Rivaroxaban Real-world

Evidence: Validating safety

and effectiveness in clinical
practice
Learning Objectives

AF & Stroke Risk :

 Disease & Risk Assessment
 Patient Screening
 Treatment Protocol

New Oral Anti-Coagulant (NOAC) :

 Therapeutic Option Evaluation
 Most clinically use NOAC
 Understanding of Rivaroxaban and Usage
STROKE PREVENTION IN
ATRIAL FIBRILLATION
Atrial Fibrillation and Stroke Risk
 GLOBAL ATRIAL FIBRILLATION FACT SHEET

Atrial fibrillation is the most frequent cardiac arrhythmia.

It is estimated that 12.1 million people in the United States will have AFib in
2030.1,2

In 2019, AFib was mentioned on 183,321 death certificates and was the
underlying cause of death in 26,535 of those deaths. 3

People of European descent are more likely to have AFib than African Americans.

Because the number of AFib cases increases with age and women generally live
longer than men, more women than men experience AFib.
NICE CG36 Atrial fibrillation 2006 2. Wolf PA et at. Stroke [Link]-988: 3. Paciaroni M et al. Stroke [Link]-430
 GLOBAL ATRIAL FIBRILLATION FACT SHEET

Atrial fibrillation is a major risk factor for ischemic stroke and provokes
important economic burden along with significant morbidity and mortality.

Stroke prevalence increase nearly 5 folds when AFib is present.

In patients with AF, blood clots tend to form in the atria, particularly within
the left atrial appendage (LAA) , due to abnormal blood flow and pooling.

These clots may travel to the brain, causing an ischemic stroke

Around 20% of ischemic strokes are caused by blood clots originating in the
heart (cardio embolic); of these, AF is the most common cause.
NICE CG36 Atrial fibrillation 2006 2. Wolf PA et at. Stroke [Link]-988: 3. Paciaroni M et al. Stroke [Link]-430
 AF-related stroke can be preventable

By preventing thrombus formation in the

heart (thrombo-prophylaxis)
Antithrombotic therapy reduces the risk of stroke and
thromboembolism but also increases the risk of
bleeding.

 Clinical decision-making requires an

assessment of benefit—risk
Patients with AF have an approximately fivefold increased Risk of
Ischemic Stroke:

Framingham Heart Study (N = 5,070)

60
*Patients were seldom
2 Years Age-adjusted incidence

50
treat with antithrombotic
therapy when this study
of Stroke/1,000

was performed in line with

40 clinical practice at the
time.
30

20

10

0
Individuals without AF Individuals wit AF*
 Stroke Risk Scoring in Atrial Fibrillation Patient
Risk CHADS2 CHA2DS2-VASc
Congestive Heart Failure 1 Point 1 Point
Hypertension 1 Point 1 Point
Age 74 Years or older 1 Point 2 Points
Diabetes 1 Point 1 Point
Stroke history 2 Points 2 Points
Vascular Disease 1 Point
Age 65-74 Years 1 Point
Sex Category (Female) 1 Point

CHADS2: Maximum Possible Score of 6, Use Anticoagulant in patient with Score of 2 , Consider Anticogulant for Score of 1.
CHA2DS2-VASc : Maximum Possible Score of 9, Use Anticoagulant in patient with Score of 2 , Consider Anticogulant for Score of 1.
If female sex is the only risk factor, it should not be conferred to CHA2DS2-VASc score of 1. It is a contribute only when other risk factors are present.

Score 6 increases the annual risk of stroke 18.2%

 CHA2DS2-VASc Risk Scoring for AF patients and
Thromboprophylaxis Guidelines (ESC)

Stroke Risk
Score Stroke Prophylaxis Recommendation
Male Female

(Male) – Start Anticoagulant Therapy

>2 High Medium (Female) – Consider Anticoagulant Therapy

1 Medium Low (Male) – Consider Anticoagulant Therapy

0 Low Low Anticoagulant Omitted.

 Stroke Prevention Guideline in AF : ESC 2020

Mechanical heart valves or moderate or severe mitral stenosis Yes

No
Estimate Stroke Risk

CHA2DS2-VASc 0 or
women without other CHA2DS2-VASc 1 CHA2DS2-VASc >2
risk factors

Oral anticoagulation
No antiplatelet or Oral anticoagulation indicated
Assess for contra-indications
anticoagulant treatment should be considered
Correct reversible bleeding
risk factors

NOAC = Non-vitamin K oral anticoagulant (apixaban, dabigatran, edoxaban, rivaroxaban).

preferred
VKA = Vitamin K oral anticoagulant (e.g. warfarin, with INR 2.0–3.0 and time in therapeutic
range kept as high as possible and closely monitored). Other Options*
*No Anti-Coagulation, or left atrial appendage exclusion if clear contra-indications for NOAC VKA
anticoagulation.
 Traditional Anticoagulant: Limitation

UFH: Oral VKAs:

I. Parenteral Administration I. Narrow therapeutic window
II. Monitoring and dose adjustment required II. Unpredictable anticoagulant
III. Risk of HIT III. Prolong half-life
IV. Slow onset and offset
LMWH: V. Significant Interaction with food and drugs
I. Parenteral admiration so dietary restriction.
II. Weight-adjusted dosing (for obese patients) VI. Frequent monitoring and dose adjustment
III. Renal Failure required
Important Benefits of Novel OACs Over VKAs

Reduce potential for Drug and No Need for Coagulation

Fast onset Monitoring
Food Interaction

Predictable
anticoagulation Simplified, fixed dosing
regimen Wide Therapeutic Index

Less labour-intensive Less impact on patients’ daily Improved

life compliance

Reduced administrative Improved Quality of Improved benefit-risk

costs Life profile
Comparative Analysis of Oral Anti-Coagulants
 FDA APPROVED INDICATIONS FOR

RIVAROXABAN:
July 1, November November October October October December
2011 4, 2011 2, 2012 30, 2017 11, 2018 14, 2019 20, 2021

FDA Expands Use of

Prevent Prevent Stroke in FDA Approves Two
FDA Approves 10 m New Indications for
Deep Vein Thrombo People With atrial Rivaroxaban g Dosing for to Red Reduce the Risk of FDA Approves Rivar
sis in Patients Unde Fibrillation. uce the Continued Major Cardiovascul oxaban to Help Prev Rivaroxaban
to Treat, Reduce Re ent Blood Clots in A
rgoing Knee or Hip currence of Blood C Risk of Venous Thro ar Events in Patients to Help Prevent and
Replacement Surger mboembolism (VTE with CAD or PAD cutely Ill Medical Pa Treat Blood Clots in
lots tients
y ) Pediatric Patients
.
. .

Current indications for which Rivaroxaban( ) is approved for use

in clinical practice.
 Oral FXa Inhibitor Use Continues to Grow
9

• More than 8 million patients are 8

8
currently on FXa inhibitors in the US
7 6.5
• Projected 26 million worldwide by 2025
6
• Guideline endorsements
5

Million Patients
5

4
• AHA/ACC/HRS 4

3
3

• CHEST 2

1
• ESC
0
January. J Am Coll Cardiol. 2019;74:104. Lip. Chest. 2018;154:1121. Steffel. Eur Heart J. 2018;39:1330. 2016 2017 2018 2019 2020
Individual Oral Anticoagulant Prescription Claims as a Proportion of Total Oral
Anticoagulant Prescription Claims Among Medicaid Beneficiaries Over Time
Rivaroxaban Clinical Trials:
Advancing the Management of Venous
Arterial Thromboembolism

ROCKET AF
EINSTEIN DVT, EXT, PE
RECORD I TO IV
 Rivaroxaban Trials in Atrial Fibrillation:

The findings of ROCKET AF indicate that once-daily Rivaroxaban would be an effective

alternative to warfarin for stroke prevention in patients with non-valvular AF
N ENGL J MED 2011; 365 (10): 883-89
 Rivaroxaban Trials in DVT & PE:

The single-drug approach of oral Xarelto combines good efficacy with a favorable safety
profile in the acute treatment of DVT and PE, and the long-term secondary prevention of VTE.
N ENGL J MED 2010; 363: 2499–2510, 2012; 366:
1287–1297
 Rivaroxaban Trials in Hip & Knee Replacement Surgery :

Rivaroxaban was significantly more effective than enoxaparin for Thromboprophylaxis in

patients undergoing elective hip replacement surgery.
One tablet of Xarelto 10 mg once daily was superior to subcutaneous enoxaparin 40 mg:

N ENGL J MED 2008; 358: 2765–75

Rivaroxaban Dosage with Renal impairment
Consideration:Right Dose for Right
Patients:
ESC Guidelines Recommendation for PE
 Rivaroxaban Mechanism of Action

Rivaroxaban Selectively blocks the

active site of FXa in the coagulation
pathway.

Rivaroxaban Inhibit free FXa (including

FXa within prothrombinase complete
and clot-bound FXa) and Prothrombinase
activity.

Rivaroxaban has no direct effect on platelet

aggregation but indirectly inhibit platelet
aggregation induce by thrombin, by inhibiting FXa,
Rivaroxaban decrease thrombin generation.
https:// [Link]/products/xarelto/medical-content/xarelto-mechanism-of-action
Approved Clinical Indications
A New Era with Novel Anticoagulant
A New Era with Novel Anticoagulant