How Much AF is Too Much AF?Do I Initiate Anticoagulation Based on AF Detected on Device Monitoring?

Kenneth W. Mahaffey, MD, FACCProfessor of Medicine, CardiologyFaculty Associate Director, DCRIDirector, DCRI MegaTrials & CECDuke Clinical Research InstituteDurham, NC

DisclosuresConsultant Fees/HonorariaAdolor; Amgen; AstraZeneca; Bayer HealthCare; Biotronik, Inc.; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo, Inc.; Eli Lilly; Elsevier; Exeter Group; Forest; Genentech; Gilead; GlaxoSmithKline; Haemonetics; Johnson and Johnson; Medtronic; Merck and Co., Inc.; Novartis; Orexigen Therapeutics; Ortho-McNeil; Pfizer Inc; sanofi-aventis U.S. Inc.; Sun Pharma; Springer Publishing; WebMD Research/Research GrantsAbbott Vascular; Amgen; Amylin; AstraZeneca; Baxter; Bayer HealthCare; Boehringer Ingelheim; Bristol-Myers Squibb; Cordis; Daiichi Sankyo, Inc.; Edwards Lifesciences; Eli Lilly; GlaxoSmithKline; Guidant; Ikaria; INC Research; Johnson and Johnson; Kai Pharmaceuticals; Luitpold; Merck and Co., Inc.; Portola Pharmaceuticals; Pozen; Regado Biosciences; Roche; sanofi-aventis U.S. Inc.; Schering Plough; The Medicines Company

Screening for AF:Key Issues

• Predicting AF• Screening• Finding• Quantifying• Determining risk• Treating• Modifying outcomes

ASSERT TrialStroke or Systemic Embolism

Healy JS, et al. N Engl J Med. 2012;366:120-129.

Device-Detected Atrial TachyarrhythmiaDetected 0-3 months

No Asymptomatic Atrial TachycardiaDetected 0-3 months

HR = 2.4995% CI, 1.28-4.85P = 0.007

# at Risk Year 0.5 1.0 1.5 2.0 2.5+ 261 249 238 218 178 122- 2,319 2,145 2,070 1,922 1,5561,197

Years of Follow-upT0 at 3-month visit

Cum

ula

tive H

aza

rd R

ate

s

0 0.5 1.0 1.5 2.0 2.5

0.0

0.02

0.04

0.06

0.08

0.10

TRENDS TrialAF Burden & Thromboembolic Events

Annualized Rate

(Stroke & TIA)

Annualized Rate

(Stroke only)

Zero burden 1.1% 0.5%

Low burden < 5.5

hours1.1% 1.1%

High burden ≥ 5.5

hours2.4% 1.8%

Glotzer TV, et al. Circ Arrhythm Electrophysiol. 2009;474-480.

IMPACT TrialDevice Monitoring Guided Anticoagulation

Ip J, et al. Am Heart J. 2009;158:364-370.

• Patient Population:─ N = 2,718─ Dual-chamber ICD or

CRT-D device

─ CHADS2 ≥ 1

• Primary endpoint = composite of stroke, systemic embolism and major bleeding

• Hypothesis:─ Initiation and withdrawal

of anticoagulant therapy guided by ambulatory monitoring will improve clinical outcomes

• Phase A (N = 227) completed 2009

• Phase B ongoing

6m 12m 18m 24m 30m 36m

Randomize1:1

Group 2 (Control)

Group 1 (Intervention)

Conventional follow-up + physician-directed anticoagulation

Conventional follow-up + HM-guided anticoagulation

Summary

• Type of AF or AF burden should not influence stroke prevention treatment strategy

• Antithrombotic therapy for patients with AF should be guided by risk stratification based on validated prediction tools

• Patients with history of AF in sinus rhythm are not necessarily low risk