Rivaroxaban or Aspirin for Extended Treatment of Venous Thr - PowerPoint Presentation

Slide1

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism(EINSTEIN CHOICE)

Ryan Sparks,

PharmD

, BCPS

PGY2 Cardiology Resident

WakeMed

Health &

Hosptials

Raleigh, NCSlide2

Dr. Ryan Sparks (presenter)

Current PGY2 Cardiology Resident at

WakeMed

Health & Hospitals in Raleigh, North Carolina. He completed the doctor of pharmacy program at the UNC

Eshelman

School of Pharmacy in 2015. After completing residency, he will be taking a position at New Hanover Regional Medical Center in Wilmington, North CarolinaSlide3

Dr. Paul Dobesh (Mentor)

Dr.

Dobesh

received his Bachelor of Science in Pharmacy and his

PharmD

Degree from South Dakota State University in Brookings, SD. He completed an Internal Medicine Specialty Residency at the University of Texas at Austin at Brackenridge Hospital in Austin, TX. He is currently

as Associate

Professor of Pharmacy Practice with the University of Nebraska Medical Center in Omaha, NE. 

He lectures in the area of ischemic heart disease, antithrombotic therapy, and other cardiology and critical care topics. He has conducted research on antiplatelet and antithrombotic therapy, focusing on real-world utilization and health economics. Dr.

Dobesh

has published book chapters and several manuscripts in this area. Slide4

Disclosure Statement

I have no financial relationships with commercial interests that pertain to the content presented in this program.Slide5

BackgroundCumulative incidence of VTE is ~11% within 1 year after stopping VKA

VTE has associated long term sequelae

P

ost-thrombotic syndrome

C

hronic thromboembolic pulmonary hypertension

Recurrent VTE

Guidelines support long-term anticoagulation

Haematologica

2007; 92:199-205

Chest 2016; 149:315-352Slide6

BackgroundWarfarin is effective for prevention of recurrent VTE but has significant limitations

INR monitoring

Drug and food interactions

Variability in response

Lower intensity warfarin strategies are less effective and do not decrease bleeding risk

Kearon,

et al

. (ELATE): Increase in VTE recurrence with similar bleeding rates when lower INR target was utilized

N

Engl

J Med

2003; 348:1425-34

N

Engl

J Med

2003; 349:631-639Slide7

BackgroundEINSTEIN-EXTENSION

Double blind, placebo controlled, RCT

1197 patients who had completed treatment for confirmed symptomatic VTE

Rivaroxaban 20 mg PO daily vs placebo

Significant reduction in recurrent VTE with rivaroxaban

No difference in major bleeding

events

AMPLIFY-EXTENSION

Double blind, placebo controlled, RCT

2482 patients who had completed treatment for confirmed symptomatic VTE

Apixaban

2.5 mg PO BID vs

apixaban

5 mg PO BID vs placebo

Significant reduction in recurrent VTE or death with both

apixaban

arms

No difference in major bleeding

events

N

Engl

J Med

2013; 368:699-708

N

Engl

J Med

2010; 363:2499-510Slide8

BackgroundASPIRE

Double blind, placebo controlled RCT

822 patients who had completed treatment for first unprovoked VTE

ASA 100 mg/d vs placebo

C

omposite

of VTE, MI, stroke, CV

death: 8.0% with

placebo vs 5.2

% with aspirin (p=0.01)

WARFASA

Double blind, placebo controlled RCT

403

patients who had completed treatment for first unprovoked VTE

ASA 100 mg/d vs

placebo

Recurrent VTE occurred in 6.6% of aspirin and 11.2% of placebo patients per year (p=0.02)

N

Engl

J Med

2012; 367; 1979-87

N

Engl

J Med

2012; 366:1959-67Slide9

EINSTEIN CHOICE - ObjectiveTo compare the safety and efficacy of rivaroxaban to aspirin in patients with venous thromboembolism who had completed 6 to 12 months of therapy and for whom there was clinical uncertainty over the need for continued anticoagulationSlide10

MethodsSlide11

Methods

Inclusion

18 years of age or older

Confirmed symptomatic proximal DVT or PE

T

reated for 6 to 12 months with anticoagulant

Had not interrupted anticoagulant therapy for more than 7 days before randomization

Exclusion

Contraindication to anticoagulant therapy

Requirement of extended anticoagulant or antiplatelet therapy

CrCl

less than 30 ml/min

Hepatic disease with associated coagulopathy

Concomitant strong CYP3A4 and P-

gp

inhibitor/inducers

Life expectancy less than 6 months

Child bearing potential without proper contraception, pregnancy or breast feeding

Participation in another study within 30 days prior to randomizationSlide12

Efficacy OutcomesSlide13

Safety OutcomesSlide14

Statistical Analysis80 primary efficacy outcomes needed

to

provide 90% power for superiority

Needed to enroll 3300 patients to provide power

Analysis included all patients who received at least one dose of study medicationSlide15

Baseline DemographicsSlide16

Primary Efficacy Results

P

-value < 0.001 for rivaroxaban 20 mg vs aspirin

P-value < 0.001 for rivaroxaban 10 mg vs aspirin

P-value = 0.42 for rivaroxaban 20 mg vs rivaroxaban 10 mg comparisonSlide17

Efficacy Results

Outcomes

Rivaroxaban 20 mg PO daily (n=1107)

Rivaroxaban 10 mg PO daily (n=1127)

Aspirin 100 mg (n=1131)

p-value

20 mg vs ASA

p-value

10 mg vs ASA

Primary - Recurrent VTE, n (%)

17

(1.5

)

13

(1.2

)

50

(4.4

)

<0.001

<0.001

Deep

vein thrombosis

,

n (%)

9 (0.8)

7 (0.6)

29 (2.6)

--

--

Pulmonary embolism,

n (%)

6 (0.5)

5 (0.4)

19 (1.7)

--

--

Fatal VTE, n (%)

2

(0.2

)

0

(0)

2

(0.2)

--

--

MI, ischemic stroke, systemic embolism;

n (%)

3 (0.3)

5 (0.4)

7 (0.6%)

--

--Slide18

Safety Results

Outcomes

Rivaroxaban 20 mg PO daily (n=1107)

Rivaroxaban 10 mg PO daily (n=1127)

Aspirin 100 mg (n=1131)

p-value

20 mg vs ASA

p-value

10 mg vs ASA

Major bleeding, n (%)

6

(0.5

)

5 (0.4)

3 (0.3)

0.32

0.50

Clinically relevant nonmajor bleeding, n (%)

30

(2.7)

22 (2.0)

20

(1.8)

0.14

0.78

Non-major

bleeding associated with study drug interruption for more than 14 days, n (%)

17 (1.5)

12 (1.1)

12 (1.1)

0.33

0.96Slide19

Author’s ConclusionsRivaroxaban was more effective than aspirin for prevention of recurrent VTE without increased bleeding risk in patients with VTE in equipoise for continued anticoagulation

With either 20 mg or 10 mg rivaroxaban dosing

Benefit was demonstrated in patients with provoked and non-provoked VTESlide20

CritiqueStrengths

Large randomized controlled trial

Tested full dose and prophylactic dose rivaroxaban

Active control – aspirin

Inclusion of patients with weight > 90 kg

Weaknesses

Excluded patients who required long term anticoagulation

Not powered to detect difference between rivaroxaban doses

Limited data for patients with renal dysfunctionSlide21

ConclusionsAspirin is inferior to rivaroxaban for the prevention of recurrent VTE

Rivaroxaban 10 mg PO daily may be considered for secondary prevention in patients who do not require extended anticoagulation

Full dose anticoagulation should still be utilized in patients who require anticoagulation

Risk of low dose rivaroxaban strategy is still unknown for many patientsSlide22

Practice ImplicationsRivaroxaban should be used preferentially over aspirin for recurrent VTE prevention

Anticoagulation clinics and services will

need to modify practice to accommodate

new strategies

No direct DOAC

comparisons

Long term safety of extended rivaroxaban remains unclear

More patients may receive extended DOAC therapySlide23

AcknowledgementsPaul Dobesh

,

PharmD

, FCCP, BCPS-AQ Cardiology

J. Erin (

Allender

) Ledford,

PharmD

, BCPS-AQ Cardiology, BCCCP

Janna Beavers,

PharmD

, BCPSSlide24

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism(EINSTEIN CHOICE)

Ryan Sparks,

PharmD

, BCPS

PGY2 Cardiology Resident

WakeMed

Health &

Hosptials

Raleigh, NCSlide25

AnnouncementsPlease join us June 27th as Dr. Taylor Church (Vanderbilt) presents the

Ticagrelor

versus

Clopidogrel

in Symptomatic Peripheral Artery

Disease

(EUCLID

)

trial. Her mentor will be Dr. Kelly Rogers (University of Tennessee).