Transcript Safety and antidotes of noacs

Safety and antidotes
of NOACS
Mr.Mohamed Omar Elfarok , M.Sc, FRCSENG,FRCSED,IME
Novel Anticoagulants – 5 years old
NOAC
DOAC
TSOAC
Novel Oral Anti Coagulant
Non Vitamin K antagonist Oral Anti Coagulant
Direct acting Oral Anti Coagulant
Target Specific Oral Anti Coagulant
Nomenclature

Xaban = direct Xa inhibitor

Gatran = direct thrombin inhibitor

Paranux = indirect Xa inhibitor
Four Novel Agents
Dabigatran / Paradaxa
Rivaroxaban / Xarelto
Apixaban / Eliquis
Endoxaban / Savaysa
All with generally comparable safety safety and efficacy
BUT each has multiple unique characteristics and
considerations
Studies
Safety
Why NOACs
Safety
Safety
NOACS Monitoring
*Monitoring drug effect may be needed for :
1-Renal insufficiency , hepatic insufficiency
2-Extremes of weight
3-Bleeding
-spontaneous , trauma , induced , surgical
- overdose
4-Drug failure :stroke or systemic embolization
competence vs true lack of efficacy
*Target ranges not established
*No validated data
NOACS monitoring

Anti Xa chromogenic assays should be used to determine plasma
concentration of direct Fxa inhibitors

For rivaroxaban the PT is usually more sensitive than the APTT but cannot be
used to determine the drug concentration

For apixaban both PT and APTT are insensitive and patients may have normal
coagulation times despite therapeutic concentrations
Major bleeding TSOACS vs Warfarin
Incidence of major bleeds
NOAC
-43050 patients
-2158 major bleeds (5.01)
VKA
-29911 patients
-1826 Major bleeds (6.1%)
18% reduction in major bleeds
Caldeira et al Heart 2015;101:1204-1211
Major bleeding TSOAC vs Warfarin
incidence of fatal bleeds
NOAC
-43050 patients
-121 fatal bleeds (0.28%)
VKA
-29911 patients
-152 fatal bleeds (0.51%)
NOACS associated with a 47 % odds reduction in the risk of fatal bleeding Or 0.53
95% CI 0.42-0.68
Caldiera et al Heart 2015 ;101:1204-1211
Major bleeding case fatality
Meta-analysis of 12 studies
Case fatality rate of major bleeding
-DOAC
7.5 % (30% reduction )
-VKA
11.05%
Fatal bleeding per 100 patients yerrs
-DOAC
0.16%
-VKA
0.32%
Crowther et al Thromb Haedmost 2015;13:2012-20
Bottom line
Major bleeding events are more frequent with warfarin than with
TSOACs
A patient who has a major bleeding event while on warfarin is more
likely to die from it than a patient on a TSOAC
Even in the absence of a reversal agent for TSOAC
Antidote
Approach to TSOAC associated bleeding
Find and fix the leak !
Everything else is ancillary
Managing bleeding complications in
patients treated with DOACs
Initial assessment
-hemodynamic stability
-source of bleeding
-time since last dose of anticoagulant
- which anticoagulant
-renal function
-interacting medications
Risk stratify
Managing bleeding complications in
patients treated with DOACs
Minor bleeding
-local hemostatic measures
-consider anticoagulant without based on
balancing bleeding and thrombosis risk
Managing bleeding complications in
patients treated with DOACs
Moderate bleeding
-General measure
-anticoagulant withdrawal
-mechanical compression
-monitor hemodynamic status
-volume replacement
-definitive interventions
-blood product transfusions
-RBC if anemic
-FFP or platelets
- FEIBA Factor Eight Inhibitor Bypassing Activity
Managing bleeding complications
Patients treated with DOACs
Life threatening bleeding
-everthingthat is being done for moderate
-intensive care setting , hemodynamic support
-nonspecific antidotes 4 factor PCC
activated PCC
-Specific reversal
Idarucizumab,andexanet
-Adjuventive therapic desopressin ,
antifibrinolytics , charcoal
What to consider before reversal ?
IS a DOAC present ?
When was the last dose ?
Does it need to be reversed ?
If so with specific or nonspecific reversal
Limitations of Reversal Agents
Reversal agents can only eliminate the antoicoagulant contribution to the
bleeding problem .They rarely stop the bleeding because they do not fix
the problem
Most deaths from major bleeding occur in patient NOT an anticoagulants or
other blood thinners
Do we really need reversal agents ?
Annual rate of major bleeding remains at 2-3% in the AF population
Even with NOACS annual rate of intracranial hemorrhage is 0.1 -0.5 % in the
AF population
Some patients may require reversal because of trauma or need for urgent
surgery
The future of reversal
The coming years will be exciting as we continue to
refine our management of these TSOACs and explore the
boundaries of reversal
And there are already novel classes of anticoagulants on
horizon as anti FXII or FXI
Thank you