3 million Americans 160,000 new cases each year 16 million by 2050 90% of patients have...

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3 million Americans 160,000 new cases each

year 16 million by 2050 90% of patients have

recurrences Incremental cost = $26

billionJACC 2004; 43(1): 47-52.Circ 2006; 114: 119-125.

Circ Cardiovasc Qual Outcomes 2011; 4(3): 313-20.

RATE CONTROL

RHYTHMCONTROL

STROKE PREVENTION

An 84 year old woman with HTN presents for routine follow-up of long-standing atrial fibrillation. She is active and asymptomatic. She is on Toprol 100 mg daily and warfarin. Her resting HR is irregular and 97, blood pressure 110/68. Her exam is otherwise normal. What should you do next?

A. Continue current therapy. B. Increase her Toprol to 150 mg daily.

C. Start dronedarone 400 mg bid.D. Add digoxin 0.125 mg daily.E. Refer for DCCV.

An 84 year old woman with HTN presents for routine follow-up of long-standing atrial fibrillation. She is active and asymptomatic. She is on Toprol 100 mg daily and warfarin. Her resting HR is irregular and 97, blood pressure 110/68. Her exam is otherwise normal. What should you do next?

A. Continue current therapy. B. Increase her Toprol to 150 mg daily.

C. Start dronedarone 400 mg bid.D. Add digoxin 0.125 mg daily.E. Refer for DCCV.

Rest heart rate ≤ 80 bpm. 24-hr Holter average ≤ 100 bpm. 6-min walk HR ≤ 110 bpm.

NEJM. 347(23): 2002.

614 patients with permanent atrial fibrillation

Strict vs. lenient rate control: < 80 bpm vs. < 110 bpm

Noninferiority trial 1˚ EP: death from cardiovascular causes,

hospitalization from CHF, CVA, systemic embolization, bleeding and life threatening arrhythmic events

Follow-up: 2-3 years

Dyspnea, fatigue or palpitations 45.6% vs. 46.0%

Avg HR: 94±9 vs. 76±12

Paroxysmal <7 daysPersistent >7 daysPermanent >12 months

A 52 year old man with atrial fibrillation and mild LV systolic dysfunction presents with recurrent atrial fibrillation and heart failure despite multiple attempts at DCCV followed by trials of dofetilide and amiodarone. Vitals: HR 68, BP 120/80 . What should you do next?

A. Titrate heart failure medications, nothing further can be done for the atrial fibrillation. B. Refer for AV node ablation and pacemaker placement.

C. Start dronedarone 400 mg bid.D. Cardiovert and refer for catheter ablation

(pulmonary vein isolation).

A 52 year old man with atrial fibrillation and mild LV systolic dysfunction presents with recurrent atrial fibrillation and heart failure despite multiple attempts at DCCV followed by trials of dofetilide and amiodarone. Vitals: HR 68, BP 120/80 . What should you do next?

A. Titrate heart failure medications, nothing further can be done for the atrial fibrillation. B. Refer for AV node ablation and pacemaker placement.

C. Start dronedarone 400 mg bid.D. Cardiovert and refer for catheter ablation

(pulmonary vein isolation).

A 52 year old man with atrial fibrillation and mild LV systolic dysfunction presents with recurrent atrial fibrillation and heart failure despite multiple attempts at DCCV followed by trials of dofetilide and amiodarone. Vitals: HR 68, BP 120/80 . What should you do next?

A. Titrate heart failure medications, nothing further can be done for the atrial fibrillation. B. Refer for AV node ablation and pacemaker placement.

C. Start dronedarone 400 mg bid.D. Cardiovert and refer for catheter ablation

(pulmonary vein isolation).

1˚ EP (recurrence or premature study drug discontinuation): 74% vs 55%

Atrial fibrillation recurrence 63.5% vs. 42% Premature discontinuation 10.4% vs. 13.3%

J Cardiovasc Electrophysiol 2010; 21: 597-605.

DAFNE: to determine the most appropriate loading dose for prevention of AF after DCCV

Fre

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Resting HRExertional

HR

4628 patients: dronedarone 400 mg bid vs placebo

1˚ EP: 1st hospitalization due to CV events or death

Mean f/u 21 months

Rx discontinuation: 30.2% vs 30.8%

> 70 years oldhypertension

diabetes mellitusprior TIA/CVA/embolization

LA diameter ≥50 mmLVEF ≤ 40%

Multi-national, RDBPC trial comparing placebo to dronedarone in patients with permanent atrial fibrillation

Inclusion criteria: > 65 years old with history of embolization, myocardial infarction, ASCAD, prior CHF or >75 years old/HTN/DM.

Exclusion criteria: class IV or unstable class III CHF Composite endpoint: MACE (stroke, systemic

arterial embolization, MI, cardiovascular death), cardiovascular hospitalization and all-cause mortality

Target enrollment: 10,800 patients

Stopped at 3149 patients significant increase in cardiovascular events in patients taking dronedarone

(Permanent Atrial fibriLLAtion outcome Study using dronedarone)

Hypothesis: Dronedarone will reduce the rate of hospitalization due to heart failure and possibly also reduce mortality by reducing arrhythmia.

Inclusion Criteria: Class III-IV CHF or PND with LVEF ≤ 35%

Exclusion Criteria: Acute pulmonary edema <12 hours prior Recent myocardial infarction Planned or recent cardiac surgery or

angioplasty

Planned enrollment: 1000 patients Terminated after a median follow-up of 2

months

HR 2.13; 95% CI: 1.07 to 4.25, p =0.03

A 52 year old man with atrial fibrillation and mild LV systolic dysfunction presents with recurrent atrial fibrillation and heart failure despite multiple attempts at DCCV followed by trials of dofetilide and amiodarone. Vitals: HR 68, BP 120/80 . What should you do next?

A. Titrate heart failure medications, nothing further can be done for the atrial fibrillation. B. Refer for AV node ablation and pacemaker placement.

C. Start dronedarone 400 mg bid.D. Cardiovert and refer for catheter ablation

(pulmonary vein isolation).

A 52 year old man with atrial fibrillation and mild LV systolic dysfunction presents with recurrent atrial fibrillation and heart failure despite multiple attempts at DCCV followed by trials of dofetilide and amiodarone. Vitals: HR 68, BP 120/80 . What should you do next?

A. Titrate heart failure medications , nothing further can be done for the atrial fibrillation. B. Refer for AV node ablation and pacemaker placement.

C. Start dronedarone 400 mg bid.D. Cardiovert and refer for catheter ablation

(pulmonary vein isolation).

…...

www.atrialfibrillationablation.org

www.aafp.org

Multicenter, prospective, randomized, open-label clinical trial

Hypothesis: Percutaneous LACA for the purpose of eliminating atrial fibrillation is superior to current state-of-the-art therapy with either rate control or rhythm control drugs.

Inclusion criteria: paroxysmal or persistent atrial fibrillation with stroke/TIA or one or more risk factors

1˚ Endpoint: total mortality Follow-up: minimum of 2 years

A 76 year old male with HTN and diabetes presents with the new diagnosis of atrial fibrillation, discovered on a preoperative EKG for cataract surgery. He is active and asymptomatic. Medications include Toprol and Metformin. His resting heart rate is well controlled. What do you advise to decrease his risk for stroke?

A. No additional treatment is necessary.

B. Start ASA 325 mg daily.

C. Start ASA 81 mg daily and Plavix 75 mg daily.

D. Begin warfarin.

E. Jantoven, dabigatran or rivaroxaban should be started.

www.med.umich.edu

otm.oxfordmedicine.com

A 76 year old male with HTN and diabetes presents with the new diagnosis of atrial fibrillation, discovered on a preoperative EKG for cataract surgery. He is active and asymptomatic. Medications include Toprol and Metformin. His resting heart rate is well controlled. What do you advise to decrease his risk for stroke?

A. No additional treatment is necessary.

B. Start ASA 325 mg daily.

C. Start ASA 81 mg daily and Plavix 75 mg daily.

D. Begin warfarin.

E. Jantoven, dabigatran or rivaroxaban should be started.

Low risk = ASA

High Risk = AC

*Vascular disease = prior MI, aortic plaque or peripheral vascular disease

*

Anticoagulation for scores ≥ 2

1° Endpoint: stroke, systemic embolization, myocardial infarction or vascular death

Hypothesis: The addition of clopidogrel to ASA will reduce the risk of vascular events.

1° Endpoint: stroke, systemic embolization, myocardial infarction or vascular death

7,554 patients, median follow-up 3.6 years

1° Endpoint: stroke, systemic embolization, myocardial infarction or vascular death

FDA NEWS RELEASE : 19 OCT 2010FDA approves Pradaxa to prevent stroke in

patients with ATRIAL FIBRILLATION

A 76 year old male with HTN and diabetes presents with the new diagnosis of atrial fibrillation, discovered on a preoperative EKG for cataract surgery. He is active and asymptomatic. Medications include Toprol and Metformin. His resting heart rate is well controlled. What do you advise to decrease his risk for stroke?

A. No additional treatment is necessary.

B. Start ASA 325 mg daily.

C. Start ASA 81 mg daily and Plavix 75 mg daily.

D. Begin warfarin.

E. Jantoven, dabigatran or rivaroxaban should be started.

A 76 year old male with HTN and diabetes presents with the new diagnosis of atrial fibrillation, discovered on a preoperative EKG for cataract surgery. He is active and asymptomatic. Medications include Toprol and Metformin. His resting heart rate is well controlled. What do you advise to decrease his risk for stroke?

A. No additional treatment is necessary.

B. Start ASA 325 mg daily.

C. Start ASA 81 mg daily and Plavix 75 mg daily.

D. Begin warfarin.

E. Jantoven, dabigatran or rivaroxaban should be started.

18,113 patients randomized to twice daily dabigatran (110,150 mg) or warfarin.

Inclusion: over 75 years old and ≥1: Prior CVA or TIA EF <40%, h/o NYHA class II 65-74 years old with DM, HTN or ASCAD

1⁰ Endpoint: stroke or systemic embolization

Median follow-up = 2 years

History of heart valve disorder Need for anticoagulant treatment of

disorders other than atrial fibrillation Stroke in the previous 6 months Severe renal impairment (CrCl <30 cc/min) Reversible causes of atrial fibrillation

(cardiac surgery, untreated hyperthyroidism) Plan to perform pulmonary vein isolation

Increased bleeding risk:-major surgery <1 month or planned > 3 months-history of intracranial, intraocular, spinal or

retroperitoneal or atraumatic intra-articular bleeds-gastrointestinal hemorrhage <1 year; PUD < 1

month-hemorrhagic disorder-uncontrolled hypertension-malignancy or radiation therapy < 6 months;

survival < 3 years

Anemia (Hgb <10) or thrombocytopenia (<100)

Active endocarditis Active liver disease Pregnancy or not taking contraception

For patients with CrCl >30 mL/min: 150 mg orally, twice daily.

For patients with CrCl 15-30 mL/min: 75 mg orally, twice daily.

Missed doses should be skipped if it cannot be taken at least 6 hours before the next scheduled dose.

From warfarin: When converting patients from warfarin

therapy to PRADAXA, discontinue warfarin and start PRADAXA when the international normalized ratio (INR) is below 2.0

From Parenteral Therapy: start 0 to 2 hours before the time that the

next dose of the parenteral drug was to have been administered

Before initiating treatment with a parenteral anticoagulant:

Wait 12 hours for CrCl ≥30 mL/min

Wait 24 hours for CrCl <30 mL/min.

For CrCl >50 mL/min, start warfarin 3 days before discontinuing PRADAXA.

For CrCl 31-50 mL/min, start warfarin 2 days before discontinuing PRADAXA.

For CrCl 15-30 mL/min, start warfarin 1 day before discontinuing PRADAXA.

Discontinue PRADAXA 1 to 2 days (CrCl ≥50 mL/min) or 3 to 5 days (CrCl <50 mL/min) before invasive or surgical procedures.

Consider longer times for patients undergoing major surgery, spinal puncture, or placement of a spinal or epidural catheter.

Most common adverse reactions (>15%) are gastritis-like symptoms and bleeding.

P-gp inducers and inhibitors: avoid coadministration of rifampin.

Offering PRADAXA to all eligible new atrial fibrillation consultations

Prescribing PRADAXA to appropriate existing atrial fibrillation patients who request it

Screening existing atrial fibrillation patients and providing educational materials

limelightprsonar.files.wordpress.com

Wafarin

Dabigatran

Rivaroxaban

Apixaban

X

X

X

X X

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2

Prior TIA/CVA

Primary Outcome

Bleeding

Death

Notes

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2 2.1 3.5 2.1

Prior TIA/CVA 20% 55% 19%

Primary Outcome

Bleeding

Death

Notes

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2 2.1 3.5 2.1

Prior TIA/CVA 20% 55% 19%

Primary Outcome Superior (1.53%) Noninferior/Superior? (1.7-

2.1%)

Superior (1.27%)

Bleeding

Death

Notes

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2 2.1 3.5 2.1

Prior TIA/CVA 20% 55% 19%

Primary Outcome Superior (1.53%) Noninferior/Superior? (1.7-

2.1%)

Superior (1.27%)

Bleeding Noninferior (3.11%)

Noninferior (3.6%)

Superior (2.1%)

Death

Notes

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2 2.1 3.5 2.1

Prior TIA/CVA 20% 55% 19%

Primary Outcome Superior (1.53%) Noninferior/Superior? (1.7-

2.1%)

Superior (1.27%)

Bleeding Noninferior (3.11%)

Noninferior (3.6%)

Superior (2.1%)

Death Noninferior (p=0.051)

Noninferior Superior

Notes

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2 2.1 3.5 2.1

Prior TIA/CVA 20% 55% 19%

Primary Outcome Superior (1.53%) Noninferior/Superior? (1.7-

2.1%)

Superior (1.27%)

Bleeding Noninferior (3.11%)

Noninferior (3.6%)

Superior (2.1%)

Death Noninferior (p=0.051)

Noninferior Superior

Notes GIB? MI? ACS, DVT Not FDA Approved

Dabigatran Rivaroxaban Apixaban

Pharmacology 12-17 hrs (bid) 7-11 hrs (daily) 12 hrs (bid)

CHADS2 2.1 3.5 2.1

Prior TIA/CVA 20% 55% 19%

Primary Outcome Superior (1.53%) Noninferior/Superior? (1.7-

2.1%)

Superior (1.27%)

Bleeding Noninferior (3.11%)

Noninferior (3.6%)

Superior (2.1%)

Death Noninferior (p=0.051)

Noninferior Superior

Notes GIB? MI? ACS, DVT Not FDA Approved

I’m not dead yet!

Bring out your dead-

45% of patients with atrial fibrillation appropriately anticoagulated.

Broad indications for use. Safety with renal dysfunction. $$$$$$$

Strict rate control is not necessary in well compensated atrial fibrillation (III).

Dronedarone is an option to decrease cardiovascular hospitalizations in patients with paroxysmal atrial fibrillation (IIa). Not with class IV CHF or recent decompensation (III).

Evidence is mounting for catheter ablation (I). Dual anti-platelet therapy is an option in

patients unsuitable to safely sustain AC or due to patient preference (IIb).

Oral alternatives to warfarin are available (I).