NEW GENERATION ORAL

ANTICOAGULANT
which act by diretly inhibiting the
factor Xa
•Prophylaxis of DVT and PE.
(10 mg oral OD)

•Treatment of DVT and PE.

(15 mg BD for 3 weeks than
20 mg OD)
• Prevention of Recurrent DVT
and VTE
(20 mg oral OD)

• Non-valvular Atrial fibrilation to

reduce the risk of stroke and
systemic embolism
In the reduction of major
CARDIOVASCULAR
EVENTS
RIVAROXABAN WITH OR WITHOUT ASPIRIN IN STABLE
CARDIOVASCULAR DISEASE
 Background:
Heart failure (HF) affects over 26 million people worldwide and the
incidence is expected to increase dramatically over the next decade

HF with atherosclerotic coronary artery disease (CAD) and/or

peripheral artery disease (PAD) leads to increased cardiovascular
events compared to those without CAD or PAD

Ambrosy AP, et al. J Am Coll Cardiol 2014;63:1123-33. Shah KS, et al. J Am Coll Cardiol 2017;70:2476-2486.
Jones WS, et al. Am J Cardiol;2011;108:380-384.

10
11
COMPASS Design
Cardiovascular Outcomes for People Using Anticoagulation Strategies
27,325 patients with stable
CAD or PAD
• Randomized, placebo
controlled, double blinded
1,323 with a primary outcome
trial event
Rivaroxaban 2.5 mg bid
• Ongoing arm testing + aspirin 100 mg daily

proton pump inhibitor Rivaroxaban 5 mg bid

Median
Follow Up:
pantoprazole versus R 23 months (1.9 years)
Run-in
placebo (PPI arm) (aspirin) Aspirin 100 mg daily
602 sites, 33 countries

Czech Republic
N=1553

Italy
N=1018

7
 Baseline characteristics
Rivaroxaban + aspirin Rivaroxaban Aspirin
Characteristic N=9,152 N=9,117 N=9,126
Age, yr 68 68 68
Blood pressure, mmHg 136/77 136/78 136/78
Total cholesterol, mmol/L 4.2 4.2 4.2
CAD 91% 90% 90%
PAD 27% 27% 27%
Diabetes 38% 38% 38%
Lipid-lowering 90% 90% 89%
ACE-I or ARB 71% 72% 71%

13
 Primary: CV death, stroke,
MI
R+A R A Rivaroxaban + Rivaroxaban
N=9,152 N=9,117 N=9,126 aspirin vs. vs. aspirin
Outcome aspirin
N N N HR HR
(%) (%) (%) (95% CI) p (95% CI) p

CV death, 379 448 496 0.76 0.90

<0.0001 0.12
stroke, MI (4.1%) (4.9%) (5.4%) (0.66-0.86) (0.79-1.03)

14
 Primary components
R+A A Rivaroxaban + Aspirin vs.
N=9,152 N=9,126 Aspirin
Outcome N N HR
(%) (%) (95% CI) p
160 203 0.78
CV death (1.7%) (2.2%) (0.64-0.96) 0.02

83 142 0.58
Stroke <0.0001
(0.9%) (1.6%) (0.44-0.76)
178 205 0.86
MI 0.14
(1.9%) (2.2%) (0.70-1.05)

15
 Major bleeding
R+A R A Rivaroxaban + Aspirin Rivaroxaban vs.
N=9,152 N=9,117 N=9,126 vs. Aspirin Aspirin
Outcome
N (%) N (%) N (%) HR (95% HR
P P
CI) (95% CI)
288 255 170 1.70 1.51
Major bleeding (3.1%) (2.8%) (1.9%) (1.40-2.05) <0.0001 (1.25-1.84) <0.0001
15 14 10 1.49 1.40
Fatal (0.2%) (0.2%) (0.1%) (0.67-3.33) 0.32 (0.62-3.15) 0.41
21 32 19 1.10 1.69
Non fatal ICH* (0.2%) (0.4%) (0.2%) (0.59-2.04) 0.77 0.07
(0.96-2.98)
Non-fatal other 42 45 29 1.43 1.57
critical organ* (0.5%) (0.5%) (0.3%) (0.89-2.29) 0.14 (0.98-2.50) 0.06

16
 Net clinical benefit
R+A A Rivaroxaban + Aspirin
N=9,152 N=9,126 vs. Aspirin
Outcome
N (%) N (%) HR (95%
P
CI)

Net clinical benefit 431 534 0.80

0.0005
(Primary + Severe bleeding (4.7%) (5.9%) (0.70-0.91)
events)

17
COMPASS Main Trial Outcomes Riva+ASA vs ASA:
Primary Outcome: MACE (CV death,
stroke or MI) ↓MACE 24%
Median 23 month follow up
↑Net benefit 20%

↓ Mortality 18%
Cumulative

 No benefit for Riva

Hazard

alone
ASA = aspirin; CV = cardiovascular;
MACE = major adverse cardiovascular
events; MI = myocardial infarction;
Time (years) Riva = rivaroxaban.

18
 Conclusion
Rivaroxaban 2.5 mg bid plus aspirin 100 mg
od:
• Reduces CV death, stroke, MI
• Increases major bleeding without a
significant increase in fatal, intracranial
or critical organ bleeding
• Provides a net clinical Benifit over aspirin
alone.
19
Rivaroxaban 2.5mg EMA Approved

the full indications for Xarelto 2.5 mg tablets will be as follows1:

“rivaroxaban) co-administered with acetylsalicylic acid (ASA) alone or with
ASA plus clopidogrel or ticlopidine, is indicated for the prevention of
atherothrombotic events in adult patients after an acute coronary syndrome
(ACS) with elevated cardiac biomarkers (see sections 4.3, 4.4 and 5.1).
 A T L

AS
Rivaroxaban in Patients with a Recent Acute Coronary
Syndrome
 A T L
AS
Background
Acute coronary syndromes arise from coronary
atherosclerosis with superimposed thrombosis. Since
factor Xa plays a central role in thrombosis, the
inhibition of factor Xa with low-dose rivaroxaban might
improve cardiovascular outcomes in patients with a
recent acute coronary syndrome
 A T L
AS
METHOD
In this double-blind, placebo-controlled trial, randomly assigned
15,526 patients with a recent acute coronary syndrome to
receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban
or placebo for a mean of 13 months and up to 31 months.
The primary efficacy end point was a composite of death from
cardiovascular causes, myocardial infarction, or stroke
A T L
AS
CONCLUSION
In patients with a recent acute coronary syndrome,
rivaroxaban reduced the risk of the composite end point of
death from cardiovascular causes, myocardial infarction or
stroke.

Rivaroxaban increased the risk of major bleeding and

intracranial hemorrhage but not the risk of fatal bleeding.
Background:
Dual antiplatelet therapy (DAPT) has been the mainstay of antithrombotic
management for acute coronary syndrome (ACS). Approximately 5-10% of
patients experience recurrent events despite standard treatment, and there is
an unmet demand for secondary cardiovascular prevention in the post-ACS
setting. Combined use of antiplatelet and anticoagulant (“dual-pathway
therapy”) emerges to be an attractive strategy.
Conclusion:
Dual-pathway therapy with rivaroxaban plus aspirin
or a P2Y12 inhibitor may be an effective and safe
alternative to DAPT in the post-ACS setting.
2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-
segment elevation
New Indication for Rivaroxaban Approved By FDA
OCTOBER 12, 2018
A new indication for Rivaroxaban has been approved
NICE Advisors Recommend Rivaroxaban for Secondary by FDA officials.
Prevention in ACS Patients

Triple Antithrombotic Therapy: Risky but Sometimes

Necessary
REVOBAN 2.5 MG
(RIVAROXABAN)
INDICATION
REVOBAN 2.5 co-administered with acetylsalicylic acid (ASA) alone or with ASA
plus clopidogrel or ticlopidine, is indicated for the prevention of atherothrombotic
events in adult patients after an acute coronary syndrome (ACS) with elevated
cardiac biomarkers.

Posology
The recommended dose is 2.5 mg twice daily
Method of administration
Revoban is for oral use.
The tablets can be taken with or without food
REVOBAN 2.5 MG
(RIVAROXABAN)
Half Life
Rivaroxaban has a half-life of approximately 5 to 13 hours
Absorption
Rivaroxaban is rapidly absorbed with maximum concentrations (Cmax) appearing
2 - 4 hours after tablet intake.
Oral Bioavailability
Is high (80 - 100%) for the 2.5 mg
Plasma protein binding
Plasma protein binding in humans is high at approximately 92% to 95%,
REVOBAN 2.5 MG
(RIVAROXABAN)
If a dose is missed
The patient should continue with the regular dose as recommended at the next
scheduled time. The dose should not be doubled to make up for a missed dose.
When to start
Treatment with REVOBAN should be started as soon as possible after stabilisation of
the ACS event (including revascularisation procedures); at the earliest 24 hours after
admission to hospital and at the time when parenteral anticoagulation therapy would
normally be discontinued
Shelf life
3 years
Special precautions for storage
This medicinal product does not require any special storage conditions
REVOBAN 2.5 MG
(RIVAROXABAN)
CONCOMITANT USE
• In ACS patients, efficacy and safety of Revoban 2.5 mg have been investigated
in combination with the antiplatelet agents ASA alone or ASA plus
clopidogrel/ticlopidine.
• Treatment in combination with other antiplatelet agents, e.g. prasugrel or
ticagrelor, has not been studied and is not recommended
• The use of Revoban is not recommended in patients receiving concomitant
systemic treatment with azole-antimycotics (such as ketoconazole, itraconazole,
voriconazole and posaconazole) or HIV protease inhibitors (e.g. ritonavir)
REVOBAN 2.5 MG
(RIVAROXABAN)
CONCOMITANT USE
Care is to be taken if patients are treated concomitantly with
medicinal products affecting haemostasis such as non-steroidal anti-inflammatory
medicinal products (NSAIDs),
selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine
reuptake inhibitors (SNRIs).
REVOBAN 2.5 MG
(RIVAROXABAN)
Adverse reaction
The most commonly reported adverse reactions in patients receiving rivaroxaban
were bleedings
REVOBAN 2.5 MG
(RIVAROXABAN)
FOR ACS
• Patients taking REVOBAN 2.5 mg twice daily should also take a daily dose of
75 - 100 mg ASA or a daily dose of 75 - 100 mg ASA in addition to either a daily
dose of 75 mg clopidogrel or a standard daily dose of ticlopidine.
• Treatment should be regularly evaluated in the individual patient weighing the
risk for ischaemic events against the bleeding risks. Extension of treatment
beyond 12 months should be done on an individual patient basis as experience
up to 24 months is limited
.
REVOBAN 2.5 MG
(RIVAROXABAN)

CAD/PAD
Patients taking REVOBAN 2.5 mg twice daily should also take a daily dose of 75 -
100 mg ASA.
Duration of treatment should be determined for each individual patient based on
regular evaluations and should consider the risk for thrombotic events versus the
bleeding risks.
 REVOBAN 2.5 MG
(RIVAROXABAN)
Special populations
Renal impairment
Use is not recommended in patients with creatinine clearance < 15 ml/min
No dose adjustment is necessary in patients with
mild renal impairment (creatinine clearance 50 - 80 ml/min)
or
moderate renal impairment (creatinine clearance 30 - 49 ml/min)
REVOBAN 2.5 MG
(RIVAROXABAN)
Special populations
Hepatic impairment
REVOBAN is contraindicated in patients with hepatic disease associated with coagulopathy and
clinically relevant bleeding
Elderly population
No dose adjustment.The risk of bleeding increases with increasing age
Body weight
No dose adjustment
Gender
No dose adjustment
Paediatric population
The safety and efficacy of Revoban in children aged 0 to 18 years have not been established. No
data are available. Therefore, Revoban is not recommended for use in children below 18 years of
age.
REVOBAN 2.5 MG
(RIVAROXABAN)
Contraindications
• Hypersensitivity to the active substance or to any of the excipients
listed in section.
• Active clinically significant bleeding.
• Lesion or condition, if considered to be a significant risk for major
bleeding
• Concomitant treatment with any other anticoagulants, e.g. low
molecular weight heparins (enoxaparin, dalteparin, etc.), heparin
derivatives (fondaparinux, etc.), oral anticoagulants (warfarin,
dabigatran etexilate, apixaban, etc.)
REVOBAN 2.5 MG
(RIVAROXABAN)
Contraindications
• Concomitant treatment of ACS with antiplatelet therapy in patients
with a prior stroke or a transient ischaemic attack (TIA)
• Pregnancy and breast-feeding