Atrial Fibrillation

Question 1

Types of Atrial Fibrillation

Answer 1

• Acute AF: Lasting 7d; requires treatment (electrical or pharmaceutical) to revert
• Permanent AF

Question 2

AF: Treatment Goals

Answer 2

• Prevention of stroke & other thromboembolic events
• Control the ventricular rate during episodes of AF
• In select patients, restore NSR

Question 3

CHADS2 Score

Answer 3

• CHF +1
• HTN +1
• Age >75 +1
• DM +1
• CVA +2

Question 4

CHADS risk of stroke

Answer 4

• 0: 1.9%
• 1: 2.8%
• 2: 4%
• 3: 5.9%
• 4: 8.5%
• 5: 12.5%
• 6: 18.2%

Question 5

CHADS2-VAS

Answer 5

• CHF: +1
• HTN: +1
• Age >75: +2
• DM: +1
• Stroke, TIA, or VTE: +2
• Vascular Dz: +1
• Age 65-74: +1
• Sex F: +1

Question 6

Treatment based on CHADS

Answer 6

• 0: Low risk - no Tx
• 1: Mod. Risk - oral anticoagulant or combo of ASA+Plavix
• 2: High Risk: Oral antithrombotic therapy

Question 7

The Ideal Anticoagulant

Answer 7

• Efficacious: Prevents the VTE
• Safe: Low/no likelihood of bleeding; has an antidote
• Endorsed by providers & Patients: easy to prescribe; Easy to take; inexpensive
• Easy to keep in therapeutic range: Predictable pharmacokinetics and pharmacodynamics; wide therapeutic index

Question 8

Warfarin: Facts

Answer 8

• MOA: Vitamin K antagonist
• PK: t1/2 20-60hr; Peak: 72-96hr; bioavailability 100%; excretion 1% unchanged in urine
• Pro: the most efficacious treatment for stroke prevention; relatively inexpensive
• Con: Provider reluctance to prescribe; pt reluctance to take; potential for bleeding; narrow therapeutic index; monitoring; variable dosing; drug-drug interactions; drug-food interactions

Question 9

Dabigatran (Pradaxa): General

Answer 9

• MOA: direct thrombin inhibitor (Anti-IIa)
• PK: t1/2 (CrCl >80) 12-17hr, (CrCl 30: 150mg BID; CrCl 15-30: 75mg BID; CrCl <15: Contraindicated
• Interactions: P-glycoprotein inducers (Rifampin); P-gp inhibitors (amiodarone, verapamil)

Question 10

Dabigatran: Efficacy & Safety

Answer 10

• Dabigatran 150mg BID vs. Warfarin, with an INR goal of 2-3 (Achieved 64%)
• Efficacy: 34% reduction of CVA or VTE
• Safety: Lower risk of bleeding, hemorrhagic stroke, and mortality

Question 11

Dabigatran: Patient Education

Answer 11

• Storage: Do not open, cut, or crush caps; MUST stay in original package until time it is taken
• Missed doses: Take >=6hr before next dose; do NOT double up on doses; If totally miss dose, pt at higher risk for stroke

Question 12

Dabigatran: Before and after procedure

Answer 12

• Dental Procedure: safe to take
• If surgery: D/C 1-2d prior if CrCl >50; 3-5d if CrCl <50
• For major surgery, spinal catheter, port, or of complete hemostasis needed: need longer interval of drug free time; consult w/surgeon

Question 13

Dabigatran: Conversion to/from other meds

Answer 13

• Conversion to:
• From warfarin: D/C warfarin & start dabigatran when INR is 2.0
• From UF Heparin: Start 0-2hrs prior to next dose (or when IV is turned off)
• From LMWH Heparin: start at the next dose of lovenox
• Conversion from:
• Start the agent 12hr after last dose of dabigatran if CrCl >30; 24hr after is CrCl <30

Question 14

Rivaroxaban (Xarelto): General

Answer 14

• MOA: Direct factor Xa inhibitor
• PK: t1/2 5-9hr, 11-13 in elderly & CKD; Peak 2-4hr; Bioavailability 60-80%; Excretion 1/3 renal, 2/3 liver
• Dosing: 20mg qd w/food; 15mg qd if CrCl 30-49; 10mg qd for DVT prevention
• Interactions:
• CYP 3A4 & P-gp inhibitors (antifungals and protease inhibitors)
• CYP3A4 and P-gp inducers (rifampin, carbamazepine, phenytoin, St. John’s wort)

Question 15

Rivaroxaban: Efficacy & Safety

Answer 15

Rivaroxaban vs. Warfarin for INR 2-3

• Efficacy: 12% relative risk reduction in CVA and VTE
• Safety: significant reduction in ICH and bleeding resulting in death

Question 16

Apixaban (Eloquis): General

Answer 16

• MOA: Direct facotr Xa inhibitor
• PK: t1/2 12hr; Peak 3-4hr; Bio 50-66%; Excretion 25% renal 75% hepatic
• Dosing: 5mg BID; 2.5mg BID if 2+ of: age >79, body wt. 1.5
• Interactions: Same as Xarelto (CYP 3A4 inhibitors and inducers)

Question 17

Apixaban: Efficacy & Safety

Answer 17

• Apixaban vs. Warfarin
• Efficacy: 21% risk reduction in CVA or VTE
• Safety: 31% reduction in bleeding; 11% reduction in all-cause mortality; less GI bleeding

Question 18

Newer Anticoagulant: Advantages

Answer 18

• Efficacy: Lower risk of storke/VTE (esp. Pradaxa)
• Safety: Lower hemorrhagic stroke, ICH, less bleeding (esp. Xarelto)
• Convenience/Predictability: Rapid onset; shorter t1/2, predictable effects; fixed doses; no adjustments, no INR monitoring

Question 19

Who should NOT get new anticoagulants

Answer 19

• Prosthetic heart valves
• Hemodynamically significant valve disease
• Severe renal failure (crCl <15)
• Advanced liver disease (impaired clotting)
• Those who miss doses frequently

Question 20

Newer Anticoagulant: Disadvantages

Answer 20

• Cost
• No antidotes
• More dyspepsia
• Some like monitoring

Question 21

Newer anticoagulants: Mgmt. of bleeding

Answer 21

• Keep in mind: short t1/2
• Minor bleeds: temporarily d/c med
• Usual Tx for Major Bleeds: d/c agent; compression; IVFs; Blood products (FFP 2-4U, prothrombin complex concentrate, recombinant factor VIIa 90mcg/kg); oral charcoal MAY help
• If life threatening: Dabigatran is partially dialyzable; antidote for factor Xa-I is in phase 2

Question 22

When to use which agent: anticoagulants

Answer 22

• New patients: if they can affors, start new drug
• For those not managing well on warfarin, switch to new agent
• For those on Warfarin, “doing well”: if in therapeutic range stay; convert if can afford