The medical letter on drugs and therapeutics july 7 2014

European guidelines recommend use of an oral anticoagulant for patients with a CHA2DS2-VASc score of 1, except for women with no other risk factor, for whom no antithrombotic therapy is

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on Drugs and Therapeutics Objective Drug Reviews Since 1959

IN THIS ISSUE

ISSUE

1433

Published by The Medical Letter, Inc • A Nonprofi t Organization

ISSUE No

1446

53

The treatment of atrial fi brillation includes

antico-agulation, rate control, and rhythm control New US

guidelines for the management of atrial fi brillation

have recently been published.1

ANTICOAGULATION

Atrial fi brillation increases the risk of thromboembolic

stroke Anticoagulant therapy reduces this risk, but it

can cause intracranial and other serious bleeding The

risk of bleeding must be weighed against the benefi t of

thromboembolic risk reduction

A new scoring system, the CHA2DS2-VASc score, has been

designed to aid in this assessment for patients with

non-valvular atrial fi brillation An algorithm from the recent US

guidelines recommends oral anticoagulant treatment for

patients who have a CHA2DS2-VASc score ≥2 For patients

with a CHA2DS2-VASc score of 0, who have a very low risk of

thromboemboli, it would be reasonable to omit

antithrom-botic therapy For patients with a CHA2DS2-VASc score

of 1, the US guidelines recommend no antithrombotic therapy or use of either aspirin or an oral anticoagulant, but evidence supporting use of aspirin for this indication

is limited European guidelines recommend use of an oral anticoagulant for patients with a CHA2DS2-VASc score of 1, except for women with no other risk factor, for whom no antithrombotic therapy is recommended.2

Patients with atrial fi brillation associated with a me-chanical valve, a bioprosthetic valve, prior mitral valve repair, or mitral stenosis should take warfarin

WARFARIN — When anticoagulation is indicated, the

benefi ts of long-term warfarin therapy in preventing ischemic stroke in patients with atrial fi brillation outweigh the risk of major bleeding

Dosing – The main drawback of warfarin has been the

need for close monitoring and dosage adjustment to keep the international normalized ratio (INR) between 2 and 3 The usual starting dosage range is 2-5 mg once daily, varying with the weight and age of the patient Algorithms are available at www.warfarindosing.org

Drug Interactions – Maintaining the INR in the desired

range is made more diffi cult by warfarin’s numerous interactions with food and with other drugs (see Table 2)

In patients with atrial fi brillation, the most important of these is with amiodarone, which decreases the warfarin dose requirement by one-third to one-half Another inter-action is with the widely used analgesic acetaminophen;

IN THIS ISSUE

ISSUE

1433

Volume 56

ISSUE No

Table 1 CHA 2 DS 2 -VASc Scoring

Condition Points

S Stroke, TIA, or thromboembolism 2

A Note to Our Readers

This is the fi rst issue of an enhanced version of The Medical Letter on Drugs and Therapeutics that will include reviews of new drugs like those traditionally found in The Medical Letter, reviews of drug classes like those published previously in Treatment Guidelines, and sometimes both Long-time subscribers may recall that for many years The Medical Letter included both types of reviews In 2002, to keep up with an increase in approvals

of new drugs, we spun off Treatment Guidelines as a separate publication Now the capability of pre-publishing

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on Drugs and Therapeutics Objective Drug Reviews Since 1959

Related article(s) since publication

Drug Interactions – Dabigatran etexilate is a substrate

of the efflux transporter P-glycoprotein (P-gp) Co-administration with P-gp inducers such as rifampin reduces serum concentrations of dabigatran and may decrease its effectiveness P-gp inhibitors such as amiodarone may increase serum concentrations of dabigatran.9

Reversibility – Unlike warfarin, which can be

re-versed by vitamin K, there is no specifi c antidote for dabigatran-induced bleeding Its anticoagulant effect

is not reversible except by hemodialysis

RIVAROXABAN – The factor Xa inhibitor rivaroxaban

is also FDA-approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial

fi brillation.10 It should not be used in patients with moderate or severe hepatic impairment

Reversibility – Due to the high percentage of drug

bound to protein in plasma, rivaroxaban is not expected

to be dialyzable Preliminary studies suggest that its anticoagulant effect may be reversed by prothrombin complex concentrate.11

Drug Interactions – Rivaroxaban is a substrate of

CYP3A4 and P-gp Coadministration of drugs that inhibit CYP3A4 and P-gp may increase serum concentrations

of rivaroxaban, leading to an increased risk of bleeding Coadministration of drugs that are inhibitors of P-gp and strong inhibitors of CYP3A4, such as ketoconazole, are contraindicated Coadministration of P-gp inducers and strong inducers of CYP3A4, such as rifampin, should also be avoided.9

APIXABAN – The factor Xa inhibitor apixaban is the

third new oral anticoagulant to be approved by the FDA for use in patients with nonvalvular atrial fi brillation

In clinical trials, apixaban was the only one of the new oral anticoagulants to cause less overall bleeding than warfarin, but the trials were conducted in somewhat different populations and used slightly different defi ni-tions of major bleeding.12 Apixaban should not be used

in patients with severe hepatic impairment

Reversibility – There is no established antidote to

reverse the anticoagulant effect of apixaban, which per-sists for about 24 hours after the last dose, and the drug

is not dialyzable Preliminary studies suggest that it may

be reversible with prothrombin complex concentrate.11

Drug Interactions – Apixaban is a substrate of CYP3A4

and P-gp The dose should be reduced to 2.5 mg twice daily if it is used concurrently with drugs that inhibit both CYP3A4 and P-gp, such as itraconazole, ritonavir,

occasional use of acetaminophen generally has little

or no effect on the INR in patients on chronic

warfa-rin therapy, but in some patients even a few grams of

acetaminophen can cause a dramatic increase in INR

Patients on chronic warfarin therapy who take more

than 2 g/day of acetaminophen for more than a few days

should be monitored closely for INR changes

NEWER ORAL ANTICOAGULANTS — In patients with

nonvalvular atrial fi brillation, dabigatran etexilate,

riva-roxaban, and apixaban all appear to be at least as

ef-fective as warfarin in preventing stroke, and in clinical

trials all caused less intracranial bleeding than

war-farin.3-5 Patients with atrial fi brillation associated with

a mechanical valve, a bioprosthetic valve, prior mitral

valve repair, or mitral stenosis should take warfarin

The three new oral anticoagulants do not require

rou-tine INR-type monitoring, have no dietary restrictions,

and may have fewer interactions with other drugs

compared to warfarin, but they have no established

method for determining the extent of anticoagulation,

have no specifi c antidote to reverse their

anticoagu-lant effect, and are not recommended for use in

pa-tients with end-stage kidney disease

DABIGATRAN – The oral direct thrombin inhibitor

dabigatran etexilate is FDA-approved for prevention

of thromboembolic stroke in patients with nonvalvular

atrial fi brillation.6

Bleeding Risk – Because of multiple spontaneous

reports of severe, sometimes fatal, bleeding with

dabigatran, the FDA conducted a post-marketing

study in >134,000 Medicare patients ≥65 years old

which found that the risks of intracranial bleeding and

ischemic and thromboembolic stroke were lower with

dabigatran than with warfarin, but the risk of major

gastrointestinal bleeding was higher with dabigatran.7,8

Table 2 Some Drugs that Interact with Warfarin

Anticoagulant Effect Anticoagulant Effect

Acetaminophen (Tylenol) Barbiturates

Amiodarone (Cordarone) Carbamazepine (Tegretol)

Cefazolin Cholestyramine (Questran)

Ceftriaxone (Rocephin) Dicloxacillin

Clarithromycin (Biaxin) Nafcillin

Erythromycin Phenytoin (Dilantin)

Fluconazole (Diflucan) Rifampin (Rifadin)

Fluoroquinolones St John’s wort

Fluorouracil Sucralfate (Carafate)

Fluoxetine (Prozac)

Fluvastatin (Lescol)

Fluvoxamine (Luvox)

Metronidazole (Flagyl)

Phenytoin (initial; Dilantin)

Rosuvastatin (Crestor)

Trimethoprim-sulfamethoxazole (Bactrim)

Voriconazole (Vfend)

or clarithromycin.9 Coadministration of drugs that

in-duce both CYP3A4 and P-gp, such as rifampin, should

be avoided

RATE CONTROL

Ventricular rate control is now widely used as fi rst-line

therapy for management of chronic atrial fi brillation

Antiarrhythmic drugs have not been shown to be

more effective in preventing serious complications

and have considerable toxicity.13 Lenient rate control

(resting heart rate <110 beats per minute), particularly

in patients with a structurally normal heart and no

heart failure, is easier to achieve and appears to be

as effective as strict rate control (resting heart rate

<80 beats per minute).14 The drugs most commonly

used for rate control in atrial fi brillation are listed in

Table 4

BETA-ADRENERGIC BLOCKERS — A beta-blocker

such as propranolol, metoprolol, or esmolol given

intravenously can acutely control the ventricular rate

in atrial fi brillation or flutter Oral beta-blockers are

used for long-term rate control Beta-blockers are

preferred over calcium channel blockers for patients

with coronary disease or systolic dysfunction They

should be used cautiously in patients with

decom-pensated heart failure

CALCIUM CHANNEL BLOCKERS — Verapamil and

diltiazem prolong AV nodal refractoriness and are effective in slowing the ventricular rate in atrial fi bril-lation or flutter Their IV use can be complicated by hypotension or bradycardia in patients with underlying heart disease, especially with concurrent use of other cardiodepressant drugs such as beta-blockers Verapamil and diltiazem may be preferred over beta-blockers for long-term use in patients with chronic obstructive pulmonary disease or asthma They should not be used in patients with decompensated heart fail-ure or Wolff-Parkinson-White syndrome

Unlike verapamil and diltiazem, dihydropyridine calcium channel blockers (all the other calcium channel blockers available in the US) generally have

no rate-controlling activity

AMIODARONE — More often used as a rhythm control

agent, IV amiodarone has been used for ventricular rate control in some critically ill patients, and oral amiodarone has been used when other treatments have failed to control heart rate

DIGOXIN — Generally used as an adjunctive agent,

digoxin can help control ventricular response in atrial fi brillation or flutter, but other drugs are more effective Digoxin, like verapamil and diltiazem,

Table 3 Oral Anticoagulants for Atrial Fibrillation

Warfarin Vitamin K 2-10 mg Long history of clinical experience Variability in dosage requirements

coagulant effect Numerous drug interactions Apixaban Direct factor 5 mg bid 3 Mortality benefi t over warfarin in No established method for determining 291.70

(Eliquis) Xa inhibitor one clinical trial the extent of anticoagulation

Causes less bleeding than warfarin No specifi c antidote for reversal Lower rates of ischemic stroke Not dialyzable

compared to warfarin Dose adjustment for age, weight, or Does not require INR monitoring renal impairment

Dabigatran Direct thrombin 150 mg bid 4 Lower rates of stroke and intra- No established method for determining 291.70 etexilate inhibitor cranial bleeding than warfarin in the extent of anticoagulation

Does not require INR monitoring Dose adjustment for renal impairment

Must be dispensed and stored in original container

Rivaroxaban Direct factor 20 mg Less intracranial and fatal bleeding No established method for determining 286.40

(Xarelto) Xa inhibitor once/d 5 than warfarin in one clinical trial the extent of anticoagulation

Does not require INR monitoring No specifi c antidote for reversal

Dose adjustment for renal impairment

1 Wholesale acquisition cost (WAC) of 30 days’ treatment at the lowest usual dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) June 5,

2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher.

2 Monitor and maintain INR in therapeutic range (2-3).

3 Dose is 2.5 mg bid for patients with 2 or more of the following: age >80 years, body weight <60 kg, or serum creatinine >1.5 mg/dL.

4 Dose is 75 mg bid for CrCl 15-30 mL/min, according to the US label The American College of Chest Physicians and Health Canada do not recommend use of the drug in patients with a CrCl <30 mL/min.

5 Taken with the evening meal Dose is 15 mg once daily for CrCl 15-50 mL/min.

has many interactions with other drugs (see Table 6) Dronedarone, a non-iodinated analog of amiodarone, has been less effective than amiodarone and has been associated with severe adverse effects, includ-ing increased mortality in patients with persistent atrial fi brillation.15

Propafenone and flecainide are generally reserved for patients with structurally normal hearts; they should only be used with a beta-blocker, verapamil,

or diltiazem Sotalol, a non-selective beta-blocker, is better tolerated than quinidine or some other older drugs now seldom used for this indication, but it in-creases the QT interval and can cause torsades de pointes; it should be avoided in patients with baseline

QT prolongation and in those receiving other drugs

should not be used in patients with

Wolff-Parkinson-White syndrome

RHYTHM CONTROL

The treatment of choice for urgent conversion of atrial

fi brillation is DC cardioversion Antiarrhythmic drugs,

particularly amiodarone, can be used to restore and

maintain normal sinus rhythm

DRUG THERAPY — The antiarrhythmic drugs most

commonly used now to prevent episodes of

paroxys-mal atrial fi brillation and to maintain sinus rhythm after

cardioversion are listed in Table 5

Amiodarone is the most effective antiarrhythmic

drug for maintenance of sinus rhythm, but it can

cause multiple adverse effects, some severe, and

Table 4 Some Rate Control Agents: Dosage and Adverse Effects

Beta-Adrenergic Blockers

Esmolol (Brevibloc, — IV : 500 mcg/kg bolus over 1 min, Heart block, hypotension, bradycardia,

Metoprolol (Lopressor, 50, 100 mg tabs; PO: 25-400 mg once/d or bid 2 Heart block, hypotension, bradycardia,

Toprol XL, and generics) 25, 50, 100, 200 mg IV : 2.5-5 mg over 2 min bronchospasm, depression

Propranolol (Inderal LA, 10, 20, 40, 60, 80 mg PO: 10-40 mg tid or qid 2 Heart block, hypotension, bradycardia, and others) tabs; 60, 80, 120, IV : 1 mg over 1 min (up to 3 bronchospasm, depression

Atenolol (Tenormin, 25, 50, 100 mg tabs PO: 25-100 mg once/d Bradycardia, depression, worsening of

Bisoprolol (Zebeta, 5, 10 mg tabs PO: 2.5-10 mg once/d Bradycardia, depression, worsening of

Carvedilol (Coreg, and 3.125, 6.25, 12.5, 25 mg PO: 3.125-25 mg bid Similar to other beta-adrenergic blockers,

Nadolol (Corgard, and 20, 40, 80 mg tabs PO: 10-240 mg once/d Bradycardia, depression, worsening of

Calcium Channel Blockers

Diltiazem (Cardizem LA, 30, 60, 90, 120 mg tabs; PO: 120-360 mg once/d or Heart block, hypotension, heart failure, and others) 120, 180, 240, 300, divided tid or qid 2 bradycardia, edema

Verapamil (Calan, 40, 80, 120 mg tabs; PO: 120-480 mg once/d or Heart block, hypotension, heart failure,

Calan SR, and others) 120, 180, 240 mg divided tid or qid 2 bradycardia, dizziness, headache,

ER tabs or caps IV : 0.075-0.15 mg/kg bolus over fatigue, edema, nausea, constipation

Amiodarone

Amiodarone (Cordarone, 100, 200 mg tabs 3 PO: 100-200 mg once/d Arrhythmias, nausea, vomiting, abnormal

Digoxin

Digoxin (Lanoxin, 0.125, 0.25 mg tabs PO: 0.125-0.25 mg once/d Bradycardia, AV block, arrhythmias,

ER = Extended-release

1 Dosage adjustment may be required for hepatic or renal impairment.

2 Dosage given as a range; dose and interval will vary depending on formulation used.

3 Cordarone is only available in 200-mg tablets.

that also prolong the QT interval.16 Disopyramide is

sometimes used to maintain normal sinus rhythm in

patients with vagally-induced atrial fi brillation

Dofeti-lide has been effective in patients with compromised

left ventricular function, but it requires in-hospital

dose titration and can cause torsades de pointes

CATHETER ABLATION — Radiofrequency catheter

ablation of the cardiac tissue causing an arrhythmia can restore sinus rhythm and may be superior to antiarrhythmic drugs in maintaining sinus rhythm and improving symptoms, exercise capacity, and quality of life.13 Complications are rare, but can be fatal

Table 5 Some Rhythm Control Agents: Dosage and Adverse Effects 1

Some Oral

Amiodarone 3

(Cordarone, and others) 100, 200 mg tabs4 PO: 400-600 mg daily in divided PO: Pulmonary fi brosis, bradycardia,

Disopyramide 5

(Norpace, and generics; 100, 150 mg caps; PO: 100-400 mg q6-12h 6 Anticholinergic effects (urinary retention,

Dofetilide 7

Dronedarone 8

Flecainide 9

Propafenone 9

(Rythmol, Rythmol SR, 150, 225, 300 mg tabs; PO: 150-425 mg q8-12h 6 Bradycardia, heart block, new ventricular

Sotalol 10

(Betapace, 80, 120, 160, 240 mg tabs 11 PO: 40-160 mg q12h Heart block, hypotension, bronchospasm,

ER = Extended-release

1 For maintenance of sinus rhythm All of these drugs require monitoring at initiation for proarrhythmias.

2 Dosage adjustment may be required for hepatic or renal impairment.

3 Should not be used in patients with cardiogenic shock or second or third degree AV block

4 Cordarone is only available in 200-mg tablets.

5 Should not be used in patients with cardiogenic shock, pre-existing second or third degree AV block, or congenital QT prolongation.

6 Dosage given as a range; dose and interval will vary depending on formulation used.

7 Available through a restricted distribution program Contraindicated in patients with long QT syndrome or severe renal impairment.

8 Should not be used in patients with NYHA class III or IV heart failure (HF) or permanent atrial fi brillation or in patients with decompensated HF in the past 4 weeks.

9 Should be used with a beta-blocker, verapamil, or diltiazem for cardioversion Should not be used in patients with coronary artery disease and signifi cant structural heart disease.

10 Should not be used in patients with bronchospasm, uncontrolled heart failure, long QT syndrome, sinus bradycardia, or second or third degree AV block

11 Betapace AF is not available in 240-mg tablets.

CONCLUSION

Anticoagulant therapy reduces the risk of

thrombo-embolic stroke in patients with atrial fi brillation, but

it can cause intracranial and other serious bleeding

The risk of bleeding must be weighed against the

benefi t of thromboembolic risk reduction Patients

with nonvalvular atrial fi brillation and a CHA2DS2

-VASc score ≥2 for risk of stroke should take either

warfarin or one of the newer oral anticoagulants

(apixaban, dabigatran, or rivaroxaban) Patients with

atrial fi brillation associated with a mechanical valve,

a bioprosthetic valve, prior mitral valve repair, or

mi-tral stenosis should take warfarin

Ventricular rate control is now widely used as

fi rst-line therapy for management of chronic atrial

fi brillation Lenient rate control (resting heart rate

<110 beats/minute) may be a reasonable alternative

to strict control (resting heart rate <80 beats/ minute)

A beta-blocker, verapamil, or diltiazem is generally

used for long-term rate control A beta-blocker is

pre-ferred for patients with coronary disease or systolic

dysfunction Verapamil or diltiazem may be preferred

over beta-blockers in patients with COPD or asthma

Amiodarone may be effective when other drugs have

failed to control ventricular rate

Antiarrhythmic drugs, particularly amiodarone, can

be used to restore and maintain normal sinus rhythm

The treatment of choice for urgent conversion of

atrial fi brillation is DC cardioversion Radiofrequency

catheter ablation of cardiac tissue responsible for

triggering or maintaining an arrhythmia can also

restore sinus rhythm ■

Table 6 Some Cardiovascular Drug Interactions with Amiodarone

Amlodipine (Norvasc, and others) Possible increased serum concentrations of amlodipine

Apixaban (Eliquis) Possible increased serum concentrations of apixaban

Atorvastatin (Lipitor, and generics) Possible increased risk of myopathy and rhabdomyolysis

Beta-adrenergic blockers Possible increased beta-blocker effect

Dabigatran (Pradaxa) Possible increased serum concentrations of dabigatran

Digoxin (Lanoxin, and others) Possible digoxin toxicity

Diltiazem (Cardizem, and others) Possible increased serum concentrations of amiodarone and/or diltiazem

Felodipine (Plendil, and generics) Possible increased serum concentrations of felodipine

Ibutilide (Corvert, and others) Possible QT interval prolongation

Isradipine Possible increased serum concentrations of isradipine; possible QT interval prolongation

Lovastatin (Mevacor, and others) Possible increased risk of myopathy and rhabdomyolysis

Nicardipine (Cardene, and others) Possible increased serum concentrations of nicardipine; possible QT interval prolongation

Nifedipine (Procardia, and others) Possible increased serum concentrations of nifedipine

Nisoldipine (Sular, and generics) Possible increased serum concentrations of nisoldipine

Rivaroxaban (Xarelto) Possible increased serum concentrations of rivaroxaban

Simvastatin (Zocor, and generics) Possible increased risk of myopathy and rhabdomyolysis

Sotalol (Betapace, and others) Possible QT interval prolongation and possible increased risk of bradycardia and sinus arrest

Verapamil (Calan, and others) Possible increased serum concentrations of amiodarone and/or verapamil

Warfarin (Coumadin, and others) Increased serum concentrations of warfarin

1 CT January et al 2014 AHA/ACC/HRS guideline for the man-agement of patients with atrial fi brillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society Circulation 2014 April 10 (epub).

2 AJ Camm et al 2012 focused update of the ESC guidelines for the management of atrial fi brillation: an update of the 2010 ESC guidelines for the management of atrial fi brillation Developed with the special contribution of the European Heart Rhythm Association Eur Heart J 2012; 33:2719.

3 SJ Connolly et al Dabigatran versus warfarin in patients with atrial fi brillation N Engl J Med 2009; 361:1139.

4 MR Patel et al Rivaroxaban versus warfarin in nonvalvular atrial

fi brillation N Engl J Med 2011; 365:883.

5 CB Granger et al Apixaban versus warfarin in patients with atrial fi brillation N Engl J Med 2011; 365:981.

6 Dabigatran etexilate (Pradaxa) – a new oral anticoagulant Med Lett Drugs Ther 2010; 52:89.

7 MR Southworth et al Dabigatran and postmarketing reports of bleeding N Engl J Med 2013; 368:1272.

8 FDA Pradaxa (dabigatran): drug safety communication – lower risk for stroke and death, but higher risk for GI bleeding com-pared to warfarin Available at http://www.fda.gov/safety/ medwatch/safetyinformation/safetyalertsforhumanmedical-products/ucm397179.htm Accessed June 26, 2014.

9 Inhibitors and inducers of CYP enzymes and P-glycoprotein Med Lett Drugs Ther 2013; 55:e44.

10 Rivaroxaban (Xarelto) – a new oral anticoagulant Med Lett Drugs Ther 2011; 53:65.

11 Kcentra: a 4-factor prothrombin complex concentrate for rever-sal of warfarin anticoagulation Med Lett Drugs Ther 2013; 55:53.

12 Apixaban (Eliquis) - a new oral anticoagulant for atrial

fi brillation Med Lett Drugs Ther 2013; 55:9.

13 SM Al-Khatib et al Rate- and rhythm-control therapies in pa-tients with atrial fi brillation: a systematic review Ann Intern Med 2014; 160:760.

14 IC Van Gelder et al Lenient versus strict rate control in patients with atrial fi brillation: a systemic review N Engl J Med 2010; 362:1363.

15 Safety of dronedarone (Multaq) Med Lett Drugs Ther 2011; 53:103

16 Combined list of all QTdrugs and the list of drugs to avoid for patients with congenital long QT syndrome Available at http://crediblemeds.org/everyone/composite-list-all-qtdrugs Accessed June 26, 2014.

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1 Explain the current approach to the management of a patient with atrial fi brillation including anticoagulation, rate control, and rhythm control strategies.

2 Discuss the pharmacologic agents available for prevention of thromboembolism in patients with atrial fi brillation and compare them based on their effi cacy, dosage and administration, drug interactions, and potential adverse effects.

3 Discuss the pharmacologic agents available for rate and rhythm control in patients with atrial fi brillation and compare them based on their effi cacy, dosage and administration, drug interactions, and potential adverse effects.

4 Determine the most appropriate therapy given the clinical presentation of an individual patient with atrial fi brillation

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Issue 1446 Questions

(Correspond to questions #1-10 in Comprehensive Exam #71, available January 2015)

6 Which of the following beta-blockers is not available in an oral formulation?

a metoprolol

b propranolol

c esmolol

d carvedilol

7 The treatment of choice for urgent conversion of atrial fi brillation

to normal sinus rhythm is:

a anticoagulation

b catheter ablation

c DC cardioversion

d digoxin

8 Adverse effects of amiodarone include:

a taste disturbances

b skin discoloration

c visual disturbances

d all of the above

9 Which of the following rhythm control agents should not be used

in patients with atrial fi brillation and signifi cant structural heart disease?

a propafenone

b amiodarone

c dofetilide

d dronedarone

10 The most effective drug available for maintenance of sinus rhythm is:

a sotalol

b amiodarone

c diltiazem

d dronedarone

1 A 72-year-old man with nonvalvular atrial fi brillation and a

CHA2DS 2 -VASc score of 2 asks you whether or not he needs to be

on anticoagulant therapy Considering the new US guidelines, which

of the following would you recommend?

a oral anticoagulation therapy

b no anticoagulation therapy

c aspirin

d none of the above

2 Which of the following oral anticoagulants is recommended for

patients with atrial fi brillation associated with a mechanical valve,

a bioprosthetic valve, prior mitral valve repair, or mitral stenosis?

a apixaban

b dabigatran etexilate

c rivaroxaban

d warfarin

3 A 65-year-old man with nonvalvular atrial fi brillation recently

saw advertisements for apixaban and rivaroxaban and asks

whether he should take one of the newer anticoagulants instead of

warfarin You could tell him that, compared to warfarin, apixaban,

rivaroxaban, and dabigatran etexilate:

a do not require routine INR-type monitoring

b have fewer interactions with other drugs

c cause less intracranial bleeding

d all of the above

4 Which of the following oral anticoagulants is a direct thrombin

inhibitor?

a warfarin

b dabigatran etexilate

c apixaban

d rivaroxaban

5 The drugs most commonly used for rate control in patients with

atrial fi brillation include:

a beta-blockers

b verapamil

c diltiazem

d all of the above

ACPE UPN: Per Issue Exam: 0379-0000-14-446-H01-P; Release: July 7, 2014, Expire: July 7, 2015 Comprehensive Exam 71: 0379-0000-15-071-H01-P; Release: January 2015, Expire: January 2016

EDITOR IN CHIEF: Mark Abramowicz, M.D.; EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School; EDITOR: Jean-Marie Pflomm, Pharm.D.; ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.; CONSULTING EDITORS: Brinda M Shah, Pharm.D.,

F Peter Swanson, M.D; SENIOR ASSOCIATE EDITOR: Amy Faucard

CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons; Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical

School; Eric J Epstein, M.D., Albert Einstein College of Medicine; Jane P Gagliardi, M.D., M.H.S., F.A.C.P, Duke University School of Medicine; Jules Hirsch, M.D., Rockefeller University; David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre; Richard B Kim, M.D., University of Western Ontario; Hans Meinertz, M.D., University Hospital, Copenhagen; Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine; Dan M Roden, M.D., Vanderbilt University School of Medicine; Esperance A.K Schaefer, M.D., M.P.H., Harvard Medical School; F Estelle R Simons, M.D., University of Manitoba; Neal H Steigbigel, M.D., New York University School of Medicine; Arthur M F Yee, M.D., Ph.D., F.A.C.R.,

Weill Medical College of Cornell University

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