Transcript Anticoagulation Update - Sheffield PRESS Portal

Anticoagulation Update
Rhona Maclean
[email protected]
By the end of this session you will
know:
• What anticoagulant therapies are currently
available
• What anticoagulants can be used in particular
clinical situations
• Practical tips in using anticoagulants
– Starting/ switching/ procedures
• Current STH pathway for management DVT/PE
Available Anticoagulant Therapies
Heparins
Vitamin K
Antagonists
NOACs
Unfractionated
Heparin
Low molecular
weight heparin
Warfarin
Dabigatran
Fondaparinux
Phenindione
Sinthrome
Rivaroxaban
(Acenocoumarol)
Apixaban
Heparin and Fondaparinux
Immediate onset of anticoagulation
Warfarin Mode of Action
Prothrombin
Prothrombin
precursor
----
Carboxylase
Reduced vitamin K
Oxidised vitamin K
Vitamin K epoxide reductase
Warfarin
Onset of action- >5 days; not until INR >2 for 24hrs
Vit K dependent
Coagulation factors
FII
FVII
FIX
FX
Mode of Action NOACs
Novel Oral Anticoagulants (NOACs)
Dabigatran
Rivaroxaban
Apixaban
Half life
12-17h
5-13h
9-12h
Administration
Oral
Oral
Oral
Renally excreted?
+++
+/-
+/-
Heparin Induced
Thrombocytopenia
-
-
-
Osteoporosis
-
-
-
Side effects
Dyspepsia in 8-10%
-
-
Monitoring?
No
No
No
Dietary/ drug
interactions
+
+
+
Reversal agent?
?
?
?
Drug Interactions with NOACs
Increase anticoagulant
effect
Dabigatran
Rivaroxaban
Apixaban
Amiodarone (caution)
Azole Antimycotics
Azole Antimycotics
Verapamil (caution)
HIV Protease Inhibitors
HIV Protease Inhibitors
Azole antimycotics
Dronaderone
Dronaderone
Rifampicin
Rifampicin
Rifampicin
Carbamazepine
Carbamazepine
Carbamazepine
Phenytoin
Phenytoin
Phenytoin
Phenobarbital
Phenobarbital
Phenobarbital
St John’s wort
St John’s wort
St John’s wort
Tacrolimus
Cyclosporin
HIV protease inhibitors
Dronaderone
Reduce anticoagulant
effect
Licensed and NICE approved
indications for NOACs
• Dabigatran:
– VTE prevention after elective hip or knee replacement surgery
– Stroke prevention in Atrial Fibrillation
• Rivaroxaban:
–
–
–
–
–
VTE prevention after elective hip or knee replacement surgery
Stroke prevention in Atrial Fibrillation
Deep Vein Thrombosis treatment and secondary prevention
Pulmonary Embolism treatment and secondary prevention
Acute coronary syndromes
• Apixaban:
– VTE prevention after elective hip or knee replacement surgery
– Stroke prevention in Atrial Fibrillation
Risk of adverse events in patients with atrial
fibrillation taking warfarin :
Warfarin is an effective drug
Optimal level of oral anticoagulant therapy
Torn M et al, Arch Int Med 2009; 169:203-1209
Tips for achieving good warfarin
control and avoid complications
• Patient education and engagement
• Encourage stable lifestyle
• Minimise other drug changes/ choose drugs less likely
to interact with warfarin
• Use standardised induction regimen
• Adjust warfarin dose cautiously (+/- 10% of weekly
dose) when outside therapeutic range
– Consider patient’s previous response
• Don’t blindly follow CCDS (INR star)
• Do INR if change of medication likely to interact or if
unwell/ bleeding
Unstable Warfarin Anticoagulation
INR Results
20
16
12
8
4
0
09/09/2006
08/10/2006
06/11/2006
05/12/2006
03/01/2007
01/02/2007
03/01/2007
01/02/2007
Dosage
100
80
60
40
20
0
09/09/2006
08/10/2006
06/11/2006
05/12/2006
68 year old woman on warfarin for recurrent VTE INR 3.5
Rivaroxaban
Warfarin
Event rate/100 patient years
Major and non
major clinically
relevant bleeding
14.9
14.5
Major bleeding
3.6
3.4
Critical bleeding
0.8
1.2
Intracranial
bleeding
0.5
0.7
Clinical Benefit of Anticoagulants in AF
Banerjee et al, T&H 2012
What anticoagulant to use in AF?
• Warfarin
– Pros
•
•
•
•
•
Experience
Efficacious
Long half life
Reversal agent
Use in renal failure
– Cons
•
•
•
•
•
Requirement for monitoring
Variable dosing requirements
Not immediate onset of action
Drug interactions/ lifestyle issues
Bleeding Risk
What anticoagulant to use in AF
• NOACs
– Pros
•
•
•
•
•
Immediate onset of action
Once or twice daily medication- dosette boxes
No (little) monitoring required
Few drug interactions
Risk major bleeding reduced, particularly intracranial
– Cons
•
•
•
•
New- as yet relatively unfamiliar
Shorter half life- compliance issues?
Lack of specific reversal agent- as yet…
Cannot use in renal failure
How to start NOAC in patient with AF
• Counsel patient- it is an anticoagulant
• Check baseline bloods (FBC, renal and liver
biochem)
• Start NOAC (Rivaroxaban with food- in morning?)
• See patient for review in 3-4 weeks- any
problems?
• Check FBC, biochemistry, 3-12 monthly
dependent on patient factors
• Reinforce compliance whenever possible
Which anticoagulant to use for VTE?
• After a first VTE event, patients require
minimum 3 months anticoagulation
• If idiopathic or ongoing risk factors, consider
longer term anticoagulant treatment (NICE)
• Patients require immediate anticoagulation
• If start warfarin, usually entails 8-15
anticoagulation visits in first 3 months of
treatment
EINSTEIN DVT and EINSTEIN PE pooled
analysis: primary efficacy outcome
Cumulative event rate (%)
3.0
Enoxaparin/VKA
N = 4131
2.5
2.0
Rivaroxaban
N = 4150
1.5
HR=0.89; p non-inferiority <0.0001
1.0
Mean time in therapeutic range = 61.7%
0.5
0.0
0
30
60
90
120
150
180
210
240
270
300
330
360
Time to event (days)
Number of patients at risk
Rivaroxaban
4150
4018
3969
3924
3604
3579
3283
1237
1163
1148
1102
1034
938
Enoxaparin/VKA
4131
3932
3876
3826
3523
3504
3236
1215
1149
1109
1071
1019
939
ITT population
EINSTEIN DVT and EINSTEIN PE pooled
analysis: major
bleeding
First major bleeding
Cumulative event rate (%)
3.0
2.5
Rivaroxaban
n/N (%)
Enoxaparin/VKA
n/N (%)
HR (95% CI)
p-value
40/4130
(1.0)
72/4116
(1.7)
0.54 (0.37–0.79)
p=0.002
2.0
Enoxaparin/VKA
N=4116
1.5
1.0
Rivaroxaban
N=4130
0.5
0.0
0
30
60
90
120
150
180
210
240
270
300
330
360
Time to event (days)
Number of patients at risk
Rivaroxaban
4130
3921
3862
3611
3479
3433
2074
1135
1095
1025
969
947
499
Enoxaparin/VKA
4116
3868
3784
3525
3394
3348
1835
1109
1065
990
950
916
409
Safety population
Rivaroxaban for VTE
• Currently in patients with a first DVT without
contraindications
– Eg pregnancy, breastfeeding, renal failure, interacting drugs
• 15mg bd for 3 weeks then
• 20mg od for 10 weeks
• ?Reduce dose in renal impairment
– A reduction of the dose from 20 mg once daily to 15 mg once
daily should be considered if the patient's assessed risk for
bleeding outweighs the risk for recurrent DVT and PE
• Consider duration of treatment
– Reassess after 3 months
• Idiopathic/ recurrent events
– Long term rivaroxaban?
LMWH for patients with VTE and cancer
Lee A et al, NEJM 2003
LMWH for treatment VTE
• Dalteparin 200iu/kg once daily
– In pregnancy currently use bd dosing.
• SPC caps dose at 18,000iu od if >83kg- good
evidence that need to increase dose in those
with high body weight- STH guideline
• After 30 days reduce dose (as per BNF/ STH
guideline)
• Patients with cancer- watch weight and renal
function- may need to adjust dose
Summary: Anticoagulation for VTE
• Patient choice
• Rivaroxaban after a first VTE event (unless
contraindicated), if unstable, side effects or
contraindications to warfarin
• LMWH if cancer, pregnant, interacting drugs
with rivaroxaban
– Once chemotherapy finished, consider switching
from LMWH to alternative anticoagulant
• Warfarin if renal failure, if recurrent events
Mechanical Heart Valves
• Do not use NOACs
• Study of dabigatran terminated as excess
bleeding and thrombosis in dabigatran groups
compared with warfarin.
• No other studies underway at present
Converting from Warfarin to
Rivaroxaban
• Discuss with patient
• Check that patient is not on interacting drugs
• Baseline bloods- FBC, renal and liver
biochemistry, INR
• Make switch
• Review in a couple of weeks for side-effects and
to reinforce compliance
• FBC and biochemistry every 3-12 months
Converting from Warfarin to Rivaroxaban
Stop VKA
VKA
VTE treatment
INR < 2.5
Monitor INR
Commence Xarelto at appropriate dose
SPAF
INR < 3.0
VTE
INR ≤ 2.5
Xarelto SmPC
SmPC for rivaroxaban
L.GB.12.2012.1370 Date of preparation Jan 2013
28
Converting from Rivaroxaban to Warfarin
Standard VKA dose
Xarelto
(dose according to indication)
INR adapted VKA dose
Xarelto can be stopped once INR
> 2.0
INR testing before Xarelto
administration
Days
Once Rivaroxaban is discontinued, INR testing may be done reliably at least
24hrs after the last dose
Xarelto SmPC
Preoperative management of Rivaroxaban
anticoagulation
Major surgery
Minor surgery
Postoperative Management of Rivaroxaban
Anticoagulation
Major surgery
Surgery
D +1
D+2
Prophylactic dalteparin once daily
starting 6 – 8 hrs post op
D+3
D+4
D+5
D+6
Stop dalteparin the day before restarting
therapeutic rivaroxaban (at day 3 – 5, at
earliest on day 3, depending on bleeding
tendency). Check U&E/LFT. Do not restart
therapeutic anticoagulation with epidural in
situ.
Minor surgery
Start Rivaroxaban 24 hours after the procedure.
Patients admitted on prophylactic doses of rivaroxaban (10 mg OD) may be re-started 6 8 hours post op.
Patient pathway for VTE
Diagnosed in A&E or as an inpatient
Seen by thrombosis nurse
specialist for
assessment
MDT
Malignancy suspected
2 weeks O.P.A
with consultant
Unprovoked DVT
4 to 6 weeks O.P.A
with consultant
Provoked DVT
Nurse-led pathway
Conclusion
• Warfarin and NOACs both efficacious in
prevention stroke in AF and treatment VTE
• Most important issue is patients who require
anticoagulation have access to anticoagulant
treatment