Updates in the Management of Cardiovascular Diseases. Anna Nogid, PharmD, BCPS Associate Professor of Pharmacy Practice LIU Pharmacy

Updates in the Management of Cardiovascular Diseases Anna Nogid, PharmD, BCPS Associate Professor of Pharmacy Practice LIU Pharmacy

Objectives Discuss updates in treatment recommendations for patients with cardiovascular disorders Develop a treatment plan for a patient with cardiovascular disorders Provide patient education with regard to disease state and drug therapy for patients with CV disorders

Updates in CV Disease Timeline June 2013 Heart failure October 2013 Secondary prevention of atherosclerotic disease November 2013 High blood pressure High cholesterol ASCVD risk assessment February 2014 JNC 8 March 2014 Atrial fibrillation May 2014 secondary stroke prevention

Managing High Blood Pressure

What s New in JNC 8? No definition for hypertension Increased SBP threshold for drug treatment initiation in patients > 60 years of age Similar treatment goals defined for most hypertensive patients Emphasis on lifestyle modifications Recommended selection among 4 specific mediation classes Specific medication classes recommended for racial, diabetic, and CKD patient groups

Treatment goals General population Age 60 years or older: < 150mmHg/90 mmhg Age < 60 years: < 140mmHg/ 90 mmhg CKD: < 140 mmhg/90 mmhg Diabetes: < 140mmHg/90mmHg

Lifestyle Modifications Modification Weight reduction ~ SBP 5-20 mm Hg/10kg Attain & maintain BMI < 25 kg/m 2 Adopt DASH eating plan Fruits/vegetables Low-fat dairy products Reduce saturated fat & cholesterol Physical activity > 30 min/day most days of the week Dietary sodium restriction < 2.4g/day (< 1.5 g/day) Moderate alcohol consumption < 2 drinks/d (men); < 1 drink/d (women) 8-14 mm Hg 4-9 mm Hg 2-8 mmhg 2-4 mm Hg Go AS, et al. Hypertension 2014;63;878-885

Approach to Treatment: JNC 8 JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427

Approach to Treatment: JNC 8 (cont) JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427

Approach to dosing Initiate with 1 or 2 agents from recommended drug class If goal BP is not reached within 1 month, increase dose or add another agent Continue increasing the dose until goal BP is attained Consider alternative antihypertensive agents if needed Avoid ACEI + ARB whenever possible

Adverse Effects of Commonly Utilized Blood-Pressure Lowering Agents Class DHP CCB Non-DHP CCB Diuretics ACEI ARB Adverse effects Peripheral edema, flushing, reflex tachycardia Constipation (verapamil), bradycardia Electrolyte disturbances, hyperuricemia, hyperglycemia, hyperlipidemia Hyperkalemia, SCr, cough, angioedema, hypotension Hyperkalemia, SCr, angioedema, hypotension

Patient Education Blood pressure monitoring Every 2-4 weeks until controlled, then every 3-6 months Self-monitoring for select patients Importance of adherence Lifestyle modifications

Summary Higher BP goals for most patients Beta blockers are no longer preferred initial agents in the general population Main objective is to attain and maintain goal BP Combine drug therapy with lifestyle modifications

Patient Profile 18 Patient Name: BE Address: 75 Dekalb Ave, Brooklyn, NY 11201 Age: 62 Height: 5 8 Weight: 251 lb Sex: F Phone: (800) 249-4957 Medication Profile Date Rx No. Physician Drug/Strength Qty Sig Refills 5/30 112555 Davis Carvedilol 25mg 60 1 bid 2 5/30 111002 Davis Furosemide 40mg 30 1 daily 2 5/30 111003 Davis Fosinopril 40mg 30 1 daily 1 5/30 111004 Wonder Glipizide XL 10mg 30 1 daily 4 5/30 111005 George Tramadol 50mg 60 1 bid 1 4/27 111001 Davis Carvedilol 12.5mg 60 1 bid 2 4/27 111002 Davis Furosemide 40mg 60 1 daily 2 4/27 111003 Davis Fosinopril 40mg 30 1 daily 2 4/27 111004 Wonder Glipizide XL 10mg 30 1 daily 5 4/27 111005 George Tramadol 50mg 60 1 bid 2

Patient Case: Additional Information Ethnicity: Caucasian PMHx: DM x 15 years; CAD x 10 years (MI in 1999 and 2001), heart failure, and osteoarthritis Social Hx: tobacco use OTC: aspirin 81mg daily, ibuprofen PRN BP: 144mmHg/85mmHg

Patient Case According to JNC 8, what is the BP target for this patient? < 140/90 mmhg What recommendations for therapy, if any, would you make in this patient? Provide patient education with regard to hypertension and drug therapy for this patient

Managing Elevated Cholesterol

What s New in 2013 Guidelines? Focus on reduction of cardiovascular risk: 4 statin benefit groups A new perspective on treatment goals Global risk assessment for primary prevention Safety recommendations

4 Defined Statin Benefit Groups Clinical ASCVD LDL >190 mg/dl Age 40-75 years + diabetes + LDL 70-189 mg/dl Age 40-75 + ASCVD 10 year risk of > 7.5% ASCVD = ACS, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease of atherosclerotic origin.

ASCVD Risk Assessment Use Pooled Cohort Risk Assessment Equations in non- Hispanic patients between age of 40 79 years Risk factors considered Sex Age Race Total Cholesterol HDL Systolic BP Treated for HBP Diabetes Smoker

Cholesterol Targets High-Intensity (LDL-C reduction > 50%) Age < 75 years + clinical ASCVD Age 40 75years + diabetes + ASCVD risk > 7.5% LDL-C > 190 mg/dl ASCVD > 7.5% Moderate-Intensity (LDL-C reduction 30 50%) Age > 75 years + clinical ASCVD Age 40 75 years + diabetes and ASCVD risk < 7.5%

Intensity of Statin Therapy High-intensity Moderate-intensity Low-intensity Daily dose lowers LDL-C on average, by ~ > 50% Atorvastatin 40 80mg Rosuvastatin 20-40mg Daily dose lowers LDL-C on average, by 30-50% Atorvastatin 10 20mg Rosuvastatin 5-10mg Simvastatin 20 40mg Pravastatin 40 80mg Lovastatin 40mg Fluvastatin 40mg BID Pitavastatin 2 4mg Daily dose lowers LDL-C on average, by < 30% Simvastatin 10mg Pravastatin 10 20mg Lovastatin 20mg Fluvastatin 20 40mg Pitavastatin 1mg Selection of statin and dose should be based on patient characteristics, level of ASCVD risk, patient preference, and potential for adverse drug reactions and drug interactions

Comparison of Statins Variable Rosuva- Atorva- Simva - Prava- Lova- Fluva- Pitava- Half-life (hrs) Protein Binding (%) Active Metab 13-20 7-14 2 1.8 5 1.2 12 88 >90 95 50 >95 >90 99 Yes Yes Yes No Yes No No Solubility Hydro- Lipo- Lipo- Hydro- Lipo- Lipo- Lipo- CYP 450 isoenzyme 2C9 2C19 3A4 3A4 --- 3A4 2C9 --- Adapted by Rosenson RS. The Am J of Med. 2004;116:408-416.

Statin Safety Concerns Hepatotoxicity Muscle adverse effects Myalgias = muscle aches, soareness, stiffness, tenderness, cramps Myopathy = muscle weakness Myositis = muscle inflammation; pain + CK elevation Myonecrosis +/- myoglobinuria or AKI Increased blood sugar? Cognitive adverse effects? Rosenson RS, et. al. J Clin Lipid. 2014;8:s58-71

Monitoring of Statin Therapy Liver enzymes at baseline and as clinically indicated thereafter Routine monitoring of CK and hepatic transaminase levels is not recommended

Nonstatin Therapy Drug Class Effects (% change) Safety Niacin LDL (15-30), HDL (15-35) TG (20-50) Fibric Acids LDL (5-20), HDL (10-35) TG (20-50) Flushing, BG, UA, GI upset, hepatotoxicity Dyspepsia, gallstones, myopathy Bile Acid sequestrants Cholesterol absorption inhibitor Omega-3-acid ethyl esters LDL (15 30%), HDL (3-5%), no significant effect on TG LDL( 14-18), HDL (1-3) TG (2) LDL, HDL, TG (17-48) GI distress, many DDI Headache, GI distress GI distress

Summary No longer use targets for cholesterol levels Identify patients at risk Know the 4 high risk groups Use medications proven to reduce risk, ie statins Encourage healthy lifestyle Understand that questions and concerns remain

Patient Profile 32 Patient Name: BE Address: 75 Dekalb Ave, Brooklyn, NY 11201 Age: 62 Height: 5 8 Weight: 251 lb Sex: F Phone: (800) 249-4957 Medication Profile Date Rx No. Physician Drug/Strength Qty Sig Refills 5/30 112555 Davis Carvedilol 25mg 60 1 bid 2 5/30 111002 Davis Furosemide 40mg 30 1 daily 2 5/30 111003 Davis Fosinopril 40mg 30 1 daily 1 5/30 111004 Wonder Glipizide XL 10mg 30 1 daily 4 5/30 111005 George Tramadol 50mg 60 1 bid 1 4/27 111001 Davis Carvedilol 12.5mg 60 1 bid 2 4/27 111002 Davis Furosemide 40mg 60 1 daily 2 4/27 111003 Davis Fosinopril 40mg 30 1 daily 2 4/27 111004 Wonder Glipizide XL 10mg 30 1 daily 5 4/27 111005 George Tramadol 50mg 60 1 bid 2

Patient Case: Additional Information Ethnicity: Caucasian PMHx: DM x 20 years; CAD x 15 years (MI in 1999 and 2001), heart failure, and osteoarthritis Social Hx: tobacco use OTC: aspirin 81mg daily, ibuprofen PRN BP: 144mmHg/85mmHg Total cholesterol = 195 mg/dl LDL = 120 mg/dl HDL = 45 mg/dl TG = 150 mg/dl

Patient Case According to AHA 2013 Document, would this patient benefit from statin therapy? If yes, recommend an appropriate lipid lowering regimen for this patient. Yes. Patient falls into a statin benefit group High-intensity statin: atorvastatin 40 80mg daily or rosuvastatin 20 40mg daily Provide patient education with regard to high cholesterol and drug therapy for this patient

Heart Failure Guidelines Update

What s new? Emphasis placed on education and transitions of care Broadened indication for the use of aldosterone antagonist Routine use of ACEI + ARB + ALDO ANT is harmful

Treatment Goals Identify and control risk factors for HF Improve quality of life Relieve/reduce signs and symptoms Prevent/minimize hospitalizations Slow progression of the disease process Prolong survival

Definition of Heart Failure Classification Ejection Description Fraction Heart Failure with Reduced Ejection Fraction (HFrEF) 40% Also referred to as systolic HF Heart Failure with Preserved Ejection Fraction (HFpEF) 50% Also referred to as diastolic HF. a. HFpEF, Borderline 41% - 49% b. HFpEF, Improved >40% A subset of patients with HFpEF previously had HFrEF with improvement or recovery in EF.

Classification of Heart Failure A B C ACCF/AHA Stages of HF At high risk for HF but without structural heart disease or symptoms of HF. Structural heart disease but without signs or symptoms of HF. Structural heart disease with prior or current symptoms of HF. I I NYHA Functional Classification No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. D Refractory HF requiring specialized interventions. III IV Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.

Non-Pharmacologic Therapy 40 Discontinue drugs that may aggravate HF Physical activity Stable patients only 20 45 minutes, 3 5 times per week Smoking cessation (if applicable) Vaccinations Annual influenza Pneumococcal Restrict dietary sodium Restrict fluid (< 2L/day) Avoid salt substitutes (ex. Nu-salt, Also Salt)

41 Drugs that May Precipitate or Exacerbate Heart Failure Antiarrhythmic agents: except amiodarone (Cordarone, Pacerone) and dofetilide (Tikosyn) Calcium channel blockers: verapamil (Calan SR, Isoptin SR, Covera HS, Verelan), diltiazem (Cardizem) Beta blockers Nonsteroidal anti-inflammatory drugs Rosiglitazone (Avandia)/Pioglitazone (Actos) Glucocorticoids Androgens and estrogens Chemotherapeutic agents: doxorubicin, daumomycin, cyclophosphamide Amphetamines

Treatment of Stage A HF 42 Identify and modify risk factors HTN Dyslipidemia DM Smoking cessation Limit alcohol consumption and illicit drug use Consider ACEI or ARB for patients with multiple risk factors

Treatment of Stage B HF 43 Therapy from stage A ACEI and BB for: Recent MI Reduced EF ARB (if intolerant to ACEI)

Treatment of Stage C HFrEF 44 Therapy for stage A and B Diuretics and salt restriction (if fluid retention) ACEI BB ARB (if intolerant to ACEI) Avoid drugs known to exacerbate HF Consider aldosterone antagonist, digoxin, and/or hydralazine/isosrbide dinitrate combination

Loop Diuretics 45 Furosemide (Lasix) Bumetanide (Bumex) Torsemide (Demadex) Usual daily dose 20 160 mg 0.5 4 mg 10 80 mg Ceiling dose 160 mg 2 mg 40 mg Bioavailability 10 100% 80-90% 80-100% Duration of effect 6 8 hrs 4 6 hrs 12 16 hrs Indicated for control of fluid overload Initiate at low dose Target weight decrease of 0.5 to 1 kg/day (until symptoms resolve) The appropriate chronic dose is that which maintains the patient at a stable dry weight without symptoms of dyspnea

Beta-Blockers 46 Recommended for all stable patients with no or minimal signs of fluid overload and reduced LVEF Benefits: Decrease mortality and slow disease progression Decrease hospitalizations Improvement in functional class May lead to symptomatic worsening or decompensation Use in combination with diuretics and ACEI

Beta-Blockers 47 Drug Initial Dose Target Dose Bisoprolol* 1.25mg daily 10mg daily Carvedilol 3.125mg BID 25-50 mg BID Carvedilol CR 10mg daily 80mg daily Metoprolol succinate CR/XL 12.5-25mg daily 200 mg daily Initiate low, double the dose every 2 weeks or as tolerated Patient should be clinically stable and euvolemic at time of initiation May take 2-3 months to see improvement in clinical response * Not FDA approved

Aldosterone Antagonist 48 Agents Spironolactone (Aldactone): 12.5 25mg daily Eplerenone (Inspra): 25-50mg daily Recommended for patients with NYHA Class III IV and LVEF < 35% or NYHA Class II + LVEF < 35% + history of CV hospitalization or elevated natriuretic peptide Adverse effects: hyperkalemia, gynecomastia Avoid concomitant use of NSAIDs, COX-2 inhibitors, high doses of ACEI or ARBs, potassium supplements, strong CYP3A4 inhibitors (eplerenone) DO NOT initiate if: GFR < 30 ml/min or SCr > 2.0 mg/dl in women or SCr> 2.5 mg/dl in men Potassium > 5 meq/l Triple therapy with ACEI + ARB + spironolactone is NOT routinely recommended

Isosorbide Dinitrate/Hydralazine 49 Shown to decrease mortality, hospitalization for HF, and quality of life in patients with symptomatic HF and decreased EF Should be considered: As an alternative to ACEI In addition to standard therapy in African American patients with symptomatic HF Dose: Hydralazine 25 75 mg QID + Isosorbide dinitrate 20 40mg QID Bidil (isosorbide dinitrate 20mg/Hydralazine 37.5mg): 1-2 tablets TID Adverse effects: Common: headache, dizziness, nausea, hypotension Severe: leukopenia, hepatotoxicity, lupus

Digoxin 50 Consider adding if: Stage C or D + reduced EF + persistent symptoms of HF despite therapy with ACEI, BB, and diuretic Chronic atrial fibrillation Dosing considerations Decrease dose in elderly and patients with decreased renal function Target serum concentrations 0.5 1 ng/ml Adverse effects: GI complaints Visual disturbances Cardiac arrhythmias

Treatment of Stage C HFpEF 51 Control underlying etiology of HF Use diuretics for pulmonary congestion and peripheral edema May use BB, ACEI, ARBs, or CCB to control symptoms Role for digoxin is not well established Aldosterone antagonists have not been studied in these patients Fluid and sodium restriction

Treatment of Stage D HF 52 Control fluid retention Fluid restriction Loop diuretic +/- thiazide like diuretic IV inotropic agents Non-pharmacologic measures Consider end-of life care Cardiac transplant Left-ventricular assist devices Intra-aortic balloon pump

Overview of Stages, Phenotypes and Treatment of HF At Risk for Heart Failure Heart Failure STAGE A At high risk for HF but without structural heart disease or symptoms of HF STAGE B Structural heart disease but without signs or symptoms of HF STAGE C Structural heart disease with prior or current symptoms of HF STAGE D Refractory HF e.g., Patients with: HTN Atherosclerotic disease DM Obesity Metabolic syndrome or Patients Using cardiotoxins With family history of cardiomyopathy Structural heart disease e.g., Patients with: Previous MI LV remodeling including LVH and low EF Asymptomatic valvular disease Development of symptoms of HF e.g., Patients with: Known structural heart disease and HF signs and symptoms Refractory symptoms of HF at rest, despite GDMT e.g., Patients with: Marked HF symptoms at rest Recurrent hospitalizations despite GDMT HFpEF HFrEF THERAPY Goals Heart healthy lifestyle Prevent vascular, coronary disease Prevent LV structural abnormalities Drugs ACEI or ARB in appropriate patients for vascular disease or DM Statins as appropriate THERAPY Goals Prevent HF symptoms Prevent further cardiac remodeling Drugs ACEI or ARB as appropriate Beta blockers as appropriate In selected patients ICD Revascularization or valvular surgery as appropriate THERAPY Goals Control symptoms Improve HRQOL Prevent hospitalization Prevent mortality Strategies Identification of comorbidities Treatment Diuresis to relieve symptoms of congestion Follow guideline driven indications for comorbidities, e.g., HTN, AF, CAD, DM Revascularization or valvular surgery as appropriate THERAPY Goals Control symptoms Patient education Prevent hospitalization Prevent mortality Drugs for routine use Diuretics for fluid retention ACEI or ARB Beta blockers Aldosterone antagonists Drugs for use in selected patients Hydralazine/isosorbide dinitrate ACEI and ARB Digoxin In selected patients CRT ICD Revascularization or valvular surgery as appropriate THERAPY Goals Control symptoms Improve HRQOL Reduce hospital readmissions Establish patient s endof-life goals Options Advanced care measures Heart transplant Chronic inotropes Temporary or permanent MCS Experimental surgery or drugs Palliative care and hospice ICD deactivation

Patient Education Symptom management Daily weight Sodium restriction Medication adherence Physical activity Modification of risk factors Follow-up appointments

Patient Case (Continued) 55 Three months later BE presents to your pharmacy with the following prescriptions from Dr. Wonder: Diovan 160mg, take 1 tablet PO daily, #30 Spironolactone 25mg, take 1 tablet PO daily, #30

Patient Profile 56 Patient Name: BE Address: 75 Dekalb Ave, Brooklyn, NY 11201 Age: 62 Height: 5 8 Weight: 251 lb Sex: F Phone: (800) 249-4957 Medication Profile Rx No. Physician Drug/Strength Qty Sig Refills 112555 Davis Atorvastatin 80mg 30 1 daily 3 112555 Davis Carvedilol 25mg 60 1 bid 2 111002 Davis Furosemide 40mg 30 1 daily 2 111003 Davis Fosinopril 40mg 30 1 daily 1 111004 Wonder Glipizide XL 10mg 30 1 daily 4 111005 George Tramadol 50mg 60 1 bid 1 111001 Davis Carvedilol 12.5mg 60 1 bid 2 111002 Davis Furosemide 40mg 60 1 daily 2 111003 Davis Fosinopril 40mg 30 1 daily 2 111004 Wonder Glipizide XL 10mg 30 1 daily 5 111005 George Tramadol 50mg 60 1 bid 2

Patient Case What concerns, if any, do you have regarding the new prescriptions for this patient? Provide patient education with regard to heart failure and drug therapy for this patient

Key Points: Heart Failure 58 Avoid factors known to exacerbate chronic HF Most patients with heart failure should be treated with an ACEI, BB, diuretic In patients with reduced EF and symptomatic HF despite standard therapy, consider: Isosorbide dinitrate/hydralazine (especially in African Americans) Aldosterone antagonist Digoxin ARBs For patients with preserved EF may use diuretics, BB, ACEI, ARBs, or CCBs Combine pharmacologic + non-pharmacologic therapy 58

Atrial Fibrillation Guidelines Update

What s new? Emphasis on shared decision making and individualization of therapy Increased emphasis on non-pharmacologic care Encourage the use of CHA 2 DS 2 -VASc vs. CHADS 2 score in stroke risk assessment Recommendations for use of dabigatran, rivaroxaban, and apixaban added Diminished role for aspirin use

Treatment Goals 61 Relieve symptoms Prevent thromboembolic complications Control ventricular rate Target resting HR < 80bpm May target resting HR < 110bmp if patient remains asymptomatic Restore and/or maintain normal sinus rhythm (NSR)

Stroke Prevention in Atrial Fibrillation 62 Patients with AF are at risk of cardioembolic stroke Risk of stroke increases with age and in presence of additional risk factors Consider antithrombotic therapy regardless of whether or not sinus rhythm is maintained Risk of thromboembolism AF > 48 hours = 15% rate of atrial thrombus AF > 72 hours = 30 % rate of atrial thrombus Thrombi present + cardioversion = 91% stroke rate Need for long-term antithrombotic therapy depends on assessment of risk of stroke

CHA 2 DS 2 - VASc Score Cardiac failure Hypertension A 2 ge (>75 years) Diabetes S 2 :stroke Vascular disease* Age 65-74 Sex category: female CHA 2 DS 2 VA Sc Score Stroke Rate 0 0 1 1.3% 2 2.2% 3 3.2% 4 4% 5 6.7% 6 9.8% *Vascular disease = CAD, myocardial infarction, peripherl artery disease, complex aortic plaque Lip GY, et. al. Chest 2010;137(2):263-272.

Stroke Prevention: Summary 64 Stroke Risk Category Low (CHA 2 DS 2 -VASc score= 0) Intermediate (CHA 2 DS 2 -VASc score= 1) High (CHA 2 DS 2 -VASc score > 2) Recommended Therapy No therapy Aspirin 81-325mg daily or warfarin (target INR 2-3) 1 st line: anticoagulant 2 nd line: aspirin + clopidogrel Stroke.ahajournals.org/content/early/2012/08/02SRT.0b01318266722

Comparison of Oral Anticoagulants 65 Warfarin (Coumadin) Dabigatran (Pradaxa) Rivaroxaban (Xarelto) Apixaban (Eliquis) MOA VKA DTI FXa inhibitor FXa inhibitor Dose Variable 150mg BID 20mg QD WF 5mg BID P-gp substrate No Yes Yes Yes Hepatic elimination Dosage adjust in renal insuf? CYP2C9 (major), CYP3A4, CYP2C19,ot hers Glucuronidation CYP3A4 CYP3A4 No Yes Yes Yes Half-life 20-60 hrs 12-17 hrs 5-9 hrs ~ 12 hrs

Comparison of Oral Anticoagulants 66 DDI Adverse effects Warfarin CYP2C9 and 3A4 inhibitors; antibiotics; vitamin K Bleeding, alopecia, skin necrosis, purple toe syndrome Dabigatran (Pradaxa) P-gp inducers and inhibitors; PPIs, H2 blockers Bleeding Dyspepsia Rivaroxaban (Xarelto) CYP3A4 and/or P-gp inhibitors Bleeding Apixaban (Eliquis) CYP3A4 and/or P-gp inhibitors Bleeding Monitoring INR --- --- --- Antidote Vitamin K --- --- ---

Patient Education: Anticoagulants Warfarin Take warfarin at the same time each day Avoid drugs or alcohol that can interact with warfarin Keep a diet containing vitamin K consistent Dabigatran Swallow capsules whole. DO NOT break, chew, or empty pellets from the capsule Dispense in the original container. Once open, use within 4 months May cause indigestion, stomach upset Do not take newer agent with grapefruit or grapefruit juice Do not D/C abruptly Notify a healthcare provider if any signs of bleeding, clotting, or stroke occur and of any upcoming surgery or procedure

Rate Control: Decision Algorithm 68 Paroxysmal or permanent A. Fib No HF, LVEF > 40% LVEF < 40% B-Blocker, CCB B-blocker, digoxin, amiodarone Assess HR control HR > 110 bpm: increase dose of initial drug or add second drug

69 Choosing an Anti-arrhythmic Agent to Maintain Sinus Rhythm Maintenance of sinus rhythm No Stuctural heart disease Coronary artery disease Heart Failure LVH Dronedarone* Flecainide Propafenone Sotalol Dofetilide Amiodarone Dofetilide Dronedarone* Sotalol Amiodarone NYHA Class III/IV Amiodarone Dofetilide *paroxysmal or persistent AF only

Safety Considerations in Maintenance of Sinus Rhythm Drug Caution/Exclude Pharmacokinetics Flecainide HF, CAD Metabolized by CYP2D6 Renally excreted Propafenone HF, CAD, liver disease, asthma Metabolized by CYP2D6 Inhibits P-glycoprotein and CYP2C9

Safety Considerations in Maintenance of Sinus Rhythm Drug Caution/Exclude Pharmacokinetics Amiodarone Lung disease, may prolong QT Inhibits many CYP enzymes and P-glycoprotein Dofetilide Dronedarone Sotalol Prolonged QT, renal disease, hypokalemia, diuretic therapy Bradycardia, HF, liver disease, may prolong QT Prolonged QT, renal disease, hypokalemia, diuretic therapy, HF Metabolized by CYP3A4 DDI with inhibitors of tubular secretion Metabolized by CYP3A4 Inhibits CYP3A4, CYP2D6, P-glycoprotein

Patient Case Three months later BE is diagnosed with atrial fibrillation. PMHx: DM x 20 years; CAD x 15 years (MI in 1999 and 2001), heart failure, and osteoarthritis Medications: spironolactone, atorvastatin, valsartan, carvedilol, tramadol, furosemide, and glipizide BP = 134/78 mmhg, HR = 78 bpm

Patient Case What is DA s CHA 2 DS 2 VASc Score? Recommend an antithrombotic agent for this patient to prevent thromboembolic complications. Provide patient education with regard to antithrombotic therapy for this patient

Summary 75 Treatment options to control rate are BB, CCB, digoxin, and amiodarone All patients need to be evaluated for risk of stroke. Most patients require therapy for stroke prevention Rhythm control is indicated in select patients to help control symptoms Amiodarone and dofetilide are preferred for patients with structural heart disease

Thank you!