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