Diapositiva 1

XXV Congresso Nazionale FCSA
Bologna, 13-15 Ottobre 2014
I DOAC nel tromboembolismo venoso
Gualtiero Palareti
Prof. Malattie Cardiovascolari
Università di Bologna
Timing and therapies of VTE
Initial and for 3 mo.
LMWH
Fondap.
UFH
DOAC
Secondary prevention:
VKA
DOAC
(LMWH)
a) Yes or not?
b) How long?
c) Which drug?
VKA
DOAC
(LMWH)
Terapia iniziale:
Importante differenza tra gli studi sui
DOC in TEV
•
•
Terapia parenterale per i primi 5-9 gg per tutti
poi DOAC vs standard terapia
- dabigatran
- edoxaban
Subito DOAC vs standard terapia
- rivaroxaban
- apixaban
DOACs for acute phase VTE treatment
Trial
Drug
Design
Dose
Initial treatment
RE-COVER
(Schulman NEJM 2009)
RE-COVER II
(same design)
Dabigatran
(Pradaxa)
Anti-IIa
Double-blind
150 mg BID
Parenteral ACs in first
5-7 d; then dabigatran
EINSTEIN DVT
(Bauersachs NEJM 2010)
EINSTEIN PE
(Buller NEJM 2012)
Rivaroxaban
(Xarelto)
anti-Xa
Open-label
15 mg BID for the first
3 weeks followed by
20 mg OID
Single drug
AMPLIFY
(Agnelli NEJM 2013)
Apixaban
(Eliquis)
anti-Xa
Double-blind
10 mg BID for the first
7 d. followed by 5 mg
BID
Single drug
HOKUSAI
(Buller NEJM 2013)
Edoxaban
(Lixiana)
anti-Xa
60 mg OID
Parenteral ACs in first
(30 mg in high risk pts) 5-7 d; then edoxaban
2009
randomized, double-blind, noninferiority trial in patients with acute
VTE who were initially given parenteral anticoagulation for a median of 9 d.
oral dabigatran, 150 mg BID versus warfarin (2.0 to 3.0 INR)
NEJM 2009
2010
“Einstein PE e DVT” studies
VTE: Random., open-label,15 mg bid x 3
weeks; then 20 mg oid; vs standard therapy;
variable duration
Rivaroxaban
Recurrent VTE
36 (2.1%)
Fatal PE
1
Non Fatal PE 20
Standard
51 (3.0%)
Recurrent VTE
0
18
HR
0.68 (0.44-1.04)
Major or CRNM bleeding
Rivaroxaban
Standard
8.1% (major 0.8%)
8.1% (major 1.2%)
2012
2013
NEJM 2013
Hokusai VTE: Efficacy outcomes
Edox. (4118) W (4122)
HR
P Value
First recurrent VTE
Overall study period
130 (3.2)
146 (3.5)
0.89
<0.001
Patients with index DVT*
83 (3.4)
81 (3.3)
1.02
Patients with index PE**
47 (2.8)
65 (3.9)
0.73
On-treatment period
66 (1.6)
80 (1.9)
0.82
Subgroup severe PE
(RVD/ProBNP) n/N (%)
15/454 (3.3)
30/485 ( 6.2) 0.52
<0.001
From Palareti G., Semin Hematol 2014
Extended treatment
DOACs for extended VTE treatment
Trial
Drug
Design
Dose
Design
RE-MEDY
RE-SONATE
(Schulman NEJM 2013)
Dabigatran
(Pradaxa)
Double-blind
150 mg BID
Vs warfarin
Vs placebo
EINSTEIN DVT
(Bauersachs NEJM 2010)
EINSTEIN PE
(Buller NEJM 2012)
Rivaroxaban
(Xarelto)
Open-label
20 mg OID
Vs placebo
AMPLIFY
(Agnelli NEJM 2012)
Apixaban
(Eliquis)
Double-blind
Vs placebo
After 6-12 mo from 1st therapy
Randomization to two doses:
2.5 BID or 5 mg BID
HOKUSAI
(Buller NEJM 2013)
Edoxaban
(Lixiana)
Double-blind
60 mg OID (30 mg in high
risk)
Vs warfarin
Einstein-Extension
Design of the study
• After first 6 m treatment for acute VTE
• 1197 pts randomized to further 6 m with
- Xarelto 20 mg od
- Placebo
Recurrent VTE
7.1%
1.3%
Major bleeding 0.7% - CRNM bleeding 5.4%
2013
In two double-blind, randomized trials, dabigatran at a dose of
150 mg twice daily was compared with warfarin or with placebo in
patients with VTE who had completed at least 3 initial
months of therapy.
NEJM 2013
NEJM 2013
NEJM 2013
From Palareti G., Semin Hematol 2014
Major bleeding in phase 3 trials of NOACs vs VKA therapy in VTE
Recurrent VTE in phase 3 trials that compared a NOAC with VKA
therapy in patients with VTE
From Barco et al.,
T&H
2013
• Xarelto: Gazzetta Ufficiale, 29 agosto 2013
• Trattamento della TVP e prevenzione della TVP
recidivante e dell’ EP dopo TVP acuta
nell’adulto.
• Pradaxa approvato da
• FDA (Aprile 2014)
• EMA (Giugno 2014): “…treatment and prevention of
recurrence of deep vein thrombosis and
pulmonary embolism”, sia il 150 che il 110 mg
bid
Eliquis® (apixaban) Receives CHMP Positive Opinion for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism
Friday, June 27, 2014 - 7:00am EDT
Apixaban
EMA
Commenti personali
•
•
•
•
•
> scelta terapeutica in generale
> scelta per singoli pazienti (compliance, ecc.)
Tutti non inferiori per efficacia (anche per EP)
Tendenza a < emorragie (significativa per alcuni)
Evitata l’instabilità e difficoltà iniziale degli AVK (con
potenziali effetti su recidiva)
• Potenziale > facilità per il trattamento esteso

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