Antiarrhythmic drug therapy

in HF with AF, what is

reasonable

Prof. Samir Rafla, FACC, FESC

Alexandria Univ.

smrafla@hotmail.com

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Recommendations for Use of

Dronedarone (Multaq) in Atrial

Fibrillation

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Class IIa

1.Dronedarone is reasonable to decrease

the need for hospitalization for

cardiovascular events in patients with

paroxysmal AF or after conversion of

persistent AF. Dronedarone can be

initiated during outpatient therapy.

(Level of Evidence: B

Recommendations for Use of

Dronedarone in Atrial Fibrillation

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Class III–Harm

1. Dronedarone should not be

administered to patients with class IV

heart failure or patients who have had an

episode of decompensated heart failure

in the past 4 weeks, especially if they

have depressed LV function (EF<35%).

(Level of Evidence: B)

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- The major adverse cardiac effects of

dronedarone are bradycardia and QT

prolongation. Torsades de pointes has

been reported.

- Like amiodarone, dronedarone inhibits

renal tubular secretion of creatinine,

which can increase plasma creatinine

levels. However, there is no reduction in

GFR.

- Dronedarone increases digoxin levels

1.7- to 2.5-fold.

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- Dronedarone is predominantly

metabolized by the liver (CYP3A4). It can

be administered with verapamil or

diltiazem, but low doses of these agents

should be used initially .

- Dronedarone does not alter the INR

when used with warfarin.

- The recommended oral dose of

dronedarone is 400 mg twice a day with

meals.

Dronedarone - Adverse Events

Stroke 4 (0.5) 3 (0.7) 0.69

Cough

Dyspnea

19 (2.3) 7(1.7) 0.67

Hyperthyroidism

Hypothyroidism

67/801 (8.4)

44/801 (5.5

56/396 (14.1)

14/396 (3.5)

0.002

0.15

Abnormal LFTs 100/822 (12.2) 55/404(13.6) 0.52

Elev of Serum

Creatinine 20 (2.4) 1 (0.2) 0.004

Bradycardia

Heart Failure

22 (2.7)

20 (2.4)

8 (2.2)

4 (1.0)

0.56

0.12

VARIABLE DRONEDARONE

N=828

PLACEBO

N=409 P value

Dronedarone - ATHENA: Summary

Dronedarone significantly prolongs time to first CV hospitalization or death in moderate- to high-risk AF patients

All-cause mortality was not increased in patients receiving dronedarone

CV mortality was lower in the dronedarone compared to the placebo group

The reduction in CV hospitalization was mainly due to fewer admissions for AF and acute coronary syndromes

The application of Dronedarone may be useful in low risk patients (only in NYHA Class I and II)

Hohnloser SH. Heart Rhythm Society 2008 Scientific Sessions;

May 15, 2008; San Francisco, CA.

Atrial Fibrillation and Acute Decompensated

Heart Failure

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Although the optimal resting HR during AF is

between 60 and 100 bpm, rates below 100 bpm

may not be achievable during AHDF until volume

overload and hypoxia have been corrected. A

more realistic target is to achieve a HR < 120

bpm during the first hours of treatment. Digoxin

should be the first rate-control agent considered.

If the patient has already been taking digoxin, add

doses only if serum digoxin concentration is <0.5

ng/mL.

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Cautious addition of small doses of an IV B blocker,

usually metoprolol in 2.5- to 5-mg increments or, if

systolic function is preserved, diltiazem will often be

required.

If rate control along with relief of volume overload

and dyspnea can be achieved, patients will

frequently revert back to SR if the AF episode is of

recent onset. If the patient does not improve with

these measures, meets anticoagulation criteria for

conversion, and if not already on an antiarrhythmic

drug, a trial of IV amiodarone may be helpful.

Atrial Fibrillation and Acute Decompensated

Heart Failure

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Amiodarone can be reloaded in patients already

on chronic, moderate doses (<200 mg daily) but

should not be added if the patient has been

taking another antiarrhythmic drug that prolongs

the QT interval, such as sotalol or dofetilide.

If this approach fails and heart rates during AF remain elevated, cardioversion after a period of loading with an antiarrhythmic drug, usually amiodarone, is the next step.

Pharmacological Cardioversion of AF of up to 7 Days

Duration

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Vernakalant IV or oral I

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Torsade de Pointes

Occurs in 1% of patients taking Amiodarone

Predisposing conditions

– LVH, congestive heart failure

– Bradycardia

– Hypokalemia

– Hypomagnesemia

– Digitalis therapy

– Baseline QT prolongation

– High drug concentration (except quinidine)

Patient Who Was Treated with Amiodarone for Atrial Fibrillation

Treatment of Torsade de Pointes

Remove offending

agent

Temporary ventricular

or atrial pacing

Isoproterenol

– Increases rate and

decreases QT

interval

Lidocaine

Mexiletine

Phenytoin

Magnesium

24 Porto-marina Beach - Egypt

Flecainide (Tambocor) & propafenone (Rythmol®) Toxicity and Cautions for Class IC Drugs:

- They are proarrhythmic drugs causing worsening of a preexisting arrhythmia or de novo occurrence of life-threatening ventricular tachycardia

- Notice: Class 1C drugs are particularly of low safety and have shown even to increase mortality when used chronically after MI.

With Sotalol (Betapace) and Dofetilide

(Tikosyn), the QT interval should be monitored

carefully during drug loading. Serum potassium

levels should also be watched carefully; in fact,

one should use torsades de pointes producing

agents with caution in patients requiring

potassium-wasting diuretics.

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Dofetilide (Tikosyn) had no effect on cardiac

output, cardiac index, or systemic vascular

resistance in patients with ventricular

tachycardia, mild to moderate congestive heart

failure .

Because increase in QT interval and the risk of

ventricular arrhythmias are directly related to

plasma concentrations of dofetilide, dosage

adjustment based on calculated creatinine

clearance is critically important

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28 Ras Sidr Beach. Saini. Egypt

Vernakalant is a sodium channel blocker (I

Na) and a potassium channel blocker.

In ACT study, adverse events were reported in

32% of placebo recipients and 38% of

Vernakalant recipients. No deaths or torsade

de points were reported.

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Atrial Specific AADs

Vernakalant BRINAVESS is contraindicated

in patients with severe aortic stenosis, systolic

BP<100 mm Hg, and heart failure class III and

IV.

Vernakalant is contraindicated in patients with

prolonged QT at baseline (uncorrected >440

msec), severe bradycardia, sinus node

dysfunction, or second-degree or third-degree

heart block in the absence of a pacemaker.

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Vernakalant is also contraindictated in patients

who use IV rhythm control antiarrhythmics

(class I and class III) within 4 hours prior to

administration of Vernakalant and patients with

acute coronary syndrome (including myocardial

infarction) within the last 30 days.

Adverse reactions (>5%) seen in the first 24

hours after receiving Vernakalant were taste

disturbance (20.1%), sneezing (14.6%), and

paraesthesia (9.7%).

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36 Ain Sokhna – Stella di Mare Hotel and Beach - Egypt