APIXABAN NELLA SPAF21 maggio 2015

ROMA

Dott. Sergio AgostiCardiologo, Ospedale Novi Ligure (AL)www.docvadis.it/agostisergioagostisergio@virgilio.ithttp://www.arcaliguria.it/

SPAF: quale ruolo ha ancora l’ASA?

Introduction to ASA • One of the most widely used drugs of the 20th century1

• Taken by millions of patients worldwide for the treatment and prevention of CVD, and is the most widely tested antiplatelet drug1

• Has been (and is still) used for stroke prevention in AF1,2

ASA = acetylsalicylic acid; CVD = cardiovascular disease; VKA = vitamin K antagonist 1. Dai Y, Ge J. Thrombosis 2012;2012:245037; 2. Camm AJ et al. Eur Heart J 2012;33:2719–47 2

Traditionally considered a safe, but less effective, alternative to VKAs when anticoagulation is contraindicated, or for use in patients at low risk

of stroke1,2

However, this is not consistent with the latest treatment guidelines2

ASA for stroke prevention in AFAIAC and AHA/ACC Guidelines

ASA for stroke prevention in AFESC Guidelines

ASA??

Camm AJ et al. Eur Heart J

NICE 2014 Guidelines on the management of AF2

“Do not offer aspirin monotherapy solely for stroke prevention with atrial fibrillation”

2012 ESC Guidelines1

Current Guidelines do not recommend ASA for stroke prevention in most NVAF patients

1 Camm AJ et al. Eur Heart J 20122 NICE clinical Guideline. 2014. The management of AF

Limited efficacy of ASA in reducing stroke risk in patients with AF

Random effects model; error bars = 95% CI; *P>0.2 for homogeneity; †Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic); for ischaemic stroke only, RRR was 21% (95% CI: −1 to 38%)ASA = acetylsalicylic acid; QOD = every other dayHart RG et al. Ann Intern Med 2007;146:857–67

RRR (%)†100 –10050 0 –50

AFASAK (1989)

SPAF (1991)

EAFT (1993)

ESPS II (1997)

ASA better Placebo better

LASAF (1997)125 mg/d

125 mg QOD

UK-TIA (1999)300 mg/d

1200 mg/d

JAS (2006)T

All trialsRRR: 19%*

(95% CI: –1 to 35%)

Only the SPAF trial showed a benefit of ASA over placebo for reducing stroke risk

ASA was less effective than VKA in historical trials in AF

Random effects model; error bars = 95% CI; *P>0.2 for homogeneity; †Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic); ASA = acetylsalicylic acidHart RG et al. Ann Intern Med 2007;146:857–67 9

RRR (%)†

100 –10050 0 –50

AFASAK I (1990)

BAFTA (2007)

EAFT (1993)

PATAF (1999)

Warfarin better ASA better

Chinese ATAFS (2006)

SPAF II (1994)Age 75 yrsAge >75 yrs

All trials (4620 pt) RRR: 38%*(95% CI: 18-52%)

Risk of major and intracranial bleeding not significantly different between ASA and OAC

*Modified HAS-BLED score used in this study: 1 point each for systolic blood pressure >160 mmHg, renal dysfunction, liver dysfunction, stroke, bleeding, age >65 years, drugs affecting bleeding or alcohol abuse (maximum score = 7); score 0 –2 indicates low bleeding risk, ≥3 indicates high bleeding risk; ASA = acetylsalicylic acidFriberg L et al. Eur Hear J 2012:33:1500-10; Pisters R et al. Chest 2010;138:1093–100

ASA (n=61

396)

Major bleeding

0

5

10

15

20

25

0 1 2 3 4 5 6 7

HAS-BLED total score*

Ble

ed

s/year

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0 1 2 3 4 5 6 7

HAS-BLED total score*

Intracranial bleeding

Ble

ed

s/year

OAC (n=48 599)Tot Pt 182,678

B. Major Bleeding

CharacteristicNo. of

patientsASA Apixaban Hazard Ratio (95% CI)

P value for interaction

No. of events (%/yr)Overall 5599 39 (1.2) 44 (1.4) CHADS2 score 0.70 0-1 2026 6 (0.5) 6 (0.5) 2 1999 14 (1.3) 14 (1.2) ≥ 3 1570 19 (2.1) 24 (2.9)

AVERROES: endpoint principali di efficacia e sicurezza e richio di ictus

Adapted from Connolly et al. N Engl J Med 2011;364:806-17.

A. Stroke and Systemic Embolism

CharacteristicNo. of

patientsASA Apixaban Hazard Ratio (95% CI)

P value for interaction

No. of events (%/yr)Overall 5599 113 (3.7) 51 (1.6) CHADS2 score 0.23 0-1 2026 18 (1.6) 10 (0.9) 2 1999 40 (3.7) 25 (2.1) ≥ 3 1570 55 (6.3) 16 (1.9)

0.05 0.25 1.00 4.00

Apixaban better ASA better

0.05 0.25 1.00 4.00

Apixaban better ASA better

ASA for stroke prevention in AFAIAC and AHA/ACC Guidelines

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

JACC - DOI: 10.1016/j.jacc.2014.03.022

Raviele A et al .G Ital Cardiol 2013;14(3):215-240

Recommendations CORa LOEb

FA with CHA2DS2-VASc score 0 No antithrombotic therapy I B

FA with CHA2DS2-VASc score 1c Warfarin (INR 2.0-3.0) or dabigatran, rivaroxaban, apixaban

IIb B

FA with CHA2DS2-VASc score ≥2

Warfarin (INR 2.0-3.0) or dabigatran, rivaroxaban, apixaban

I A

a: Class of Recommendationsb: Level of evidence.c: in the category CHA2DS2-VASc score 1 there are pt with really low risk for whom is not reccomended any therapy (sex female and age <65 years) or is reccomended aspirin (cardiovascular disease). The presence of renal disfunction (creatinine clearance <60 ml/min) identifies pt at high risk for whom is indicated oral anticoagulant therapy

“… The risk of stroke in the pt with CHA2DS2-VASc score = 1 is 1.3%/year. It is a not trascurable risk, but the indacation to oral anticoagulant therapy in this pt should be evaluated on the basis of clinical net benefit - balance of risks and benefits (anticoagulant therapy bleeding risk is 1.2%)

2013 AIAC Guideline for the Management of Patients With Atrial Fibrillation

Event rate(95%CI) of hospital

admission and death due to

thromboembolism per

100 person year

Kaplan-Meier estimate of probability of remaining free of thromboembolism with CHADS2 score 0 and 1

Kaplan-Meier estimate of probability of remaining free of thromboembolism with CHA2DS2-VASc score 0 and 1

ASA Conclusions

➢Antiplatelet therapy should be considered only when patients refuse any OAC, or cannot tolerate OAC for reasons unrelated to bleeding, or in a specific subgroups of pt with CHADVASC 1

➢In the real world, antiplatelet therapy is still commonly prescribed for stroke prevention in AF

➢Compared with ASA, NOAs (apixaban) significantly reduced the relative risk of stroke or systemic embolism by 55% while the risk of major bleeding was not significantly increased

➢The evidence demonstrated that oral anticoagulation should be the preferred option in NVAF patients at risk of stroke