Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease

Thursday | July 23, 2020| 12:00pm - 1:00pm ESTPresenter:

Geoff Barnes, MD, MScGuest Speakers:Renato Lopes, MD

Dominick Angiolillo, MDRoxana Mehran, MD

Moderators:Tracy Minichiello, MD

Arthur Allen, PharmD, CACPDiane Wirth, ANP

PresentersGeoff Barnes, MD, MSc• Assistant Professor of Medicine, Vascular and

Cardiovascular Medicine, University of Michigan

Tracy Minichiello, MD• Professor of Medicine, University of California, San

Francisco• Chief of Anticoagulation and Thrombosis Services,

San Francisco VA Medical Center

Arthur Allen, PharmD, CACP• Anticoagulation Program Manager, VA Salt Lake City

Health Care System

Diane Wirth, ANP, CACP• Adult Nurse Practitioner, Grady Memorial Hospital• Interim Executive Director of Cardiovascular Services

and Manager of the Heart Failure Program, Grady Memorial Hospital

Renato Lopes, MD• Professor of Medicine of the Department of Medicine

of the Division of Cardiology at Duke University Medical Center, Duke Clinical Research Institute

Dominick Angiolillo, MD• Professor of Medicine with tenure status, University of

Florida Health System• Director of Cardiovascular Research, University of

Florida Health System• Program Director of the Interventional Cardiology

Fellowship Program, University of Florida Health System

• Staff cardiologist and interventional cardiologist, University of Florida Health System

Roxana Mehran, MD• Professor of Medicine, Zena and Michael A. Wiener

Cardiovascular Institute at Mount Sinai School of Medicine

• Director of Interventional Cardiovascular Research and Clinical Trials, Zena and Michael A. Wiener Cardiovascular Institute at Mount Sinai School of Medicine

Background• Use of dual antiplatelet therapy (DAPT) after percutaneous coronary

intervention (PCI) ↓ ischemic events• P2Y12 inhibitor (e.g., clopidogrel, prasugrel, ticagrelor)• Aspirin

• 5-7% of PCI patients have indication for anticoagulation• Atrial fibrillation, venous thromboembolism, mechanical valve

Triple Therapy More Bleeding

Circulation 2019;139:775-786

Danish nationwide cohort study

Incidence of major bleeding• Number of antithrombotic meds• Comorbidities

Strategies to Reduce Bleeding• 4 RCTs in post-PCI period

• DOAC > warfarin• Shorter duration triple therapy• Dual-therapy right away?

• Reduce bleeding without increasing thrombotic risk

JAMA Cardiology 2019 doi: 10.1001/jamacardio.2019.1880

Current Guidelines• 2019 ACC/AHA/HRS Atrial

Fibrillation• If triple therapy choose

clopidogrel (Class IIa)• If PCI + AF chose DOAC over

warfarin (Class IIa)• If triple therapy switch to

double therapy ASAP (Class IIb)

J Am Coll Cardiol. 2019 Jan 21. pii: S0735-1097(19)30209-8Eur Heart J 2018; 29:213-260

Buccheri S, Angiolillo DJ, Capodanno D. Therap AdvCardiovasc Dis 2019; 13:1753944719891688

Current Guidance: North America vs. Europe

Untested

OAC-ALONE Study

Circulation. 2019;139:604–616

Study Design:• Prospective• Multi-center• Open-label• Non-inferiority

Intended Enrollment: 2000Actual Enrollment: 696

OAC-ALONE StudyOAC Alone (n=344)

OAC + Apt (n=346)

Age 74.9 ± 0.4 75.2 ± 0.4Male 190 (55.2%) 185 (53.5%)BMI 24.3 ± 3.4 24.4 ± 3.4Hypertension 292 (84.9%) 301 (87.0%)Diabetes 152 (44.2%) 138 (39.9%)Smoker 27 (7.9%) 23 (6.7%)EF ≤40% 49 (15.2%) 60 (18.6%)Prior MI 129 (37.5%) 137 (39.6%)

OAC Alone (n=344)

OAC + Apt (n=346)

CHADS-VASc 4.6 ± 1.4 4.6 ± 1.4Number of prior stents

2 (1-3) 2 (1-3)

Drug-eluting 246 (71.7%) 240 (70.6%)Bare metal 97 (28.3%) 100 (29.4%)Left Main 23 (6.7%) 22 (6.4%)Multi-vessel 119 (34.6%) 119 (35.0%)Years since PCI 4.4 (1.8-7.7) 4.6 (2.4-7.4)

Circulation. 2019;139:604–616

OAC-ALONE Study• Warfarin – ~75% of population• DOAC – ~25% of population

• Antiplatelet regimen• Aspirin 86% of population• Clopidogrel 14% of population

Circulation. 2019;139:604–616

OAC-ALONE StudyAll-cause Death, MI, Stroke, Systemic Embolism Ischemic + Major Bleeding Events

Circulation. 2019;139:604–616

AFIRE Study Design

International Journal of Cardiology 265 (2018) 108–112

Study Design:• Multi-center• Randomized• Open-label

AFIRE Study Design

• Rivaroxaban 15mg daily• 10mg daily if CrCl 15-49 ml/min• Based on PK-PD studies in

Japanese population & J-ROCKET-AF

• “Stable CAD” No stenting or CABG within 1 year

• Follow up planned for 24-45 months

• Single antiplatelet therapy options:

• Aspirin 81-100mg daily• Clopidogrel 50-75mg daily• Prasugrel 2.5-3.75mg daily

• 5-10mg daily is typical in US

International Journal of Cardiology 265 (2018) 108–112NEJM 2019;381:1103-1113

AFIRE Study Design• Primary Endpoint

• Stroke, Systemic Embolism, MI, Unstable Angina revascularization, all-cause death

• Primary Safety Endpoint• ISTH major bleeding

• Statistical Design• Non-inferiority study

NEJM 2019;381:1103-1113

AFIRE Results• 2240 Screened 2236 Randomized 1973 completed follow up

Rivaroxaban Only (n=1107)

Riva + APT (n=1108)

Age 74.3 ± 8.3 74.4 ± 8.2Male 875 (79.0%) 876 (79.1%)Diabetes 461 (41.6%) 466 (42.2%)Smoker 146 (13.2%) 146 (13.2%)Prior PCI 781 (70.6%) 783 (70.7%)-Drug eluting 500/781 (69.2%) 477/783 (66.2%)-Bare metal 171/781 (23.7%) 171/783 (23.7%)CrCl 30-49 ml/min 300/1052 (28.5%) 293/1039 (28.2%)

NEJM 2019;381:1103-1113

AFIRE Results

NEJM 2019;381:1103-1113

Stroke, Embolism, MI, UARevasc, All-cause Death ISTH Major Bleeding

AFIRE Results

NEJM 2019;381:1103-1113

Rivaroxaban Only (n=1107)

Riva + Apt (n=1108)

HR (95% CI)

Primary Efficacy 89 (4.14) 121 (5.75) 0.72 (0.55-0.95)

MI 13 (0.59) 8 (0.37) 1.60 (0.67-3.87)

UARevasc 13 (0.59) 18 (0.84) 0.71 (0.35-1.44)

CV Death 26 (1.17) 43 (1.99) 0.59 (0.36-0.96)

Primary Safety 35 (1.62) 58 (2.76) 0.59 (0.39-0.89)

Any Bleeding 146 (7.22) 238 (12.72) 0.58 (0.47-0.71)

AFIRE Conclusions• Rivaroxaban monotherapy non-inferior to riva + antiplatelet in AF +

stable CAD patients• Cardiovascular events• Death from any cause

• Rivaroxaban monotherapy superior to riva + antiplatelet• Major bleeding

Study Strengths• Important clinical question• Randomized methodology• Few patients lost screening randomization step• Large patient population• Robust outcome measures

Study Limitation• Rivaroxaban and prasugrel doses differ from US dosing

• Open-label design potential for reporting bias

• High “loss to follow up” (~12% of randomized population)

• Study terminated early potential for over-estimating efficacy

• Mechanism for lower ischemic events in rivaroxaban monotherapy group without pre-specified causal mechanism chance finding?

• No use of DAPT (or similar) score

Group Discussion• How should these two studies inform care of AF + CAD patients in North

America?• Different patients• Different medication doses• Early termination

• At what point does a CAD patient become “stable”?• How to integrate “CAD complexity” into decision-making?• How to choose between warfarin and DOAC for AF + CAD patients?• Who was NOT randomized? Who should NOT stop DAPT?• How to discuss findings with cardiology?• How might these findings apply to VTE patients?

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Our 2-day Boot Camp course will be broadcast virtually on September 25th & 26th. The cost is only $199 with 30-day extended access so registered attendees can view sessions at a later date or more than once and still earn 10.75 CME hours.

Gain access to this thorough curriculum with this unique opportunity for online learning.

Faculty: Arthur Allen, PharmD; Geoff Barnes, MD; Nathan Clark, PharmD; Scott Kaatz, DO & Diane Wirth, ANP

acforumbootcamp.org

Join us for our next Webinar on COVID-19 and VTE: Breaking Down the Connection

Tuesday | August 4, 2020 | 7:00 - 8:00 PM ETin collaboration with

Hear about the most up to date information on COVID-19 from the Director of Global Infectious Diseases from Mass General Hospital, Dr. Edward Ryan and from Dr. Scott Kaatz, our AC Forum Board President, who personally experienced COVID-19 and PE.

Register Here!

Guest Speakers• Scott Kaatz, DO• Edward Ryan, MDModerator:• Rachel Rosovsky, MD

Panelists:• Geoff Barnes, MD• Sam Berkman, MD• Allison Burnett, PharmD• Geno Merli, MD• Tracy Minichiello, MD

This webinar is brought to you, in part, by the support of the following companies: