2015 Pharmacotherapy Specialty Examination Review Course...

2015 Pharmacotherapy Specialty Examination Review Course: Cardiovascular Disease: Secondary Prevention Case #2

Christopher Betz, Pharm.D., BCPS, FKSHP, FASHP

Associate Professor, Sullivan University College of Pharmacy Clinical Pharmacy Specialist, Norton Audubon Hospital

Louisville, Kentucky

Learning Objectives At the conclusion of this session, given a patient case, the participant should be able to

• Correctly answer case-based questions about the appropriate treatment of a complex patient with multiple conditions, including heart failure, atrial fibrillation, and a thyroid disorder.

• Discuss safety issues in this population. • Formulate a plan to address barriers to patient education. • Identify and recommend appropriate resource organizations/groups to assist a specific patient.

Format: This session will use a series of audience response questions to engage the audience and to prepare participants to answer similar questions on a board certification examination. Premise: You are a clinical pharmacy specialist who splits his or her time between a transitional care clinic and an inpatient acute care teaching service. In both roles your job is to ensure the safe and effective transition of complicated patients from the hospital to home in an attempt to significantly reduce rates of readmission.

______________________________________________________________________________________________ ©2015 American Society of Health-System Pharmacists, Inc. All rights reserved.

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Cardiovascular Disease: Secondary Prevention Case #2 Date: March 2018 Initials BV

DOB/Age 59 yo

Sex M

Race/Ethnicity African American

Source Patient and medical records

Chief Complaint/History of Present Illness (CC/HPI) (including symptom analysis for CC): “Doc I’ve been really tired, achy, and a little short of breath. I’ve gained a few pounds and I’ve been having problems going to the bathroom. I also stopped taking that diabetes drug, because I didn’t think it was helping me and gave me a stomach ache.” BV reports to clinic today for a follow-up visit and lab check after being admitted to the hospital 1 month ago for acute decompensated heart failure. He claims to have missed his initial follow-up visit with us due to feeling run down. In the time since his hospitalization, BV reports that he’s gained some weight and feels fatigued, achy, and short of breath when walking up a flight of stairs. He also complains of constipation and decreased urination.

Past Medical History (major illnesses and surgeries) From Medical Record Hypertension Hyperlipidemia Pre-diabetes CKD stage II STEMI (2 years ago) GERD Heart Failure

Current Reported Prescription/OTC Medications Start Date Drug Name/Strength/Regimen Indication

Aspirin 81 mg orally once daily CAD/MI prevention Clopidogrel 75 mg orally once daily CAD/MI prevention Furosemide 40 mg orally once daily Heart failure Carvedilol 6.25 mg orally twice daily Heart Failure Lisinopril 20 mg orally once daily Heart Failure Eplerenone 25 mg orally once daily CAD/MI prevention Atorvastatin 80 mg orally once daily Hyperlipidemia/MI

prevention Pantoprazole 40 mg orally once daily GERD Nitroglycerin 0.3 mg SL prn chest pain Angina Docusate 100 mg orally twice daily prn Constipation Vaccinations: Influenza vaccine fall 2013 Pharmacy Used: Neighborhood

Pharmacy RX Payment: Private Insurance (prefers generic medications, unsure of what his copays are)

Meds Admin by: Self


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Drug Allergies/Adverse Effects: NKDA Family Medical History: Non-contributory

Social History

Residence: lives at home w/ wife Occupation: City worker (snow plow driver in winter and road worker all other times of year)

Smoking: Quit 2 years ago after smoking 1 ppd x 20 years

EtOH: He drinks 2-3 beers most days of the week

Illicit Drugs: Never Diet: Reports eating 3 meals per day and just eats what his wife cooks. Has not really kept track of how much salt he eats daily.

Education: High School graduate Social Environment: Lives with wife; has two grown sons and one daughter all of whom live in the area, but not with his him and his wife

Objective Data (observations/vital signs/physical examination/labs)

General: Pleasant male c/o malaise, constipation, and weight gain BP= 153/90 mm Hg Pulse= 70 bpm, regular T=97.5°F (oral) Height = 6’0” Weight = 207 lb BMI = 28.1 kg/m2 Remarkable physical findings: Lungs: Mild inspiratory and expiratory crackles ¼ of the way up both lung fields bilaterally Ext: Trace bilateral edema of both lower extremities Laboratory Tests

Glucose = 120 mg/dL

Na = 138 mEq/L K = 4.5 mEq/L Cl = 103 mEq/L HCO3 = 23 mEq/L NT-pro-BNP = 1000 pg/mL

BUN = 40 mg/dL SCr = 1.6 mg/dL eCrCl = 54.6 mL/min TSH = 19 mIU/L FT4 = 0.3 ng/dL From Hospital Discharge Height = 6’0” Weight = 200 lb BMI = 27.1 kg/m2 Laboratory Tests

Glucose = 120 mg/dL

Na = 138 mEq/L K = 4.5 mEq/L Cl = 104 mEq/L HCO3 = 24 mEq/L

BUN = 24 mg/dL SCr = 1.3 mg/dL eCrCl = 67 mL/min

Previous Studies

ECG: No ischemic changes

Echocardiogram: EF 30–35%


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Presentation Questions 1. Which of the following was the most likely culprit contributing to this patient’s current complaints,

physical exam findings, and abnormal lab test results? a. Drinking alcohol most days b. Eating fast food c. Failing to take prescribed medications d. Taking an OTC cold/pain preparation

2. Based upon his presentation what change should be made to the patient’s HF regimen at this time

to offer the best outcome? a. Discontinue carvedilol b. Discontinue lisinopril c. Increase furosemide to 40 mg bid d. Start digoxin 0.125 mg daily

3. Which of the following would the most appropriate starting daily dose of levothyroxine in this

patient? a. 25 mcg b. 50 mcg c. 100 mcg d. 150 mcg

4. Which of the following medications could be discontinued to reduce the pill burden and possibly

improve adherence? a. Aspirin b. Atorvastatin c. Clopidogrel d. Eplerenone

The case continues:

The patient’s clopidogrel, pantoprazole, and docusate are stopped

Upon calling his pharmacy it was revealed that he hadn’t filled either of his scheduled medications for the past 6 months

The patient returns to clinic 1 week later with no new complaints


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Current Medications Aspirin 81 mg po daily Furosemide 40 mg po BID Carvedilol 6.25 mg BID Lisinopril 20 mg po daily Eplerenone 25 mg po daily Atorvastatin 80 mg daily Levothyroxine 25 mcg po daily Prn Nitroglycerin 0.3 mg SL prn

Physical Exam: Crackles and edema have diminished Vitals BP: 150/83; HR: 89 ECG: normal sinus rhythm Previous echo: EF 30 – 35% Laboratory Data: Glucose = 121 mg/dL Na = 135 mEq/L K = 4.0 mEq/L Cl = 100 mEq/L HCO3 = 25 mEq/L BUN = 20 mg/dL SCr = 1.5 mg/dL eCrCl = 58.2 mL/min

5. Which of the following changes should be made to the treatment regimen at this time?

a. Discontinue aspirin b. Increase carvedilol to 12.5 mg bid c. Increase furosemide to 80 mg bid d. Increase lisinopril to 40 mg daily

6. Which of the following thyroid function tests and follow-up time frames should be recommended

for this patient at this time? a. TSH check in 1 week b. Free T4 check in 2 weeks c. TSH check in 4 weeks d. Free T4 check in 8 weeks

7. According to the EPHESUS and EMPHASIS-HF trials, when would be (or would have been) the time to

titrate this patient’s eplerenone dose? a. 1 week b. 2 weeks c. 4 weeks d. 8 weeks

The case continues: Unfortunately this patient was again lost to follow-up because of an insurance coverage change He comes back under our care again now as a Medicare patient at the age of 72 Chief complaint: New onset shortness of breath and palpitations “I feel like I have a butterfly in my chest”


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Current Medications Aspirin 81 mg po daily Furosemide 40 mg po BID Carvedilol 12.5 mg BID Lisinopril 30 mg po daily Eplerenone 50 mg po daily Atorvastatin 80 mg daily Levothyroxine 125 mcg po daily Prn Nitroglycerin 0.3 mg SL prn

Physical Exam: Crackles and edema have diminished Vitals BP: 155/92; HR: 129 ECG: irregularly, irregular rhythm Most recent echo: EF 25 – 30% Laboratory Data: Glucose = 112 mg/dL Na = 138 mEq/L K = 4.9 mEq/L Cl = 100 mEq/L HCO3 = 25 mEq/L BUN = 35 mg/dL SCr = 2.6 mg/dL eCrCl = 28.2 mL/min TSH = 0.1 mIU/L FT4 = 3.2 ng/dL

8. Which of the patient’s medications is contraindicated and must be discontinued at this time?

a. Atorvastatin b. Carvedilol c. Eplerenone d. Lisinopril

9. Which of this patient’s current medications could have contributed to atrial fibrillation?

a. Carvedilol b. Furosemide c. Levothyroxine d. Nitroglycerin

The case continues: The patient had not been taking his levothyroxine as directed until about 1 month ago The patient will be transferred to the hospital to manage his atrial fibrillation Levothyroxine was withheld and Endocrinology has been consulted 10. Which of the following represents the best management strategy for atrial fibrillation in this patient

at this time? a. Change carvedilol to IV metoprolol tartrate b. Change carvedilol to digoxin c. Initiate an amiodarone infusion d. Initiate a diltiazem infusion


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11. Once the patient’s atrial fibrillation symptoms diminish, which of the following is the most appropriate target resting heart rate? a. 50 bpm b. 70 bpm c. 90 bpm d. 110 bpm

12. Which of the following regimens is most safe and effective to prevent stroke in this patient?

a. Apixaban 5 mg PO BID b. Endoxaban 60 mg PO daily c. Dabigatran 75 mg PO BID d. Rivaroxaban 15 mg PO daily

13. If this patient does not respond to rate-controlling therapy, which of the following would be the best

option for rhythm control? a. Flecainide b. Dofetilide c. Dronedarone d. Sotalol


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References and Recommended Readings Heart Failure Management 1. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure.

Circulation. 2013; 128:e240-e327. http://circ.ahajournals.org/content/128/16/e240 (accessed 2013 Nov 1)

2. Heart Failure Society of America. HFSA 2010 comprehensive heart failure practice guideline. J Card

Fail. 2010; 16:e1-e194. http://www.heartfailureguideline.org/_assets/document/Guidelines.pdf (accessed 2012 July 07).

3. Hunt SA, Abraham WT, Chin MH et al. ACC/AHA 2005 guideline update for the diagnosis and

management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation . 2005; 112:e154-235. http://circ.ahajournals.org/content/112/12/e154.full.pdf (accessed 2012 April 16). (The 2005 guideline contains greater detail than the 2009 guideline since the latter is only a focused update. It also contains background information that is no longer included in the 2013 guideline by Yancy CW et al.).

4. Zannad F, McMurray JJ, Krum H et al. Eplerenone in patients with systolic heart failure and mild

symptoms. N Engl J Med. 2011; 364:11-21. (EMPHASIS-HF). http://www.ncbi.nlm.nih.gov/pubmed/21073363 (accessed 2012 July 07).

5. Poole-Wilson PA, Swedberg K, Cleland JG et al. Comparison of carvedilol and metoprolol on clinical

outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003; 362:7-13. http://www.courses.ahc.umn.edu/pharmacy/5822/lectures/comet.pdf (accessed 2014 May 21).

6. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial

in Congestive Heart Failure (MERIT-HF). Lancet. 1999; 353:2001-7. http://www.ncbi.nlm.nih.gov/pubmed/10376614 (accessed 2012 July 07).

7. Taylor AL, Ziesche S, Yancy C et al. Combination of isosorbide dinitrate and hydralazine in blacks with

heart failure. N Engl J Med. 2004; 351:2049-57. http://www.ncbi.nlm.nih.gov/pubmed/15533851 (accessed 2012 July 07).

Medications to Avoid in Heart Failure 1. Amabile CM, Spencer AP. Keeping your patient with heart failure safe. Arch Intern Med. 2004;

164:709-20. http://www.ncbi.nlm.nih.gov/pubmed/15078640 (accessed 2012 July 07). 2. Maxwell CB, Jenkins AT. Drug-induced heart failure. Am J Health-Syst Pharm. 2011; 68:1791-

804. http://www.ncbi.nlm.nih.gov/pubmed/21930637 (accessed 2012 July 07).


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http://circ.ahajournals.org/content/128/16/e240

http://www.heartfailureguideline.org/_assets/document/Guidelines.pdf

http://circ.ahajournals.org/content/112/12/e154.full.pdf

http://www.ncbi.nlm.nih.gov/pubmed/21073363

http://www.courses.ahc.umn.edu/pharmacy/5822/lectures/comet.pdf





Thyroid Disorders 1. Garber JR, Cobin RH, Gharib H et al. Clinical practice guidelines for hypothyroidism in adults:

cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012; 22:1200-35. http://www.thyroidguidelines.net/sites/thyroidguidelines.net/files/file/thy.2012.0205.pdf (accessed 2014 April 4).

2. Bahn RS, Burch HB, Cooper DS et al. Hyperthyroidism and other causes of thyrotoxicosis:

management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011; 21:593-646. https://www.aace.com/files/final-file-hypo-guidelines.pdf (accessed 2014 April 4).

Health Literacy 1. DeWalt DA, Callahan LF, Hawk VH et al. Health Literacy Universal Precautions Toolkit. (Prepared by

North Carolina Network Consortium, The Cecil G. Sheps Center for Health Services Research, The University of North Carolina at Chapel Hill, under Contract No. HHSA290200710014.) AHRQ Publication No. 10-0046-EF. Rockville, MD. Agency for Healthcare Research and Quality. April 2010. http://www.ahrq.gov/qual/literacy/healthliteracytoolkit.pdf (accessed 2012 July 07).

2. Health Literacy Measurement Tools. January 2009. Agency for Healthcare Research and Quality,

Rockville, MD. http://www.ahrq.gov/populations/sahlsatool.htm (accessed 2012 July 07). 3. Jacobson KL, Gazmararian JA, Kripalani S et al. Is Our Pharmacy Meeting Patients’ Needs? A

Pharmacy Health Literacy Assessment Tool User’s Guide. (Prepared under contract No. 290-00-0011 T07.) AHRQ Publication No. 07-0051. Rockville, MD: Agency for Healthcare Research and Quality. October 2007. http://www.ahrq.gov/professionals/quality-patient-safety/pharmhealthlit/pharmlit/index.html (accessed 2012 July 07).

Dual Antiplatelet Therapy After Drug-Eluting Stents 1. Mauri L, Kereiakes DJ, Yeh RW et al. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug

Eluting Stents. N Engl J Med. 2014;371:2155-66. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1409312 (accessed 2015 March 15)

2. Lee CW, Ahn JM, Park DW et al. Optimal duration of dual antiplatelet therapy after drug-eluting

stent implantation. Circulation. 2014; 129:304-12. http://www.ncbi.nlm.nih.gov/pubmed/24097439 (accessed 2014 April 04).

3. Park SJ, Park DW, Kim YH et al. Duration of dual antiplatelet therapy after implantation of drug-

eluting stents. N Engl J Med. 2010; 362:1374-82. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1001266 (accessed 2014 April 04).


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http://www.thyroidguidelines.net/sites/thyroidguidelines.net/files/file/thy.2012.0205.pdf

https://www.aace.com/files/final-file-hypo-guidelines.pdf

https://www.aace.com/files/final-file-hypo-guidelines.pdf

http://www.ahrq.gov/qual/literacy/healthliteracytoolkit.pdf

http://www.ahrq.gov/populations/sahlsatool.htm

http://www.ahrq.gov/professionals/quality-patient-safety/pharmhealthlit/pharmlit/index.html

http://www.ahrq.gov/professionals/quality-patient-safety/pharmhealthlit/pharmlit/index.html

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1409312


http://www.nejm.org/doi/pdf/10.1056/NEJMoa1001266

Atrial Fibrillation 1. January CT, Wann LS, Alpert JS et al. 2014 AHA/ACC/HRS guideline for the management of patients

with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014 Mar 28. Epub ahead of print. http://circ.ahajournals.org/content/early/2014/03/27/CIR.0000000000000041.full.pdf (accessed 2014 April 04).

2. Furie KL, Goldstein LB, Albers GW et al. Oral antithrombotic agents for the prevention of stroke in

nonvalvular atrial fibrillation. Stroke. 2012; 43:3442-53. http://stroke.ahajournals.org/content/43/12/3442.full.pdf (accessed 2014 April 04).

3. You JJ, Singer DE, Howard PA et al. Antithrombotic therapy for atrial fibrillation: antithrombotic

therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2 Suppl):e531S-75S. http://journal.publications.chestnet.org/data/Journals/CHEST/23443/112304.pdf (accessed 2014 April 04).

4. Sanoski CA. Overview of electrocardiographic findings and clinical presentation of common cardiac

arrhythmias. Am J Health-Syst Pharm. 2010; 67(9 Suppl 5):S5-10. http://www.ajhp.org/content/67/9_Supplement_5/S5.full.pdf (accessed 2014 April 04).

5. Heist EK, Mansour M, Ruskin JN. Rate control in atrial fibrillation: targets, methods,

resynchronization considerations. Circulation. 2011; 124:2746-55. http://circ.ahajournals.org/content/124/24/2746.full.pdf (accessed 2014 April 04).

6. Tsu LV, Dager WE. Safety of new oral anticoagulants with dual antiplatelet therapy in patients with

acute coronary syndromes. Ann Pharmacother. 2013; 47:573-7. http://www.ncbi.nlm.nih.gov/pubmed/23548645 (accessed 2014 April 04).


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http://circ.ahajournals.org/content/early/2014/03/27/CIR.0000000000000041.full.pdf

http://stroke.ahajournals.org/content/43/12/3442.full.pdf

http://journal.publications.chestnet.org/data/Journals/CHEST/23443/112304.pdf

http://www.ajhp.org/content/67/9_Supplement_5/S5.full.pdf

http://circ.ahajournals.org/content/124/24/2746.full.pdf


Christopher Betz, Pharm.D., BCPS, FKSHP, FASHP

Associate Professor

Sullivan University College of Pharmacy

Louisville, Kentucky

Cardiovascular Disease: Secondary Prevention Case # 2

Disclosures

• I have nothing to disclose related to the content of this presentation.

Learning Objectives

• Correctly answer case‐based questions about the appropriate treatment of a complex patient with multiple conditions, including heart failure, atrial fibrillation, and a thyroid disorder.

• Discuss safety issues in this population.

• Formulate a plan to address barriers to patient education.

• Identify and recommend appropriate resource organizations/groups to assist a specific patient.

Premise

You are a clinical pharmacy specialist who splits his or her time between a transitional care clinic and an inpatient acute care teaching service. In both roles your job is to ensure the safe and effective transition of complicated patients from the hospital to home in an attempt to significantly reduce rates of readmission.

Case

• 59 year old AA man

– Presents with dyspnea upon moderate exercise

– Was hospitalized for ADHF 1 month

—Missed first follow‐up visit because he was feeling “run down”

—“Doc I’ve been really tired, achy, and a little short of breath. I’ve gained a few pounds and I’ve been having problems going to the bathroom. I also stopped taking that diabetes drug, because I didn’t think it was helping me and gave me a stomach ache.”

Case

• Hypertension

• Hyperlipidemia

• Pre‐diabetes

• CKD stage II

• STEMI (2 years ago)

• GERD

• Heart Failure

• Aspirin 81 mg po daily• Clopidogrel 75 mg po daily• Furosemide 40 mg po daily• Carvedilol 6.25 mg BID• Lisinopril 20 mg po daily• Eplerenone 25 mg po daily• Atorvastatin 80 mg daily• Pantoprazole 40 mg daily• Nitroglycerin 0.3 mg SL prn • Docusate 100 mg po bid

prn

Past Medical History Reported Current Medications


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• Physical Exam:– Mild inspiratory and expiratory crackles

– 1+ bilateral edema of both lower extremities

– Weight: gained 7 lb. since hospital discharge

• Vitals– BP: 153/90 mm HG; HR: 70 bpm

– Temp: 97.5°F

• ECG: normal sinus rhythm

• Previous echo: EF 30 – 35%– Laboratory Data:

– NT‐pro‐BNP: 1000 pg/mL

– TSH: 19 mIU/L

– FT4: 0.3 ng/dL

– CrCl: 54.6 mL/min

138

4.5 23

103120

1.6

40

BMP at hospital discharge

Case

Question 1 Medication Reconciliation: Focusing on HFWhich of the following was the most likely culprit contributing to this patient’s current complaints, physical exam findings, and abnormal lab test results ?

a. Drinking alcohol most days

b. Eating fast food

c. Failing to take prescribed medications

d. Taking an OTC cold/pain preparation

HFSA Nonpharmacologic Treatment of HF

• Limit dietary sodium intake to 2‐3 g daily

• Limit fluid intake to < 2 L/day in patients with serum Na < 130 mEq/L– Consider in all patients with difficult‐to‐manage fluid retention

• Smoking cessation

• Limit alcohol consumption to ≤ 2 drinks per day in men or ≤ 1 drink per day in women– Patients with alcohol‐induced cardiomyopathy should abstain from alcohol

ACCF/AHA Nonpharmacologic Treatment of HF

• Alcohol– Unclear how much is a problem– Heavy use should be avoided– Patients with alcoholic cardiomyopathy should abstain from use

• Sodium restriction– Reasonable in symptomatic patients to reduce congestive symptoms (Level of evidence: C)

• Smoking cessation– Strong association with HF. Patients should be encouraged to quit

Yancy CW et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013; 128:e240-e327.

Heart Failure: Contributory Medications

• NSAIDS, COX 2 inhibitors, corticosteroids, thiazolidinediones, minoxidil, androgens & estrogens

• Antiarrhythmics (except amiodarone and dofetilide), CCBs (except amlodipine and felodipine), itraconazole, carbamazepine, TCAs, & cilostazol

• Amphetamines, cocaine, daunomycin, doxorubicin, & ethanol

Amabile CM, Spencer AP. Arch Intern Med. 2004; 164:709-20.Yancy CW et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013; 128:e240-e327.

Contributory Medications

• NSAIDs

– Mechanism: Sodium and water retention, diminished diuretic effect, & increased systemic vascular resistance

– Onset: days to 1 month

– Recommendation: Avoid the use of NSAIDs

– Pearls

—NSAID use = double risk of HF hospitalization

—Aspirin use in HF still remains controversialAmabile CM, Spencer AP. Arch Intern Med. 2004; 164:709-20.



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Question 1 Review

Which of the following was the most likely culprit contributing to this patient’s current complaints, physical exam findings, and abnormal lab test results?

a. Drinking alcohol most days

b. Eating fast food

c. Failing to take prescribed medications

d. Taking an OTC cold/pain preparation

Question 2Based upon his presentation what change should be made to the patient’s HF regimen at this time to offer the best outcome?

a. Discontinue carvedilol

b. Discontinue lisinopril

c. Increase furosemide to 40 mg bid

d. Start digoxin 0.125 mg daily

‐blocker Usage in HF• All patients with a left ventricular ejection fraction ≤ 40%

regardless of symptoms

• Decompensated Heart Failure

– New ‐blocker therapy—Optimize volume status, discontinue IV diuretics and vasoactive agents before initiation

– Continued ‐blocker therapy (patients already on a ‐blocker)

—Do not stop unless the patient develops cardiogenic shock, symptomatic bradycardia, or refractory volume overload

Heart Failure Society of America. HFSA 2010 J Card Fail. 2010; 16:e1-e194.

ACEI Usage in HF

• Recommended in all patients with HFrEF unless contraindicated to reduce morbidity and mortality (Class I; LOE A)

– Contraindications—Angioedema

— Pregnancy

– Precautions— Low blood pressure (SBP <80 mm Hg)

—Markedly increased serum creatinine (>3 mg/dL)

— Bilateral renal artery stenosis

— Elevated serum potassium (>5 mEq/L)


Diuretics

• Recommended to maintain normal volume status in volume‐overloaded patients

• Diuretics are necessary adjuncts in heart failure management when symptoms are caused by sodium and/or fluid retention

• Offer symptomatic relief, but no mortality benefit


Are all Diuretics Equally Efficacious in Heart Failure?

• ↑ Na excre on by 20%‐25%

• Increase free water clearance

• Maintain effects unless renal function is significantly impaired

Hunt SA et al. Circulation. 2005; 112:e154-235.

• ↑ Na excre on by 5%‐10%

• Decrease free water clearance

• Lose effectiveness in patients with impaired renal function

Loops Thiazides


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Digoxin Usage in Heart Failure

• Digoxin can be beneficial in patients with systolic HF unless contraindicated, to decrease hospitalizations(Class IIa; LOE B)

• Consider use in patients with continuous symptoms despite guideline determined medical therapy (GDMT)

• Commonly dosed at 0.125 to 0.25 mg daily

– Do not load in HF

– Ideal plasma concentration 0.5 to 0.9 ng/mL



Potential Digoxin Complications

• Digoxin Toxicity (> 2 ng/mL)

— Cardiac arrhythmias

—GI complaints

— CNS manifestations

– Toxicity can occur at lower levels due to:

— Low K or Mg levels

—Hypothyroidism

—Drugs

– Amiodarone, dronedarone, verapamil, clarithromycin, erythromycin

– Poor renal function can also elevate digoxin levels


Question 2 Review

Based upon his presentation what change should be made to the patient’s HF regimen at this time to offer the best outcome?

a. Discontinue carvedilol

b. Discontinue lisinopril


d. Start digoxin 0.125 mg daily

Question 3Which of the following would the most appropriate starting daily dose of levothyroxinein this patient?

a. 25 mcg

b. 50 mcg

c. 100 mcg

d. 150 mcg

Primary Hypothyroidism Management

• All patients with a TSH > 10 mIU/L should be treated with levothyroxine – Patients under 50 years of age without coronary heart disease (CHD):—may be started on 1.6 mcg/kg/day

– Ideal body weight should be used for dosing

– Patients ≥ 50 years of age:—without CHD may be started on doses of 50 mcg daily

—with known CHD, the usual starting dose is reduced to 12.5–25 mcg/day.

Garber JR et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012; 22:1200-35.

Patient Safety/Education

• Patients should utilize the same l‐thyroxine preparation with each refill

– Contact the prescriber if changed

• The use of dietary supplements and nutraceuticals for thyroid support is not recommended

• Instruct patients to take their l‐thyroxine preparation 30 – 60 minutes before breakfast with water or at bedtime 4 hours after the last meal

Garber JR et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012; 22:1200-35.


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Health Literacy: Improving Communication

• Greet patients with a smile and maintain eye contact

• Speak slowly

• Use nonmedical language

• Limit information

– 3‐5 key points

– Need‐to‐know only

• Repeat key points

• Utilize graphics

– Draw pictures, use models, or illustrations

• Encourage patient participation

– Ask and elicit questions

• Teach‐back

DeWalt DA et al. Health Literacy Universal Precautions Toolkit. AHRQ Publication No. 10-0046-EF Rockville, MD. Agency for Healthcare Research and Quality. April 2010.

Resources For Patients with Thyroid Disorders

• American Thyroid Association – www.thyroid.org

• Thyroid Federation International– www.thyroid‐fed.org

• Hormone Foundation – www.hormone.org

• Magic Foundation (support and education to families of children with growth disorders)– www.magicfoundation.org

Question 3 Review

Which of the following would the mostappropriate starting daily dose of levothyroxinein this patient?

a. 25 mcg

b. 50 mcg

c. 100 mcg

d. 150 mcg

Question 4Which of the following medications could be discontinued to reduce the pill burden and possibly improve adherence?

a. Aspirin

b. Atorvastatin

c. Clopidogrel

d. Eplerenone

Duration of DAPT:Primary PCI for STEMI

O’Gara PT et al. Circulation. 2013; 127:529–55.

P2Y12 inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (BMS or DES) during primary PCI using the following maintenance doses:

• Clopidogrel 75 mg daily; or

I IIa IIb III

• Prasugrel 10 mg daily; or

• Ticagrelor 90 mg twice a day

I IIa IIb IIIContinuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing DES placement.

DAPT after DES

Trial DES LATE1 REAL‐LATE2

N 2531 2514 1357 1344

Therapies DAPT Aspirin 100‐200mg/day

DAPT Aspirin 100‐200mg/day

MI or Death from (cardiac

causes)

2.6%P = 0.75

2.4% 1.8%P = 0.17

1.2%

Major Bleeding 1.4%P = 0.20

1.1% 0.2P = 0.35

0.1

Trial Duration 24 months 24 months

All patients received at least 12 months of DAPT prior to randomization

Lee CW, Ahn JM, Park DW et al. Optimal Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation. Circulation. 2014; 129:304-12.

Park SJ, Park DW, Kim YH et al. Duration of Dual Antiplatelet Therapy after Implantation of Drug-Eluting Stents.

N Engl J Med 2010; 362:1374-82.


15

Question 4 Review

Which of the following medications could be discontinued to reduce the pill burden and possibly improve adherence?

a. Aspirin

b. Atorvastatin

c. Clopidogrel

d. Eplerenone

The Case Continues:

• The patient’s clopidogrel, pantoprazole, and docusate are stopped

– Upon calling his pharmacy it was revealed that he hadn’t filled either of his scheduled medications for the past 6 months

• The patient returns to clinic 1 week later with no new complaints

• Current Medications– Aspirin 81 mg po daily

– Furosemide 40 mg po BID

– Carvedilol 6.25 mg BID

– Lisinopril 20 mg po daily

– Eplerenone 25 mg po daily

– Atorvastatin 80 mg daily

– Levothyroxine 25 mcg podaily

• Prn

– Nitroglycerin 0.3 mg SL prn

• Physical Exam:

– Crackles and edema have diminished

• Vitals

– BP: 150/83; HR: 89

• ECG: normal sinus rhythm

• Previous echo: EF 30 – 35%

• Laboratory Data:

– CrCl: 58.2

135

4.0 25

100121

1.5

20

Question 5 Follow‐up VisitWhich of the following changes should be made to the treatment regimen at this time?

a. Discontinue aspirin

b. Increase carvedilol to 12.5 mg bid


d. Increase lisinopril to 40 mg daily

ACE inhibitor Dosing in Heart Failure

Drug Initial Dose Target Dose

Captopril 6.25 mg TID 50 mg TID

Enalapril 2.5 mg twice daily 10 ‐ 20 mg twice daily

Fosinopril 5 ‐10 mg Daily 40 mg Daily

Lisinopril 2.5 ‐ 5 mg Daily 20 ‐ 40 mg Daily

Perindopril 2 mg Daily 8 ‐ 16 mg Daily

Quinapril 5 mg twice daily 20 mg twice daily

Ramipril 1.25 ‐ 2.5 mg Daily 10 mg Daily

Trandolapril 1 mg Daily 4 mg Daily

Heart Failure Society of America. J Card Fail. 2010; 16:e1-e194.


‐blocker Benefits in HF

• Ejection fraction

• Symptoms


• Norepinephrine‐induced hypertrophy and cardiac ischemia

• Hospitalizations

• The need to increase dosages of other heart failure medications

• Mortality

Improves Decreases


16

‐blocker Dosing in Heart FailureDrug Initial Dose Target Dose

Bisoprolol 1.25 mg daily 10 mg daily

Carvedilol IR 3.125 mg twice daily 25 – 50 mg twice daily*

Carvedilol CR 10 mg daily 80 mg daily

Metoprolol succinate XL 12.5 mg daily 200 mg daily

Heart Failure Society of America. J Card Fail. 2010; 16:e1‐e194.

* Maximum recommended dosage 25 mg PO twice daily for patients < 85 kg and 50 mg PO twice daily for patients > 85 kg

Question 5 Follow‐up Visit

Which of the following changes should be made to the treatment regimen at this time?

a. Discontinue aspirin

b. Increase carvedilol to 12.5 mg bid


d. Increase lisinopril to 40 mg daily

Question 6 Thyroid follow‐upWhich of the following thyroid function tests and follow‐up time frames should be recommended for this patient at this time?

a. TSH check in 1 week

b. Free T4 check in 2 weeks

c. TSH check in 4 weeks

d. Free T4 check in 8 weeks

Primary Hypothyroidism Monitoring

• Dose adjustments should be guided by TSH levels (primary hypothyroidism only)

• TSH levels should be drawn 4 – 8 weeks following:– Initiation of therapy– Dosage changes– Changes in l‐thyroxine preparation

• Once TSH levels have normalized and a dosage is established, levels may be drawn at 6 months and then annually

Garber JR et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid.

2012; 22:1200-35.

Question 6 Review

Which of the following thyroid function tests and follow‐up time frames should be recommended for this patient at this time?

a. TSH check in 1 week

b. Free T4 check in 2 weeks

c. TSH check in 4 weeks

d. Free T4 check in 8 weeks

Question 7According to the EPHESUS and EMPHASIS‐HF trials, when would be (or would have been) the time to titrate this patient’s eplerenone dose?

a. 1 week

b. 2 weeks

c. 4 weeks

d. 8 weeks


17

EMPHASIS‐HF

• Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF)

• Explored adding an aldosterone antagonist to standard therapy in patients with systolic heart failure and mild symptoms– 2737 patients with NYHA class II heart failure and an ejection fraction ≤ 35% were randomized to receive eplerenone or placebo

Zannad F, McMurray JJ, Krum H et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. N Engl J Med. 2011; 364:11-21.

EMPHASIS‐HF

• Results– Compared with placebo eplerenone decreased risk of death and hospitalizations in patients with mild symptoms

• Dose Titration Schedule– Started at 25 mg daily and increased to 50 mg daily at 4 weeks—Or started on 25 mg every 48 hr and increased to 25 mg daily if CrCl was 30 – 49 ml/min (potassium must be <5 mmol/L)

Zannad F, McMurray JJ, Krum H et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. N Engl J Med. 2011; 364:11-21.

Aldosterone Antagonist Dosing In HF

Drug Initial Dose Target Dose

Spironolactone 12.5 mg QD 25 mg QD

Eplerenone 25 mg QD 50 mg QD

Yancy CW et al. Circulation 2013; 128:e240-e327.

Question 7 Review

According to the EPHESUS and EMPHASIS‐HF trials when would be (or would have been) the ideal time to titrate this patient’s eplerenone dose?

a. 1 week

b. 2 weeks

c. 4 weeks

d. 8 weeks

The Case Continues:

• Unfortunately this patient was again lost to follow‐up because of an insurance coverage change

• He comes back under our care again now as a Medicare patient at the age of 72

• Chief complaint

– New onset shortness of breath and palpitations

– “I feel like I have a butterfly in my chest”

• Vitals– BP: 155/92; HR: 129

• ECG: irregularly, irregular rhythm

• Most recent echo: EF 25–30%

• Laboratory Data:– CrCl: 29 mL/min

– TSH = 0.1 mIU/L

– FT4 = 3.2 ng/dL

138

4.9 25

100112

2.5

35

• Current Medications

– Aspirin 81 mg po daily

– Furosemide 40 mg po daily

– Carvedilol 12.5 mg po BID

– Lisinopril 30 mg po daily

– Eplerenone 50 mg po daily

– Atorvastatin 80 mg daily

– Levothyroxine 125 mcg podaily

• Prn

– Nitroglycerin 0.3 mg SL prn


18

Question 8 Safety ConcernsWhich of the patient’s medications is contraindicated and must be discontinued at this time?

a. Atorvastatin

b. Carvedilol

c. Eplerenone

d. Lisinopril

Class III: Harm

• The inappropriate use of aldosterone antagonists is potentially harmful due to life‐threatening hyperkalemia or renal insufficiency when:

– serum creatinine is > 2.5 mg/dL in men

– serum creatinine is > 2.0 mg/dL in women

– estimated GFR < 30 mL/min

– serum potassium is > 5.0 mEq/L

Yancy CW et al. Circulation 2013; 128:e240-e327.

Question 8 Review

Which of the patient’s medications is contraindicated and must be discontinued at this time?

a. Atorvastatin

b. Carvedilol

c. Eplerenone

d. Lisinopril

Atrial Fibrillation Characteristics

• Rapid, disorganized atrial contraction– 400 – 600 beats per minute

• Random electrical impulses through the AV node results in random contraction of the ventricles– 120 – 180 beats per minute

• ECG– Irregular R‐R interval

– No P waves

Sanoski CA. Am J Health-Syst Pharm. 2010; 67(9 Suppl 5):S5-10.

Sanoski CA. Am J Health-Syst Pharm. 2010; 67(9 Suppl 5):S5-10.

Atrial Fibrillation ECG CharacteristicsQuestion 9Which of this patient’s current medications could have contributed to atrial fibrillation?

a. Carvedilol

b. Furosemide

c. Levothyroxine

d. Nitroglycerin


19

Ancillary Inducers of AFib

• Valvular Heart Disease

• CAD

– MI

• Heart Failure

• Hypertension

• Cardiomyopathy

• Cor pulmonale

Fuster V et al. Circulation. 2006; 114:e257-354.

• Alcohol

• Pulmonary Embolism

• Hyperthyroidism

• Surgery

• Electrocution

• Obesity

• Obstructive sleep apnea

• Drugs (stimulants)

Cardiac Other

Question 9 Review

Which of this patient’s current medications could have contributed to atrial fibrillation?

a. Carvedilol

b. Furosemide

c. Levothyroxine

d. Nitroglycerin

The Case Continues:

• The patient had not been taking his levothyroxine as directed until about 1 month ago– Of note:

—TSH = 0.1 mIU/L, FT4 = 3.2 ng/dL

• The patient will be transferred to the hospital to manage his atrial fibrillation– Levothyroxine was withheld and Endocrinology has been consulted

Question 10Which of the following represents the best management strategy for atrial fibrillation in this patient at this time?

a. Change carvedilol to IV metoprolol tartrate

b. Change carvedilol to digoxin

c. Initiate an amiodarone infusion

d. Initiate a diltiazem infusion

Atrial Fibrillation ManagementAtrial Fibrillation:

General Principles of Management• Step 1: Rate control acutely

– Prevent hemodynamic instability

• Step 2: Determine long‐term strategy

– Rate control vs. Rhythm control

• Thromboembolic stroke prevention

– Determine stroke risk

– Anticoagulation therapy vs. antiplatelet therapy


20

Step 1: Initial Management

Fuster V et al. Circulation. 2006; 114:e257-354.

SymptomaticHemodynamically

StableInitial Treatment

No YesAV‐node blocking agents oral

route

Yes YesAV‐node blocking agents

intravenous route

Yes No Direct current cardioversion

Rate versus Rhythm Control

• Both offer similar:– Mortality rates

– Ischemic stroke rates

• Rate control– Preferred in older less symptomatic or asymptomatic patients

— Typically easier then rhythm control

—Generally less adverse effects

• Rhythm control– Preferred in patients who remain symptomatic despite attempts at

rate control

—Greater rates of hospitalization

—Greater numbers of adverse events

Heist EK, Mansour M, Ruskin JN. Circulation. 2011; 124:2746-55.

Rate Control

• AV Node

– Beta‐blockers

– Nondihydropyridine CCBs

– Digoxin

– Amiodarone


Question 10

Which of the following represents the best management strategy for atrial fibrillation in this patient at this time?

a. Change carvedilol to IV metoprolol tartrate

b. Change carvedilol to digoxin

c. Initiate an amiodarone infusion

d. Initiate a diltiazem infusion

Question 11 Once the patient’s atrial fibrillation symptoms diminish, which of the following is the most appropriate target resting heart rate?

a. 50 bpm

b. 70 bpm

c. 90 bpm

d. 110 bpm

Rate Control Parameters

• Target Heart Rate– Target HR (2006)

—60 to 80 bpm at rest—90 to 115 bpm with moderate exercise1

– New Target HR (2011‐2013)—< 110 bpm at rest in patients with stable LV function2

– Stable = EF > 40%

—60 to 70 bpm at rest in patients with AF & CHF3

– Sort of New Target (2014)—< 80 bpm at rest (Class IIa: LOE B)— < 110 bpm at rest in patients with stable LV function (Class IIb: LOE B)4 Fuster V et al. Circulation. 2006; 114:e257-354.

Anderson JL et al. Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations). J Am Coll Cardiol. 2013; 61(18):1935-44.


January CT et al. Circulation. 2014 Mar 28. Epub ahead of print.


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RACE II Trial

• Lenient versus Strict Rate Control in Patients with Atrial Fibrillation

– N = 614

– Patients with permanent atrial fibrillation were randomized to one of two rates:

—lenient rate‐control = < 110 bpm

—strict rate‐control = < 80 bpm

– Lenient control was found to be as effective as strict rate control and was easier to achieve

Van Gelder IC, Groenveld HF, Crijns HJ et al. Lenient versus Strict Rate Control in Patients with Atrial Fibrillation. N Engl J Med. 2010; 365:1363-73.

Question 11 Review

Once the patient’s atrial fibrillation symptoms diminish, which of the following is the most appropriate target resting heart rate?

a. 50 bpm

b. 70 bpm

c. 90 bpm

d. 110 bpm

Question 12Which of the following regimens is most safe and effective to prevent stroke in this patient?

a. Apixaban 5 mg PO BID

b. Endoxaban 60 mg PO daily

c. Dabigatran 75 mg PO BID

d. Rivaroxaban 15 mg PO daily

CHADS2 versus CHA2DS2‐VASc

CHADS2 (1,2)

CHF 1

Hypertension 1

Age ≥ 75 1

Diabetes 1

Stroke/TIA 2

Maximum score = 6

Furie KL et al. Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation. Stroke. 2012; 43:3442-53.

You JJ et al. Chest. 2012; 141(2 Suppl):e531S-75S.


CHA2DS2‐VASc (3)

CHF 1

Hypertension 1

Age ≥ 75* 2

Diabetes 1

Stroke/TIA 2

Vascular disease (prior MI, PAD, aortic plaque)

1

Age 65 – 74* 1

Sex (female sex) 1

Maximum score = 9

What the guidelines say…

• Score = 0 (low risk)– CHEST believes aspirin is the best choice– ACCF/AHA no treatment would be fine– AHA/ASA think no treatment would be fine

• Score = 1 (intermediate risk)– CHEST prefers anticoagulant, but could use aspirin + clopidogrel in patients

without concerns of major bleeding– AHA/ASA no treatment or aspirin– ACCF/AHA no treatment, aspirin, or anticoagulant

• Score ≥ 2 (high risk)– CHEST recommends an anticoagulant, but could use aspirin + clopidogrel in

patients who can’t take an anticoagulant for reasons other then major bleeding

– AHA/ASA recommends an anticoagulant– ACCF/AHA recommends anticoagulant


Meschia JF et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2014 Dec; 45(12):3754-832.

You JJ et al. Chest. 2012; 141(2 Suppl):e531S-75S.

Study Patients Patient Characteristics

ASA Dose

Primary Endpoint

Results p Value

SPAF1 1330 Age: 61‐757% prior stroke

325 mgdaily

Stroke or SE ASA 3.6%Pbo: 6.3%

0.02

AFASAK 1007 Age: 74 (mean)1.6% prior stroke

75mgdaily

Stroke or SE ASA: 5.5%Pbo: 5.5%

NS

LASAF 285 Age: 62 (mean)0% prior stroke

125 mg(qd or qod)

Stroke, CV events, death

ASA: 2.6%Pbo: 3.3%

NS (0.07)

JAST 871 Age: 65 (mean)2.5% prior stroke

150‐200 mg daily

CV Death, TIA, brain infarct

ASA: 6.3%Pbo: 5.1%

NS (0.458)

EAFT 1007 Age: 73 (mean)100% prior stroke

300mg daily

Vascular Death, nonfatal MI or stroke, SE

ASA: 15%Pbo: 19%Strokes only:ASA:10%/yrPbo: 12%/yr

NS

SPAF Investigators. Circulation. 1991; 84:527-39.

ONLY 1 POSITIVE TRIAL: SPAF 1, 1991: 325mg/day ASASE = Systemic embolism

Evidence For Aspirin in Atrial Fibrillation: Placebo Trials


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Is there a place for aspirin + clopidogrel in AF?

• ACTIVE W (N = 6706)– Clopidogrel 75 mg/day +

aspirin 75‐100 mg/day versus warfarin

– Composite of stroke, non CNS embolus, MI, and vascular death

– Stopped early due to significant events in the clopidogrel + aspirin group

– Major bleeds similar (p=0.53)– Minor bleeds were

significantly higher in the antiplatelet group (p=0.0009)

• ACTIVE A (N = 7554 who were not candidates for warfarin)– Clopidogrel 75 mg/day +

aspirin 75‐100 mg/day versus placebo

– Composite of stroke, non CNS embolus, MI, and vascular death

– Over 3.6 years aspirin + clopidogrel significantly reduced major vascular events (p=0.01)

– Aspirin + clopidogrel had a significantly higher incidence of major hemorrhage (p<0.001)

Connolly S, Pogue J, Hart R et al. Lancet. 2006; 367(9526):1903–12.

Connolly SJ, Pogue J, Hart RG et al. N Engl J Med. 2009; 360(20):2066–78.

NOAC Package Insert Dosing For AFDrug Dose Renal adjustment

Apixaban 5 mg PO BID 2.5 mg PO BID for patients with 2 of the following: Age ≥ 80 Weight ≤ 60 kgSerum creatinine ≥ 1.5 mg/dL

Dabigatran 150 mg PO BID 75 mg PO BID for CrCl 15 ‐ 30 mL/min

Rivaroxaban 20 mg PO daily with evening meal

15 mg PO daily for CrCl 15 – 50 mL/minGive with evening meal

Endoxaban 60 mg PO daily for patients with a CrCl > 50 to ≤ 95 mL/min

30 mg PO daily for CrCl 15 – 50 mL/min

Eliquis PI. Princeton, NJ: Bristol-Meyers Squibb Company; 2012 Dec.

Pradaxa PI. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2013 Apr.

Xarelto PI. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2013 Mar.

Savaysa PI. Tokyo, Japan: Daiichi Sankyo Co., LTD.; 2015 Jan.

Novel Anticoagulants in AF

Trial RE‐LY ARISTOTLE ROCKET‐AF

Drug WarfarinDabigatran 110 mg BID

Dabigatran 150 mg BID

WarfarinApixaban 5 mg BID

WarfarinRivaroxaban 20 mg daily

S or SE annually

1.69%1.53%p<0.001

noninferior

1.11%p<0.001superior

1.60%1.27%p=0.01superior

2.2%1.7%

p=<0.001noninferior

MB annually

3.36%2.71%p=0.003

3.11%p=0.31

3.09%2.13%p<0.001

3.4%3.6%p=0.58

Excluded for renal function

CrCl < 30 mL/minCrCl < 25 mL/min or

Cr > 2.5 mg/dLCrCl < 30 mL/min

Renaldosing

None

2.5 mg PO BID for 2 of the following:Age ≥ 80, wt ≤ 60kgCr ≥ 1.5 mg/dL

15 mg PO daily for CrCl of 30 – 49 mL/min

Connolly SJ, Ezekowitz MD, Yusuf S et al. N Engl J Med. 2009; 361:1139-51.

Granger CB, Alexander JH, McMurray JJV et al. N Engl J Med. 2011; 365:981-92.

Patel MR, Mahaffey KW, Garg J et al. N Engl J Med. 2011; 365:883-91.

S = stroke; SE = systemic embolism; MB = major bleeding

Novel Anticoagulants in AF

Trial ENGAGE AF‐TIMI 48

Drug Warfarin Endoxaban 30 mg daily Endoxaban 60 mg daily

S or SE annually 1.50%1.61%p=0.005

noninferior

1.18%p<0.001

noninferior

MB annually 3.43%1.61%p<0.001

2.75%p<0.001

Excluded for renal function

CrCl < 30 mL/min

Renal Dosing

For both endoxaban groups the dosage was halved for any of the following:CrCl 30 – 50 mL/minWt ≤ 60kgConcomitant use of verapamil, quinidine, or dronedarone

Giugliano RP, Ruff CT, Braunwald E et al. N Engl J Med. 2013; 369:2093-2104.


Secondary Analysis of ARISTOTLECrCl > 80 mL/min (41%) 50 ‐ 80 mL/min (42%) < 50 mL/min (17%)

Drug Apixaban Warfarin Apixaban Warfarin Apixaban Warfarin

S or SE annually 0.99% 1.12% 1.24% 1.69% 2.11% 2.67%

MB annually 1.46% 1.84% 2.45% 3.21% 3.21% 6.44%

Patients on low dose apixaban

0% 1.3% 24.3%

Hohnloser SH, Hijazi Z, Thomas L et al. Eur Heart J. 2012; 33:2821-30.

Hazard Ratio(95% CI)0.74

(0.56, 0.97)


(0.62, 0.94)


(0.38, 0.66)


Secondary Analysis of ROCKET‐AF

CrCl ≥ 50 mL/min 30 ‐ 49 mL/min

Drug Rivaroxaban 20 mg/day Warfarin Rivaroxaban 15 mg/day Warfarin

S or SE annually

1.57% 2.00% 2.32% 2.77%

MB annually

3.39% 3.17% 4.49% 4.70%

Fox KAA, Piccini JP, Wojdyla D et al. Eur Heart J. 2011; 32:2387-94.


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Ongoing Trial

• Dabigatran

– Study in Nonvalvular Atrial Fibrillation Patients With Severely Impaired Renal Function

—Recruiting

—Dose = 75 mg PO BID

—Inclusion

– ≥ 18 years of age

– Nonvalvular AF with an indication for anticoagulation

– CrCl 15 ‐ 30 mL/min by the Cockcroft‐Gault

Pradaxa Study in Non-valvular Atrial Fibrillation Patients With Severely Impaired Renal Function. ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT01896297?term=dabigatran+and+renal&rank=2 Accessed May 21, 2014.

Question 12 Review

Which of the following regimens is most safe and effective to prevent stroke in this patient?

a. Apixaban 5 mg PO BID

b. Endoxaban 60 mg PO daily

c. Dabigatran 75 mg PO BID

d. Rivaroxaban 15 mg PO daily

Dual NOA/antiplatelet therapy

• RE‐LY– ~ 40% were on aspirin– 5% were on clopidogrel

• ROCKET‐AF– Excluded dual antiplatelet therapy and aspirin doses > 100 mg/day

— ~ 36% were on aspirin

• ARISTOTLE– Excluded dual antiplatelet therapy and aspirin doses > 165 mg/day

— ~ 30% were on aspirin— ~ 2% were on clopidogrel

• ENGAGE‐AF‐TIMI 48– Excluded dual antiplatelet therapy

— ~29% were on aspirin

• No data exists on the use of NOAs in combination with prasugrel or ticagrelor Tsu LV, Dager WE. Ann Pharmacother. 2013; 47:573-7.

Connolly SJ, Ezekowitz MD, Yusuf S et al. N Engl J Med. 2009; 361:1139-51.

Granger CB, Alexander JH, McMurray JJV et al. N Engl J Med. 2011; 365:981-92.

Patel MR, Mahaffey KW, Garg J et al. N Engl J Med. 2011; 365:883-91.

Giugliano RP, Ruff CT, Braunwald E et al. N Engl J Med. 2013; 369:2093-2104.

Question 13If this patient does not respond to rate‐controlling therapy, which of the following would be the best option for rhythm control?

a. Flecainide

b. Dofetilide

c. Dronedarone

d. Sotalol

Classification of Antiarrhythmic Drugs

Class Drugs Primary Ion Blocked

Ia QuinidineProcainamideDisopyramide

SodiumIb LidocaineMexiletine

Ic FlecainidePropafenone

II Beta‐blockers Calcium

III AmiodaroneDofetilideDronedaroneSotalolIbutilide

Potassium

IV VerapamilDiltiazem

Calcium

Rhythm Control: Cardioversion

• Pharmacologic cardioversion– Dofetilide, flecainide,

ibutilide, propafenone, amiodarone

• Direct current cardioversion (DCC)– Amiodarone, flecainide,

ibutilide, propafenone, or sotalol may utilized prior to DCC to enhance effects

• Preventing thromboembolism– Anticoagulation with

warfarin (INR 2‐3) for AF ≥ 48 hrs or unknown duration

— Apixaban, dabigatran, or rivaroxaban may be used as an alternative

— 3 weeks prior & 4 weeks after cardioversion

– Utilize heparin in ptswith hemodynamic instability



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Maintenance of Sinus Rhythm in Patients with Heart Failure

• 1st Line

– Amiodarone

– Dofetilide

• 2nd Line

– Catheter ablation


FDA Label Changes for Dronedarone

• “Healthcare professionals should not prescribe Multaq to patients with AF who cannot or will not be converted into normal sinus rhythm (permanent AF), because Multaq doubles the rate of cardiovascular death, stroke, and heart failure in such patients.”

• “Healthcare professionals should monitor heart (cardiac) rhythm by electrocardiogram (ECG) at least once every 3 months. If the patient is in AF, Multaq should be stopped or, if clinically indicated, the patient should be cardioverted.”

• “Multaq is indicated to reduce hospitalization for AF in patients in sinus rhythm with a history of non‐permanent AF (known as paroxysmal or persistent AF)”

• “Patients prescribed Multaq should receive appropriate antithrombotic therapy.”

FDA Drug Safety Communication: Review update of Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events 12-10-11. http://www.fda.gov/Drugs/DrugSafety/ucm283933.htm#sa

Question 13 Review

If this patient does not respond to rate‐controlling therapy, which of the following would be the best option for rhythm control?

a. Flecainide

b. Dofetilide

c. Dronedarone

d. Sotalol

Resources For Patients with Atrial Fibrillation

• StopAfib.org– http://www.stopafib.org/resources.cfm

• American Heart Association – Afib Resources & FAQ

—https://www.heart.org/HEARTORG/Conditions/Arrhythmia/AboutArrhythmia/AFib‐Resources‐and‐FAQ_UCM_423786_Article.jsp

• Heart Rhythm Society– http://www.hrsonline.org/Patient‐Resources/Heart‐Diseases‐Disorders/Atrial‐Fibrillation‐AFib#axzz2xxPsLdii


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