXR on admission small pericardial effusion and pleural effusion: Recurrent pericarditisCXR also shows atelectasis of left lower lobe: ?pneumonia

PMHx IBS – constipation predominate

Patient Case

Fam Hx

Not remarkable

SHx No alcohol or RDUSmokes 1-2 cigarettes/day (no interest in quitting)

Vaccine Hx

Allergies

No flu or pneumococcal vaccinations

Penicillin – anaphylaxis (30 yrs ago)

MPTA -Ibuprofen 400mg (4 tablets at a time – half a bottle in a day)-Oral sodium phosphate once per month

Review of Systems: Sept. 27thVitals Temp:356, HR: 74(reg), BP: 101/62, RR: 16, O2 sat

95 (RA)

CNS Not remarkable

HEENT Not remarkable

RESP Not remarkable; pain in chest when breaths deeply

CVS Chest pain when lying down (better if sitting up)

GI/GU Gas/bloating - constipated

MSK/DERM

Not remarkable

LABS WBC 9.9, Hgb 109, SrCr 63 (stable) – nothing else remarkable

Patient Case

Medical Condition Medications in hospital

?LL pneumonia Azithromycin 500mg IV daily (day 4)Cefuroxime 750mg IV q8hr (day 4)

Pericarditis Indomethacin 50mg po BID

Stomach protection Pantoprazole 40 mg po dailySucralfate 1g po QID

Pain Hydromorphone 5mg po/IV/SubQ q 3hr prn

Constipation/abdominal discomfort

Bowel protocol prnFleet enema daily prnBuscopan 10mg IV daily prn

Drug Related Problems DM is experiencing continued pericarditis

pain secondary to suboptimal therapy DM is experiencing unresolved

constipation secondary to not receiving regular treatment

DM is at risk of continued constipation secondary to narcotic analgesia

DM is at risk of experiencing adverse effects secondary to receiving unnecessary therapy (sucralfate, buscopan)

Goals of Therapy

Prevent mortality Prevent complications (i.e. cardiac

tamponade) Relieve/reduce pain Resolve pericarditis Prevent recurrance Minimize adverse effects from

medications

Pericarditis Pathophysiology

Viral Pericarditis

Coxsackievirus A & B, influenza virus, mumps, herpes simplex, CMV, epstein-barr

Previous viral infection (i.e. respiratory tract infection)

Can occur in all ages but usually young adults

Simultaneous development of fever and precordial pain 10 – 12 days after a viral illness

Acute Pericarditis Symptoms

Chest pain: acute, severe, retrosternal, precordial; refers to neck and shoulders– Pleuritic: sharp; aggravated by inspiration,

coughing, changes in body position Audible friction rub Modest increase in trops and CK Diffuse ST-segment elevations Pericardial effusion

Treatment options

Target underlying cause if possible For viral or idiopathic pericarditis:

– NSAIDs (ibuprofen, aspirin, indomethacin, ketorolac)

– Colchicine– Glucocorticoids (i.e. prednisone)

PICO

In a 45 year old male with recurrent pericarditis, what is the evidence for use of colchicine in combination with NSAID therapy?

Literature Search

Up-to-date: reference list Pubmed. Search terms used:

– Pericarditis– Colchicine– NSAIDs

Results: 2 RCT, open label – CORE and COPE

Evidence: CORE3

Design

Prospective, open label randomized trial

P Aults (≥18yrs), 1st episode of recurrent pericarditis, previous viral or idiopathic pericarditis, no contraindication to colchicine

I/C Group 1: Aspirin 800mg po q 6-8 hrs x 7-10 days (3-4 week taper)

Group 2: Aspirin at same dose + colchicine 1-2mg day 1 then 0.5-1mg daily x 6 months

O Primary: recurrence rate; secondary: symptoms persistence 72 hours after treatment onset

Evidence: CORE resultsRecurrence Rates % (at 18 months)

Symptom Persistence beyond 72 hr (%)

Adverse Drug Reactions

Serious adverse events

Group 1: 50.6

Group 2: 24

P = 0.02

ARR = 26.6%

Group 1: 31

Group 2: 10

P= 0.03

Group 1: 6 pts

Group 2: 3 pts(all 3 pts reported diarrhea – d/c therapy)

None reported

• Limitations: patients unable to take aspirin allowed to use prednisone; open label

Evidence: COPE4

Design

Prospective, open label randomized trial

P Aults (≥18yrs), 1st episode of acute pericarditis (due to viral, idiopathic, autoimmune causes), no contraindication to colchicine

I/C Group 1: Aspirin 800mg po q 6-8 hrs x 7-10 days (3-4 week taper)

Group 2: Aspirin at same dose + colchicine 1-2mg day 1 then 0.5-1mg daily x 3 months

O Primary: recurrence rate; secondary: symptoms persistence 72 hours after treatment onset

Evidence: COPE resultsRecurrence Rates % (at 18 months)

Symptom Persistence beyond 72 hr (%)

Adverse Drug Reactions

Serious adverse events

Aspirin: 23.5

Aspirin + colchicine: 8.8

Pred: 86.7

Pred + colchicine: 11.1

P < 0.001

Group 1: 36.7

Group 2: 11.7

P= 0.003

Group 1: 4 pts(abd pain, dyspepsia)

Group 2: 5 pts(all 5 pts reported diarrhea – d/c therapy)

None reported

• Limitations: did not report subgroups for secondary or outcome; open label

Alternatives

1) Increase indomethacin 50 mg po TID2) Addition of colchicine 0.6mg po BID3) Addition of prednisone 0.5 – 1

mg/kg/day4) D/C indomethacin; give aspirin 650mg

po q6 hr daily + colchicine 0.6 po BID5) D/C indomethacin; give aspirin6) D/C indomethacin; give prednisone +

aspirin

Recommendations

Addition of colchicine 0.6mg po BID– No improvement in 72hr d/c

indomethacin, start aspirin D/C hydromorphone

Other suggestions:– Abx step-down– D/C buscopan, fleet enema, sucralfate– Lactulose 30 mL po daily x 2 days– Docusate sodium 200mg po daily

Monitoring PlanParameter Degree of

ChangeFrequency Who will

monitor

Vitals: Temp, HR, BP, RR

Increase Daily Pharm/MD

Chest pain (PQRST)

Worsening/resolution

Daily Nurse/pharm/MD

Pleural Effusion

Worsening Daily - Weekly MD

Cardiac Tamponade

Occurrence Daily - Weekly MD

Side effects (N/V/D; abdominal pain, cramping)

Presence Daily Nurse/pharm

Constipation Resolution BID x 2 daysThen daily

Nurse/pharm

WBC, Hgb, SrCr, K+

Outside normal limits

q2days Pharm/MD

Patient Update

Sept. 27th therapy adjusted (colchicine added)

Sept. 28th Patient left AMA – Did not take discharge prescription (no

therapy continued)

Questions?

References

1). MD consult. Elsevier 2011. Available from URL: www.mdconsult.com. Accessed: Oct. 2, 2011.

2). Imazio M, LeWinter MM, Downey BC. Treatment of acute pericarditis. Up-to-Date 2011. www.uptodate.com. Accessed Sept. 27, 2011

3). Imazio M, Bobbio M et al. Colchicine as First-Choice Therapy for Recurrent Pericarditis: Results of the CORE trial. Arch Intern Med.2005;165:1987-91

4). Imazio M, Bobbio M et al. Colchicine in Addition to Conventional Therapy for Acute Pericarditis: Results of the COPE trial. Circulation.2005;112:2012-16

5). Maisch B, Seferovic PM et al. Guidelines on the Diagnosis and Management of pericardial diseases. European Heart Journal.2004;25:587-610

6). Fauci AS et al. Harrison’s Principles of Internal Medicine. 17th ed. McGraw Hill Medical. New York. 2008.p.1489-94

7). Lange RA, Hillis LD. Acute Pericarditis. N Engl J Med.2004;351:2195-2028). Imazio M, Brucato A et al. Medical therapy of pericardial diseases Part 1:

Idiopathic and infectious pericarditis. J Cardiovasc Med. 2010;11:712-22