Atrial Fibrillation: Changing Indications and New Medications - - PowerPoint PPT Presentation

▶
atrial fibrillation changing indications and new
SMART_READER_LITE
LIVE PREVIEW

Atrial Fibrillation: Changing Indications and New Medications - - PowerPoint PPT Presentation

Jul 19, 2023 147 likes •743 views

Atrial Fibrillation: Changing Indications and New Medications Jessica Evert MD UCSF Department of Family and Community Medicine Special Thanks and Recognition: Edward Kersh, MD, FACC Chief of Cardiology, St. Luke s Hospital, SF Clinical

slide-1
SLIDE 1

Atrial Fibrillation: Changing Indications and New Medications

Jessica Evert MD UCSF Department of Family and Community Medicine

Special Thanks and Recognition: Edward Kersh, MD, FACC Chief of Cardiology, St. Luke’s Hospital, SF Clinical Professor of Medicine, UCSF Sutter Pacific Medical Foundation

slide-2
SLIDE 2

Terminology: No longer paroxysmal /chronic

 Lone (no heart disease)  Paroxysmal (lasts less than 7 days; self terminating)  Persistent (more than 7 day; requires intervention to terminate)  Long-standing persistent (last more than 12 months)  Permanent (pt or physician decide not to seek restoration/maintenance of NSR)  NVAF (non-valvular AFib)

slide-3
SLIDE 3

WHY?

AF Increases Stroke Risk by Nearly 500%

Wolf et al. Stroke. 1991;22:983-988.

Risk ratio = 4.8

P < 0.001

slide-4
SLIDE 4

The annual risk of Stroke with AFIb is 8% on average. 8% of 5,000,000 = 400,000 strokes per year.

slide-5
SLIDE 5

Fuster, V. et al. J Am Coll Cardiol 2011;57:e101-e198

Incidence of AF Increases with Age

15% of octogenarians will have A fib

slide-6
SLIDE 6

Fuster, V. et al. J Am Coll Cardiol 2011;57:e101-e198

Stroke rates in relation to age in untreated control groups of randomized trials

Risk of Stroke in AF Increases with Age

8%

slide-7
SLIDE 7

Severe Disability Is Increased in Patients With Stroke Due to AF

3x incidence of being bedridden with AFib Lin et al. Stroke. 1996;27:1760-1764.

slide-8
SLIDE 8

The aggregate RRR for all stroke was 62% (95% CI, 48%–72%)

Adapted from Hart. Ann Intern Med. 1999;131:492; with permission.

100% 50%

  • 100%

EAFT (n=439) CAFA (n=378) AFASAK (n=671)

Warfarin Better Warfarin Worse

SPAF (n=421) BAATAF (n=420) SPINAF (n=571) All 6 Trials (n=2900)

WHY?

Oral Anticoagulation Reduces Stroke in AF (8% to 3%)

  • 50%

RRR=relative risk reduction

Warfarin Compared With Placebo

slide-9
SLIDE 9

WARFARIN

SPAF, Circulation 1991 3%

slide-10
SLIDE 10

History of Anticoagulation

(70 years of warfarin)

  • 1933 - a farmer shows up at the U. of Wisconsin School of Agriculture with a milk can full
  • f blood which would not coagulate. In his truck, he had also brought a dead heifer and some

spoiled clover hay. He wanted to know what had killed his cow.

  • 1939 – Dr. Paul Link isolates dicumerol
  • 1941 - Patented by WARF
  • 1950 – Marketed as rat poison
  • 1951 – unsuccessful overdose treated with Vitamin K
  • 1954 – FDA approves use in humans
  • 1983 – INR introduced
  • 1991 – Framingham demonstrates role of Afib in Stroke
  • 1991 – Generic warfarin (FDA requires absorption to be within 80–125%)
  • 1999 – Risk reduction with anticoagulants demonstrated
  • 2005 – Sportif Trial - ximelagratan
  • 2011 – New agents introduced
slide-11
SLIDE 11

WHO?

Rate control and anticoagulate everyone initally

slide-12
SLIDE 12

Who? :

Clinical predictors of stroke in AFIB

 Prior TIA or CVA  Prosthetic Valve  RHD  Hypertension  LV dysfunction/CHF  Age > 75  Cardiomyopathies (restrictive or hypertrophic)  Diabetes  CAD  Thyrotoxicosis

slide-13
SLIDE 13

Who? :

Echo Predictors of Stroke in Afib

  • LV Dysfunction
  • Mitral Valve Disease, Annular Calcium
  • LA Enlargement
  • Spontaneous Echo Contrast (Smoke)
  • LAA emptying velocity
  • LA thrombus
  • Absence of mitral regurgitation
slide-14
SLIDE 14

Thrombus Forms in the Left Atrium

(rarely seen on TTE)

slide-15
SLIDE 15

LAA Clot

slide-16
SLIDE 16

LAA Clot by TEE in appendage

slide-17
SLIDE 17

I IIa IIb III

Classes of Recommendations

Intervention is useful and effective Evidence conflicts/opinions differ but lean toward efficacy Evidence conflicts/opinions differ but lean against efficacy Intervention is not useful/effective and may be harmful

Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf.

slide-18
SLIDE 18

Class I

Benefit >>> R >>> Risk Procedure/ Treatment SHOULD be performed/ administered

Class IIa

Benefit >> R Risk sk Addit itio ional s studies ies w wit ith focuse sed objectives n s needed IT IS REASONABLE to perform procedure/administer treatment

Class IIb

Benefit ≥ Risk Addit itio ional s studies ies w wit ith broad objectives n s needed; Additional r registry data would be be he helpful Procedure/Treatment MAY BE CONSIDERED

Class III

Risk ≥ Benefit No addit itio ional s studies ies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain

  • r not well established

is not recommended is not indicated should not is not useful/effective/beneficial may be harmful

Applying Classification of Recommendations

slide-19
SLIDE 19

Weighing the Evidence

Weight of evidence grades:

= Data from many large, randomized trials = Data from fewer, smaller randomized trials, careful analyses of nonrandomized studies,

  • bservational registries

= Expert consensus

Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf.

slide-20
SLIDE 20
slide-21
SLIDE 21
slide-22
SLIDE 22

ACC/AHA Guidelines 2014: Determine the Risk

slide-23
SLIDE 23

ACC/AHA Guidelines 2014: Determine the Risk

Oral Anticoagulation for score >/= 2 0 = no anticoagulation 1= options

Hypertropic Cardiomyopathy= Ignore Score (and anticoagulate)

slide-24
SLIDE 24

What to do with 1?

  • No Anticoagulation
  • Oral Anticoagulation
  • Aspirin (IIb)
slide-25
SLIDE 25

What?

  • Parenteral Agents – heparin, enoxaparin, Arixtra
  • Antiplatelet Agents
  • Aspirin
  • clopidigrel
  • Vitamin K antagonists- Coumadin
  • Direct Thrombin Inhibitors
  • Dabigatran
  • Factor XA inhibitors
  • Apixaban
  • Rivaroxaban
  • Appendectomy
slide-26
SLIDE 26

Newer Oral AntiCoagulants (NOACs)

  • Dabigatran (Pradaxa)
  • Rivaroxaban (Xarelto)
  • Apixaban (Eliquis)
  • Edoxaban (Savaysa, Lixiana)

Contraindicated in patients with mechanical heart values or hemodynamically significant mitral stenosis Do not use in ESRD; reduce dose in mod/sev CKD

slide-27
SLIDE 27
slide-28
SLIDE 28

Fuster, V. et al. J Am Coll Cardiol 2011;57:e101-e198

The problem with warfarin: The Therapeutic Window Stroke vs intracranial bleeding in relation to intensity of anticoagulation

Therapeutic window

slide-29
SLIDE 29

Connolly SJ et al. Circ. 2008,118:2029-2037

slide-30
SLIDE 30

Emergency Hospitalizations for Adverse Drug Events in Older U.S. Adults

Budnitz DS et al. N Engl J Med 2011;365:2002-2012.

slide-31
SLIDE 31

Fuster, V. et al. J Am Coll Cardiol 2011;57:e101-e198

What About Aspirin?

slide-32
SLIDE 32

Aspirin – half as effective

SPAF, Circulation 1991

slide-33
SLIDE 33

ASA + PLAVIX – less stroke, more bleeding

n = 7554 pts unsuitable for warfarin

The ACTIVE Investigators. N Engl J Med 2009;360:2066-2078

Stroke, MI, Embolism, death

Risk of stroke decreased 28%

slide-34
SLIDE 34

Red vs White Thrombus

  • Dominated by RBC’s
  • Low Pressure systems (veins,

LA)

  • Rx anti-thrombin agents
  • Stasis (DVT, AFib)
  • Dominated by platelets
  • High-pressure systems (arteries,

bypass)

  • Rx antiplatlet agents (ASA,

Plavix)

  • Plaque Rupture (ACS)

White thrombus

Red Thrombus

slide-35
SLIDE 35

New Agents

  • Direct Thrombin Inhibitor

–Dabigatran

  • Factor Xa Inhibitor

–Rivaroxiban –Apixaban –Edoxaban

slide-36
SLIDE 36
slide-37
SLIDE 37

RELY - RESULTS

Connolly SJ et al. N Engl J Med 2009;361:1139-1151

35% reduction in stroke and emboli with D 150

slide-38
SLIDE 38

Rivaroxiban: Rocket AF Trial

Patel MR et al. N Engl J Med 2011. DOI: 10.1056/NEJMoa1009638

21% reduction in stroke and emboli

slide-39
SLIDE 39

Rocket AF - Primary End Point of Stroke or Systemic Embolism.

Patel MR et al. N Engl J Med 2011. DOI: 10.1056/NEJMoa1009638

slide-40
SLIDE 40

ARISTOTLE – Apixaban vs Warfarin

n = 18000

Granger CB et al. N Engl J Med 2011. DOI: 1056

24% reduction in stroke and emboli 31% reduction in major bleeding

slide-41
SLIDE 41

Granger CB et al. N Engl J Med 2011. DOI: 1056

Aristotle – Apixaban vs Warfarin

n=18000

slide-42
SLIDE 42

Edoxaban: Engage AF – Timi48

Giugliano RP et al. N Engl J Med 2013;369:2093-2104

13% stroke reduction 20% bleeding reduction

slide-43
SLIDE 43

COMPARISON

Drug Trial

(chads2)

Dose TTR %

Stroke Reduction %

ICH %/yr

RR Mortality (p value) Major Bleed

Dabig DTI

RELY (2.1)

150 bid 64 35% 0.10 .88 (0.051) 7% Rivaro Xa

Rocket AF (3.5)

20 qd 55 21% 0.50 .92 (0.15) 6% Apixa Xa

Aristotle (2.1)

5 bid 62 24% 0.24 .89 (0.047) 31% Edoxa Xa

Engage AF

60 qd 68 13% 0.50 .86 (.003) 20%

slide-44
SLIDE 44

Efficacy (stroke) vs Side Effect (bleeding)

slide-45
SLIDE 45

Treating Bleeding

  • Wait – short half life compared to warfarin
  • Maintain renal perfusion

– PRBC – Fluids – Diuretic (?)

  • Drive Thrombin production

– FFP (?) – Vitamin K (?) – Prothrombin Complex Concentrates

  • Dialysis
  • Antibody – Praxbind
  • Dummy factor Xa – in development
slide-46
SLIDE 46
slide-47
SLIDE 47

DTI and Xa Summary Points

  • Onset of action in 2 hours
  • No need to bridge with heparin (shorter LOS)
  • Less time off therapy
  • No dose titration/no INR’s
  • Superior or non-inferior to warfarin
  • Fewer drug interactions
  • Less ICH
slide-48
SLIDE 48

Dosing the NOACs

Dabigatran (Pradaxa) CrCl>30 = 150 mg BID CrCl 15-30 = 75mg BID Rivaroxaban (Xarelto) CrCl > 50 = 20 mg Qday Crcl 15-50 = 15 mg Qday Aphixaban (Eliquis) –liver metabolized, only one you can use in ESRD 5mg BID 2.5 mg BID (if has 2 or more of following: age > 80, weight > 60 kg, Cr > 1.5 mg/dL) Endoxaban (Savaysa, Lixiana) CrCl > 95 = don’t use CrCl 51-95 = 60mg Qday CrCl 15-50 = 30 mg Qday

When CrCl < 15 or ESRD, Warfarin is recommended med

slide-49
SLIDE 49

Appendectomy

  • Surgical
  • Interventional

Maisel W. N Engl J Med 2009;360:2601-2603

slide-50
SLIDE 50

When and for how long ?

  • Anticoagulate and rate control everyone initially
  • Decide on cardioversion, ablation, or rate control
  • 4 weeks after cardioversion, decide on the need for long

term anticoagulation based on CHADS2-VASc Score

slide-51
SLIDE 51

AFFIRM: Rhythm-Control vs Rate-Control

5300 patients >65 0r < 65 + 1 risk factor with current or recent Afib (225 centers 1995-99)

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM). N Engl J Med 2002;347:1825-1833

slide-52
SLIDE 52

AFFIRM: On treatment Post-Hoc Analysis

Variable Sinus Rhythm Warfarin Digoxin AAD RR 0.54 (.42-.70) P<.0001 0.47 (.36-.61) P<.0001 1.50 (1.18-1.89 P <.0001 1.41 (1.10-1.83) P < .0001

slide-53
SLIDE 53
slide-54
SLIDE 54

Catheter Ablation Decision Model

slide-55
SLIDE 55

CARDIOVERSION ALGORITHM

slide-56
SLIDE 56

Summary

  • Why – Reduce the risk of Stroke
  • Who – Risk (bleeding) vs Benefit (stroke)
  • What – Warfarin may become thing of the past
  • When – At time of presentation if possible
  • For How Long ?

– CHADS-VASc > 2 – forever – CHADS-VASc < 2 – 1 month or aspirin forever – Don’t make promises

slide-57
SLIDE 57
slide-58
SLIDE 58

Thank you.