10/24/2019 Management of Idiopathic Pericarditis: Old Drugs with New Tricks Nic Nicholas C olas C. S Schwier ier, Ph Pharm.D., B arm.D., BCPS - PS - AQ C Cardiology iology Assistant Professor Director, PGY-2 Cardiology Pharmacy Residency Program College of Pharmacy University of Oklahoma Health Sciences Center Walter P. Scheffe 2019 CPE Series Financial Disclosure and Resolution Under guidelines established by the Accreditation Council for Pharmacy Education (ACPE), disclosure must be made regarding financial relationships with commercial interests within the last 12 months. ▪ I have no no relevant financial relationships or affiliations with commercial interests to disclose. ▪ I will I will be be discussing experimental or off-label drugs, therapies and/or devices that have not been approved by the FDA. ▪ None of the medications that I will be discussing today have FDA-approved indications for the treatment of pericarditis. ▪ I will make clinical recommendations during this presentation. 1
10/24/2019 Learning Objectives At the completion of this activity, pharmacists will be able to: 1. Select appropriate anti-inflammatory therapy based on patient-specific factors. 2. Outline a tapering schedule for anti-inflammatory therapies. 3. Identify drug interactions associated with colchicine. 4. List monitoring parameters for colchicine, anti-inflammatory therapy, and corticosteroids. 5. Describe an empiric pharmacotherapy plan for a patient with acute or recurrent idiopathic pericarditis. Pre-Assessment Question 1 ▪ Which of the following medications increases the risk of recurrence in acute idiopathic (viral) pericarditis? A. Aspirin B. Colchicine C. Prednisone D. Anakinra 2
10/24/2019 Pre-Assessment Question 2 ▪ Which of the following is an appropriate anti-inflammatory regimen for an adult patient diagnosed with acute idiopathic (viral) pericarditis? A. Aspirin 325 mg PO daily for 1 month, then taper B. Ibuprofen 800 mg PO TID for 6 months C. Indomethacin 50 mg PO TID for 1 week, then taper D. Ketorolac 15 mg PO daily for 3 weeks, then taper Pre-Assessment Question 3 ▪ Which of the following medications increases the plasma concentration of colchicine? A. Carvedilol B. Rifampin C. Pravastatin D. Levothyroxine 3
10/24/2019 Pre-Assessment Question 4 ▪ Which of the following parameters would be appropriate for monitoring the safety of colchicine? A. Creatine phosphokinase B. Blood glucose C. INR D. Fasting lipid panel What is Pericarditis? ▪ Pericarditis – inflammation of the pericardium ▪ Most common form of pericardial disease ▪ Can “look” like other serious cardiovascular disorders ▪ Acute myocardial infarction ▪ Aortic dissection ▪ Pulmonary embolism ▪ Myocarditis 4
10/24/2019 Importance of the Pericardium ▪ Pericardium functions to ▪ lubricate the heart ▪ anchor heart to mediastinum ▪ prevent overfilling of heart ▪ protect heart from infection ▪ Pericardium is comprised of two layers ▪ Contains upwards of 50 mL of pericardial fluid to help lubricate the two layers of the pericardium Prog Cardiovasc Dis. 2017;59:341-348. Pathophysiology of Pericarditis ▪ Inflammatory disease involving the pericardium ▪ Visceral and parietal layers can rub together to produce inflammation and potentially pain ▪ Thought to be caused by autoinflammatory or autoimmune mechanisms ▪ Interleukin-1 ▪ Type 1 interferon Eur Heart J 2015; 36: 2921-2964. Curr Cardiol Rep. 2017;19:60. 5
10/24/2019 Epidemiology of Pericarditis ▪ Incidence rate of hospitalization for acute pericarditis occurs in 3.32 per 100,000 person-years. ▪ Majority of patients with pericarditis present within the fifth decade of life. ▪ Care related to pericarditis is associated with high cost and healthcare burden, with a length of stay of approximately 4 days N Engl J Med . 2013;369:1522-1528. Lancet. 2014;383:2232-2237. Cardiology. 2016; 135: 27-35. Ann Intern Med. 2011;155:409-414. Circulation. 2014; 130: 1601-1606. Circulation. 2005;112:2012-2016. Arch Intern Med. 2005;165:1987-1991. Outcomes Associated with Pericarditis ▪ Incessance ▪ Procedural care ▪ Pericardiectomy ▪ Recurrence ▪ Pericardial window ▪ Pericardiotomy ▪ Impaired quality of life ▪ Constrictive pericarditis ▪ Adverse effects secondary to prolonged use of corticosteroids ▪ Cardiac tamponade Eur Heart J 2015; 36: 2921-2964. 6
10/24/2019 Relevance of Pericarditis to Pharmacy Practice ▪ Pharmacotherapy is a mainstay of treatment for certain etiologies of pericarditis. ▪ Pharmacotherapy used to treat such etiologies are associated with potentially significant adverse effects and requires diligent monitoring. ▪ Pericarditis is associated with significant morbidity related to certain medications. ▪ Pharmacists in ever ery practic y practice area area can potentially influence patient-related outcomes associated with pericarditis. J Pharm Pract. 2019;1-8. Diagnosis of Pericarditis ▪ Pericarditic chest pain ▪ Elevated inflammatory markers ▪ C-reactive protein (CRP) ▪ Electrocardiogram (ECG) changes ▪ High sensitivity (hs)-CRP ▪ White blood cell (WBC) count ▪ New or worsening pericardial ▪ Erythrocyte sedimentation rate (ESR) effusion ▪ Evidence of pericardial ▪ Pericardial friction rub inflammation by an imaging technique Eur Heart J 2015; 36: 2921-2964 7
10/24/2019 Important Definitions Related to Pericarditis ▪ Subacut Subacute ▪ Acut Acute p e pericard ricarditis itis ▪ Recurrent current pericardit pericarditis is ▪ Incessan Incessant pericarditis pericarditis ▪ Chronic pericarditis ▪ Constrictive pericarditis Eur Heart J 2015; 36: 2921-2964. Etiologies of Pericarditis ▪ Idiopath Idiopathic ic ▪ Metabolic ▪ Infectious ▪ Amyloidosis ▪ Viral Viral ▪ Pulmonary arterial hypertension ▪ Bacterial ▪ Fungal ▪ Aortic dissection ▪ Au Autoimmune mmune ▪ Chronic heart failure ▪ Traumatic/Iatr aumatic/Iatrogenic ogenic ▪ Medication Medications… s… ▪ Ne Neoplastic lastic Eur Heart J 2015; 36: 2921-2964. 8
10/24/2019 Drug-Induced Pericarditis ▪ Lupus-like syndrome ▪ Minoxidil ▪ Procainamide ▪ Anthracyclines ▪ Hydralazine ▪ Methyldopa ▪ Clozapine ▪ Isoniazid ▪ Anti-TNF α agents ▪ Phenytoin Eur Heart J 2015; 36: 2921-2964. Idiopathic (Viral) Pericarditis ▪ Most common type of pericarditis in the Western hemisphere ▪ Associated with inflammatory sequelae ▪ The majority of patients studied in landmark pharmacotherapy studies include idiopathic or or viral etiologies of pericarditis ▪ Recurrence is the most common complication associated with idiopathic or or viral etiologies pericarditis Eur Heart J 2015; 36: 2921-2964. 9
10/24/2019 Timeline of Literature/Guideline Updates ESC ESC COPE CORE CORP ICAP CORP-2 AIRTRIP ESC ESC Guideline Guid RHAPSODY Guidelines Guid trial trial trial trial trial trial UPD UPDATE trial 2004 004 2005 2005 2011 2013 2014 2016 20 2015 Negative Prognostic Factors Associated with Idiopathic (Viral) Pericarditis Major Minor ▪ Fever >38°C ▪ Myopericarditis ▪ Subacute onset ▪ Immunosupp Immunosuppression ression ▪ Large pericardial effusion ▪ Trauma ▪ Cardiac tamponade ▪ Oral anticoagulant Oral anticoagulant therap therapy ▪ Lac Lack of of response t response to aspirin (ASA) aspirin (ASA) or non steroidal or non st eroidal anti- anti- inflammatory drugs (NS inf drugs (NSAIDs) s) after at af r at least 1 least 1 week of eek of therap therapy Circulation 2007; 115: 2739-2744. Eur Heart J 2015; 36: 2921-2964. 10
10/24/2019 Check-Point: QUESTIONS? Management of Pericarditis 11
10/24/2019 2015 ESC Guideline Recommendations for the Treatment of Acute Pericarditis Reco commendat mmendatio ion Class ass Level vel ASA or NSAIDs are recommended as first-line therapy for acute pericarditis with I A gastroprotection. Colchicine is recommended as first-line therapy for acute pericarditis as an adjunct to I A ASA/NSAID therapy. Serum CRP should be considered to guide the treatment length and assess the response to IIa C therapy. Low-dose corticosteroids should be considered for acute pericarditis in cases of IIa C contraindication/failure of aspirin/NSAIDs and colchicine, and when an infectious cause has been excluded. Corticosteroids are not recommended as first-line therapy for acute pericarditis. III C Eur Heart J 2015; 36: 2921-2964. 2015 ESC Guideline Recommendations for the Treatment of Recurrent Pericarditis Reco commendat mmendatio ion Class ass Level vel ASA and NSAIDs are mainstays of treatment and are recommended at full doses, if tolerated, I A until complete symptom resolution. Colchicine (0.5 mg twice daily or 0.5 mg daily for patients < 70 kg or intolerant to higher I A doses); use for 6 months is recommended as an adjunct to aspirin/NSAIDs. CRP dosage should be considered to guide the treatment duration and assess the response to IIa C therapy. After CRP normalization, a gradual tapering of therapies should be IIa C considered, tailored to symptoms and CRP, stopping a single class of drugs at a time. Drugs such as intravenous (IV) immunoglobulin (IG), anakinra and azathioprine may be IIb C considered in cases of corticosteroid-dependent recurrent pericarditis in patients not responsive to colchicine. Eur Heart J 2015; 36: 2921-2964. 12
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