update nella fibrillazione atriale stefano fumagalli - sigg.it · unità di terapia intensiva...
TRANSCRIPT
Update nella fibrillazione atriale
Stefano Fumagalli
Unità di Terapia Intensiva Geriatrica e Unità di Aritmologia Geriatrica,
AOU Careggi e Università di Firenze
SimposioLA NUOVA TERAPIA ANTICOAGULANTE NEL GRANDE ANZIANO:
ABBIAMO LE EVIDENZE?
Age >85 years15% of population
Pa
tie
nts
in
itia
tin
g O
AC
(N/m
on
th)
Tre
atm
en
t (%
)
P=0.0002
P<0.0001
P<0.0001 P<0.0001
P<0.0001
P<0.0001
P<0.0001
Months
Number of AF patients who initiate OAC per month (left), and time
trends of treatment prescription in >85 years subjects (right)(N=43299, the Danish nationwide registries, 2011–2015)
Staerk L, 2016
The probability of initiating oral anticoagulation according to age:
The reference group is < 65 years of age(N=43299, the Danish nationwide registries, 2011–2015)
Staerk L, 2016
OR Age groups (years)
<65 65-74 75 - 84 >85
VKA Ref 0.93 1.05 0.81 (0.75-0.87)
Dabigatran Ref 0.88 0.73 (0.69-0-78) 0.65 (0.60-0-70)
Rivaroxaban Ref 1.20 (1.10-1.31) 1.14 (1.04-1.24) 1.52 (1.38-1.67)
Apixaban Ref 1.33 (1.22-1.45) 1.49 (1.37-1.63) 2.09 (1.89-2.30)
1
1,25
1,56
0,86
1,73
2,19
0
0,5
1
1,5
2
2,5
<65 65-74 ≥75
2,74 2,67
5,42
2,56
3,46
5,97
0
1
2
3
4
5
6
7
<65 65-74 ≥75
ApixabanWarfarin
HR=1.07
HR=(0.64-0.94)
HR=0.91
Stroke / Systemic embolism All-cause mortality
Eve
nts
(% /
ye
ar)
Age-groups (years)
HR=1.16
HR=(0.54-0.96)
HR=(0.53-0.95)
P interaction = 0.11 P interaction = 0.43
The effect of apixaban vs. warfarin according to age (1)
Halvorsen S, 2014<65 – N=5471; 65-74 – N=7052; ≥75 – N=5678
13,6
17,9
23,5
19,1
25,9
33,7
0
10
20
30
40
<65 65-74 ≥75
0,310,28
0,43
0,35
0,81
1,29
0
0,4
0,8
1,2
1,6
<65 65-74 ≥75
ApixabanWarfarin
HR=0.87
HR=(0.20-0.60)
HR=(0.20-0.57)
All bleeding Intracranial bleeding
Eve
nts
(% /
ye
ar)
Age-groups (years)
HR=(0.65-0.78)
HR=(0.65-0.77)
HR=(0.65-0.78)
P interaction = 0.94 P interaction = 0.20
The effect of apixaban vs. warfarin according to age (2)
Halvorsen S, 2014<65 – N=5471; 65-74 – N=7052; ≥75 – N=5678
Individual patients
Hem
orr
hag
e v
olu
me (
mL
s)
Individual participants and their corresponding hemorrhage sizes, and box
plot with hematoma volume for NOAC and warfarin cases (age: 80.3 years)
2.4 mL
8.9 mL
P=0.0028N=11
N=52
Univariate analysis
VKA vs. NOAC= +1.61 (0.69-2.53) mL
Lobar vs. Non-L= +1.52 (0.85-2.20) mL
Wilson D, 2016
The PIONEER AF-PCI Study – Prevalence of older patients and rate
of permanent discontinuation of treatment (mean age: 70 years)
Gibson CM, 2016
Group 1 (N=709) - Rivaroxaban 15 mg + P2Y12
Group 2 (N=709) - Rivaroxaban 2.5 mg*2 + DAPT
Group 3 (N=706) - VKA+ DAPT
Pati
en
ts ≥
75 y
ears
of
ag
e (
%)
35,834,6
32,6
0
10
20
30
40
Group 1 Group 2 Group 3
21 21,1
29,4
0
10
20
30
Group 1 Group 2 Group 3
Tx
perm
an
en
tly d
isco
nti
nu
ed
(%
)
P<0.001
Incid
en
ce o
f M
ajo
r
Ad
vers
e C
V E
ven
ts (
%)
Days
Cumulative Incidence of the Secondary Efficacy End Point(composite of death from cardiovascular causes, myocardial infarction, or stroke)
Gibson CM, 2016
Group 1 (N=709)
Rivaroxaban 15 mg +
P2Y12
Group 2 (N=709)
Rivaroxaban 2.5 mg*2
+ DAPT
Group 3 (N=706)
VKA+ DAPT
6.5%
5.6%
6.0%
Incid
en
ce o
f C
lin
icall
y
Sig
nif
ican
t B
leed
ing
(%
)
Days
Cumulative Incidence of the Primary Safety End Point(composite of major bleeding or minor bleeding according to [TIMI] criteria or
bleeding requiring medical attention)
Gibson CM, 2016
Group 1 (N=709)
Rivaroxaban 15 mg +
P2Y12
Group 2 (N=709)
Rivaroxaban 2.5 mg*2
+ DAPT
Group 3 (N=706)
VKA+ DAPT
16.8%HR1 vs. 3 = 0.59
95%CI = 0.47-0.76
18.0%HR1 vs. 3 = 0.63
95%CI = 0.50-0.80
26.7% - Ref.
Steffel J, 2016
Eve
nt
rate
(%
/ye
ar)
Incidence and HR of Efficacy and Safety Endpoints in Patients With (N=900) Versus Without (N=20205) Increased Risk of Falls
HR=1.88
P<0.001
HR=1.45
P<0.001
HR=1.30
P=0.023
HR=1.67
P=0.013
Bleed
Steffel J, JACC 2016
Eve
nts
/ 1
0,0
00
Pat
ien
t Ye
ars
Absolute Risk Reduction of HD Edoxaban Regimen Compared With Warfarin in Patients at Increased Versus Not at Increased Fall Risk
NNT
157 vs. 500
Bleed
NNT
57 vs. 257
NNT
94 vs. 323
NNT
152 vs. 293
Adjusted Kaplan-Meier Incidence Plots of Thromboembolic Stroke
in Patients Treated With Dabigatran or Rivaroxaban(Medicare persons aged 65 years and older; 2011-4)
Rivaroxaban (N=66651)
7.7 . 1000 p-years
Dabigatran (N=52240)
9.7 . 1000 p-years
P=0.07
HR=0.81
-1.8 events
Graham DJ,
2016
Adjusted Kaplan-Meier Incidence Plots of Intracranial Hemorrhage
in Patients Treated With Dabigatran or Rivaroxaban(Medicare persons aged 65 years and older; 2011-4)
Rivaroxaban (N=66651)
5.8 . 1000 p-years
Dabigatran (N=52240): 3.7 . 1000 p-years
P=0.002 HR=1.65
(1.20-2.26)
+2.3 events
Graham DJ,
2016
Adjusted Kaplan-Meier Incidence Plots of Major Gastrointestinal
Bleeding in Patients Treated With Dabigatran or Rivaroxaban(Medicare persons aged 65 years and older; 2011-4)
Rivaroxaban (N=66651)
32.5 . 1000 p-years
Dabigatran (N=52240)
23.3 . 1000 p-years
P<0.001
Graham DJ,
2016
HR=1.40
(1.23-1.59)
+9.4 events
Adjusted Kaplan-Meier Incidence Plots of Mortality in Patients
Treated With Dabigatran or Rivaroxaban(Medicare persons aged 65 years and older; 2011-4)
Rivaroxaban (N=66651)
24.7 . 1000 p-years
Dabigatran (N=52240)
22.2 . 1000 p-years
P=0.051
Graham DJ,
2016
HR=1.12
(1.00-1.32)
+3.1 events
First choice In patients older than 75 years, we suggest apixaban 5 mg twice daily (2.5 mg if >2 of the following: age >80 years, body weight <60 Kg, or creatinine >1.5 mg/dL)
Second choice dabigatran 110 mg twice daily, rivaroxaban 20 mg once daily, or edoxaban 60 mg once daily
Non-vitamin K oral anticoagulants and age
Diener HC2016
43 centri aderenti
Centri partecipanti: distribuzione geografica
17
Strumenti di Raccolta dati cartacei: quando?
V1:
visita di
arruolamento
V2
visita di follow-up
V3
visita di follow-up
A 3 mesi A 6 mesi
o
Alla fine del
trattamento con
Apixaban
18
Disegno dello studio - 1
•40 centri italiani partecipanti
•Terapia con Apixaban per NVAF, VTE/PE
•6 mesi di osservazione
• Normale pratica clinica
Osservazionale Prospettico
NazionaleCoorte
APULEIO
Study protocol - Version1.2, 4 November 2015 19