1. To Help an Achy Heart: Management of Pericarditis Alicia Ridgewell Pharmacy Resident 2011/12

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

3. 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

4. Our Patient: DM IDDM, 45 year old male; 65 kg Admitted Sept. 24th CC2-3 day hx of fever and increasing chest pain (feels like knife through rib cage, radiating to shoulders), interferes with work; 10/10 without medication HPIJuly 2011, was admitted for chest pain; small pericardial effusion Dx: pericarditis, D/C on ibuprofen DXCXR on admission  small pericardial effusion and pleural effusion: Recurrent pericarditis CXR also shows atelectasis of left lower lobe: ?pneumonia PMHxIBS – constipation predominate

5. Patient Case Fam HxNot remarkable SHxNo alcohol or RDU Smokes 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

6. Review of Systems: Sept. 27th VitalsTemp:35 6, HR: 74(reg), BP: 101/62, RR: 16, O 2 sat 95 (RA) CNSNot remarkable HEENTNot remarkable RESPNot remarkable; pain in chest when breaths deeply CVSChest pain when lying down (better if sitting up) GI/GUGas/bloating - constipated MSK/DERMNot remarkable LABSWBC 9.9 , Hgb 109 , SrCr 63 (stable) – nothing else remarkable

7. Patient Case Medical ConditionMedications in hospital ?LL pneumoniaAzithromycin 500mg IV daily (day 4) Cefuroxime 750mg IV q8hr (day 4) PericarditisIndomethacin 50mg po BID Stomach protectionPantoprazole 40 mg po daily Sucralfate 1g po QID PainHydromorphone 5mg po/IV/SubQ q 3hr prn Constipation/abdominal discomfort Bowel protocol prn Fleet enema daily prn Buscopan 10mg IV daily prn

8. 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)

9. Goals of Therapy Prevent mortality Prevent complications (i.e. cardiac tamponade) Relieve/reduce pain Resolve pericarditis Prevent recurrance Minimize adverse effects from medications

10. Pericarditis Pathophysiology

11. 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

12. 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

13. Treatment options Target underlying cause if possible For viral or idiopathic pericarditis: – NSAIDs (ibuprofen, aspirin, indomethacin, ketorolac) – Colchicine – Glucocorticoids (i.e. prednisone)

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

15. Literature Search Up-to-date: reference list Pubmed. Search terms used: – Pericarditis – Colchicine – NSAIDs Results: 2 RCT, open label – CORE and COPE

16. Evidence: CORE 3 DesignProspective, open label randomized trial PAults (≥18yrs), 1 st episode of recurrent pericarditis, previous viral or idiopathic pericarditis, no contraindication to colchicine I/CGroup 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 OPrimary: recurrence rate; secondary: symptoms persistence 72 hours after treatment onset

17. Evidence: CORE results Recurrence 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

18. Evidence: COPE 4 DesignProspective, open label randomized trial PAults (≥18yrs), 1 st episode of acute pericarditis (due to viral, idiopathic, autoimmune causes), no contraindication to colchicine I/CGroup 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 OPrimary: recurrence rate; secondary: symptoms persistence 72 hours after treatment onset

19. Evidence: COPE results Recurrence 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

20. Alternatives 1) Increase indomethacin 50 mg po TID 2) Addition of colchicine 0.6mg po BID 3) Addition of prednisone 0.5 – 1 mg/kg/day 4) D/C indomethacin; give aspirin 650mg po q6 hr daily + colchicine 0.6 po BID 5) D/C indomethacin; give aspirin 6) D/C indomethacin; give prednisone + aspirin

21. 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

22. Monitoring Plan ParameterDegree of Change FrequencyWho will monitor Vitals: Temp, HR, BP, RR IncreaseDailyPharm/MD Chest pain (PQRST) Worsening/resol ution DailyNurse/pharm/M D Pleural EffusionWorseningDaily - WeeklyMD Cardiac Tamponade OccurrenceDaily - WeeklyMD Side effects (N/V/D; abdominal pain, cramping) PresenceDailyNurse/pharm ConstipationResolutionBID x 2 days Then daily Nurse/pharm WBC, Hgb, SrCr, K+ Outside normal limits q2daysPharm/MD

23. Patient Update Sept. 27 th  therapy adjusted (colchicine added) Sept. 28 th  Patient left AMA – Did not take discharge prescription (no therapy continued)

24. Questions?

25. References 1). MD consult. Elsevier 2011. Available from URL: www.mdconsult.com. Accessed: Oct. 2, 2011.www.mdconsult.com 2). Imazio M, LeWinter MM, Downey BC. Treatment of acute pericarditis. Up-to- Date 2011. www.uptodate.com. Accessed Sept. 27, 2011www.uptodate.com 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. 17 th ed. McGraw Hill Medical. New York. 2008.p.1489-94 7). Lange RA, Hillis LD. Acute Pericarditis. N Engl J Med.2004;351:2195-202 8). Imazio M, Brucato A et al. Medical therapy of pericardial diseases Part 1: Idiopathic and infectious pericarditis. J Cardiovasc Med. 2010;11:712-22