Download Atrial Fibrillation

Joey Stafford
PGY - 2
• Epidemiology
• Pharmacologic management
•
•
•
•
•
Rate vs Rhythm Control
Rate Controlling Drugs
Antiarrhythmic Drugs
Anticoagulation to Prevent Emboli
Review of New Anticoagulants
• Special Considerations
• Review of worldwide population-based studies estimated that
the number of individuals with AF in 2010 was 33.5 million and
that there are about 5 million new cases each year.
• In 2010, the prevalence rates (per 100,000 population) were
noted to be 596 and 373 in men and women, respectively
• Incidence rates (per 100,000 person-years) were 78 and 60 in
men and women, respectively
• Rate Control
• Rhythm Control
• Prevention of
Thromboembolic Events
• AFFIRM Trial – Among patients with non-valvular atrial fibrillation, rate and
rhythm control strategies have equivalent impact on survival.
• RACE II Trial – In patients with permanent atrial fibrillation, lenient rate
control (HR < 110) is as effective as strict rate control (HR < 80) in
preventing cardiovascular events.
Thus, for asymptomatic patients with permanent AF, a more lenient rate control goal of
<110 beats/min may be reasonable
• In regards to HF patient’s with Atrial Fibrillation
• AF-CHF Trial – Assessed 1376 patients with a left ventricular EF <35%, HF symptoms,
and a history of paroxysmal or persistent AF
• Assigned to a strategy of either rhythm or rate control.
• There was no significant difference in the primary outcome of death from
cardiovascular causes between the rhythm- and rate-control.
• Quality of life and functional capacity were similar in both treatment groups
• Importance of Rate Control
• Maintenance of hemodynamic stability
• Prevention of tachycardia-mediated cardiomyopathy
• Utilization of medications that slow AV nodal conduction
•
•
•
•
Beta Blockers
Calcium Channel Blockers (Diltiazem or Verapamil)
Digoxin
Amiodarone*
• RACE II Trial
• lenient control was non-inferior to strict rate control
• There were nearly nine times as many visits (684 versus 75) to achieve rate the
control target(s) in those assigned to strict control
• Important effects of Beta Blockers to Consider
• Atenolol, Metoprolol, Timolol, pindolol, nadolol have most supportive
evidence
• Bisoprolol and coreg can be used as well
• Important effects of Beta Blockers to Consider
•
•
•
•
•
•
Worsening heart failure
Hypotension
Bronchospasm
Reduced exercise tolerance
High-degree AV block
Bradycardia
• Specifically, nondihydropyridine CCBs
• Verapamil
• Initial dose typically 40 mg TID or QID, titrated up to a maximum dose
of 360 mg/d
• Diltiazem
• Started at 30 mg QID to a maxium dose of 360-480 mg/d; To
convert to sustained form, use the same total daily dose
• Important effects of CCBs to Consider
• Negative inotropic effect; Avoid in patients with NYHA Class III or IV
• Verapamil and Digoxin interact -> digoxin levels may increase
• Digoxin
• Typically used if beta blockers or CCBs have not been effective. Was
previously used as 1st line in Afib patients with LV dysfunction
• Beta Blockers now standard of therapy in this group
• TREAT-AF study showed increased mortality in those with and without HF.
• Amiodarone
• 2014 AHA/ACC guideline recommend as second-line therapy for chronic
rate control when other therapies are contraindicated or unsuccessful
• Also used to maintain sinus rhythm
• Many antiarrhythmic drug therapies started as an inpatient to
monitor EKG changes.
Flecainide, propafenone, amiodarone and dronedarone may be initiated as
an outpatient.
• Flecainide and Propafenone
• “Pill in the Pocket” Approach
• Do not use in patient’s with structural heart disease, LV dysfunction, AV
nodal dysfunction, long QT, bradycardia or CAD -> Do not use after MI
• Will need short-acting beta blocker on Non-DHP calcium channel blocker
30 minutes before therapy.
• 1st dose should be monitored.
• Amiodarone and Dronedarone
• Only two drugs that can be initiated as an outpatient in patients in Afib
• Preferred agent in patients
with HF or LVH
• Monitor thyroid, liver and
pulmonary funciton
• Can prolong QT but has not
been shown to cuase
Torsades
• NYHA Class III or IV HF or
those with an EF < 35%
should not receive
dronedarone
• PALLAS Study
• May lead to increase in
measured serum creatinine
due to inhibition of tubular
secretion; does not affect
GFR
• Ideal alternative to
Amiodarone in patients with
CAD and no LV dysfunction.
• Embolization of atrial thrombi can occur with any form atrial
fibrillation. Thrombus commonly forms in LA appendage.
• Of note, The AFFIRM and RACE trials demonstrated that embolic
events occurred with equal frequency regardless of whether a
rate control or rhythm-control strategy was pursued
• Aspirin recommended for low-risk patients
• ACTIVE A Trial – Compared to ASA alone, ASA + Plavix
reduces major vascular events but increased the risk of major
bleeding.
• ACTIVE W Trial – ASA + Plavix was inferior to warfarin for
prevention of stroke, systemic embolism, MI and CV death but
carried similar bleeding risk.
• Vitamin K Antagonist
• ATRIA Study – 13,559 patients with nonvalvular Afib. Net
clinical benefit significant at CHADS2 score of 2+.
• Considerations for use of Coumadin
•
•
•
•
Comfort with periodic INR checks
Cost of newer anticoagulants
Patient’s with CKD and GFR < 30
Contraindications to use of newer agents
• Oral Direct Thrombin Inhibitor
• RE-LY Trial
• Compared Pradaxa to adjusted dose of Warfarin
• Pradaxa 110 mg twice daily dosing was non-inferior to Coumadin in
preventing outcome of stroke or systemic embolims
• Pradaxa 150 mg twice daily dosing was significantly more superior to
Warfarins.
• Superior to Warfarin in preventing thromboembolic events with redueced
life-threatening bleeding; however, higher risk of GI bleeding was noted.
• Pradaxa 150 mg PO BID recommended for patients not at high risk
for bleeding and who have adequate renal function
• Pradaxa 75 mg PO BID may be used if CrCl 15-30 mL/min but has not been
tested in clinical trials
• Oral Direct Factor Xa Inhibitor
• ROCKET-AF
• Among, patients with intermediate to high risk non-valvular afib, Xarelto
was non-inferior warfarin in preventing stroke and thromboembolism.
• No difference in major bleeding but demonstrated reduction in
intracranial bleeding.
• Patient’s received 20 mg PO Daily, or 15 mg if CrCl between 30-49
• Oral Direct Factor Xa Inhibitor
• ARISTOTLE
• Evaluated patients with intermediate risk non-valvular atrial fibrillation.
• Apixaban showed greater reduction in rates of stroke or systemic
embolism.
• Lower rates of major bleeding
• Dosed 5 mg PO BID or 2.5 mg PO BID with the following risk
factors:
• Age >= 80
• Weight <= 60
• Serum Cr >= 1.5
• Oral Direct Factor Xa Inhibitor
• ENGAGE-AF-TIMI 48
• Evaluated 21,105 patients with moderate to high risk nonvalvular AF
• Approved in Japan; Recently approved for use in the US
• AHA/ACC/HRS AF Guidelines
• In patient’s with nonvalvular AF with CHADS-VASc score greater than or
equal to 2, recommend oral anticoagulation with:
• Warfarin, goal INR 2-3 (Class IA)
• Dabigatrin (Class 1B)
• Rivaroxaban (Class 1B)
• Apixaban (Class 1B)
• HAS-BLED
Hypertension
Abnormal renal or liver
function
Stroke
Bleeding
Labile INRs
Elderly (age > 65)
Drug (ASA, NSAIDS) or alcohol
use
Score > 2 indicates “high risk”
Score
0
1
2
3
4
5
Bleeding Rate %/Yr
1.13
1.02
1.88
3.74
8.7
12.5
No available date for scores greater
than 5
• Warfarin the treatment of choice
• Dabigatran, Rivaroxaban and Apixaban should not be considered
alternatives to Coumadin
• Patients with Mechanical Mitral Valve should receive Warfarin
indefinitely with goal INR between 2.5 – 3.5