Uitbreiding indicaties NOACs: de stand van zaken Freek W.A. Verheugt - - PowerPoint PPT Presentation

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Dec 27, 2022 133 likes •407 views

Uitbreiding indicaties NOACs: de stand van zaken Freek W.A. Verheugt Amsterdam Disclosures for Freek W. A. Verheugt Research support/ Bayer HealthCare, Boehringer Ingelheim, Eli Lilly and Roche principal investigator Consultant Bayer

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Freek W.A. Verheugt

Amsterdam

Uitbreiding indicaties NOACs: de stand van zaken

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Research support/ principal investigator Bayer HealthCare, Boehringer Ingelheim, Eli Lilly and Roche Consultant Bayer Healthcare, Eli Lilly, Daiichi-Sankyo, and Merck Speakers’ bureau none Honoraria Bayer Healthcare, Eli Lilly, Daiichi-Sankyo and Merck DSMBs ENVISAGE TAVI-AF, ENTRUST AF-PCI, FRAIL

Disclosures for Freek W. A. Verheugt

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dabigatran rivaroxaban apixaban edoxaban

rthopedie

AF CHZ en PAD VTE/PE post ACS

+ +

+
NOAC

+ + + + + + +

+
+
+
Geregistreerde indicaties NOACs

Farmaceutisch Kompas 2019

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ROLE OF THROMBIN IN CORONARY CLOT FORMATION

Welsh RC. Am Heart J 2016;181:92-100

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Falati et al. Nat Med 2002;8:1175–80.

In vivo arterial thrombosis involves platelet aggregation, tissue factor generation and fibrin formation

Real-time in vivo imaging of arterial thrombus formation in the mouse after laser-induced vascular injury The video shows platelet deposition, tissue factor accumulation and subsequent fibrin generation at the injury site in the first minute after injury

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Ann Intern Med 1949;30:80-91

FIRST RANDOMIZED CONTROLLED TRIAL OF WARFARIN IN CARDIAC DISEASE

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Lan Lancet et 1980; 1980;ii:989 989-994 994

n = 878 878

FIRST RANDOMIZED PLACEBO-CONTROLLED TRIAL OF WARFARIN AFTER MI

Lancet 1980;ii:989-994

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death, reMI, stroke mortality

ASPECT-2. Lancet 2002:360:109-113

Aspirin vs Acenocoumarol vs Both after MI

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WARIS-2. N Engl J Med 2002; 347:969-974

n = 3,630

Aspirin vs Warfarin vs Both after MI

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NOAC plus aspirin vs aspirin alone after ACS: death, MI or stroke

2 4 6 8 10 12 14 30 60 90 120 150 180

days after randomization

7.4 11.1 HR = 0.66 (0.48 - 0.90), p < 0.02

placebo (n = 638) all doses ximelagatran (n = 1,245)

ESTEEM. Lancet 2003;362:789-797

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ATLAS-2 ACS

ACS aspirin + clopidogrel at discharge rivaroxaban 5 mg bid rivaroxaban 2.5 mg bid placebo

day 4

primary efficacy endpoint: death, MI, stroke primary safety endpoint: TIMI major bleeding

N Engl J Med 2012;366:9-19

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NOAC plus DAPT vs DAPT alone after ACS in ATLAS ACS-2: efficacy

Months after randomization HR=0.84 (95% CI 0.74–0.96) ARR=1.8% mITT p=0.008 ITT p=0.002 NNT=56 10.7% 8.9% Estimated cumulative rate (%) Rivaroxaban Placebo 12 15 10 8 6 4 2 21 12 9 3 24 Primary efficacy endpoint (CV death/MI/stroker 6 18 N Engl J Med 2012;366:9-19

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Cardiovascular death All-cause death CV death/MI/stroke (primary efficacy endpoint)

5 13

Months NNT=71

4.1% 2.7% Placebo Rivaroxaban 2.5 mg bid HR=0.66 mITT p=0.002 ITT p=0.005

18 12 6 5

Months 4.5% 2.9%

Placebo Rivaroxaban 2.5 mg bid HR=0.68 mITT p=0.002 ITT p=0.004

18 12 6

NNT=63 Months Cumulative incidence (%) HR=0.84 mITT p=0.02 ITT p=0.007 10.7% 9.1% Rivaroxaban 2.5 mg bid Placebo

24 18 12 6

NNT=63 N Engl J Med 2012;366:9–19

Low-dose NOAC plus DAPT vs DAPT alone after ACS in ATLAS ACS-2: efficacy

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*p=0.04 vs placebo; #p=0.005 vs placebo; ‡p<0.001 vs placebo. N Engl J Med 2012;366:9-19

Rivaroxaban vs placebo p=NS Rivaroxaban vs placebo p=NS

# ‡ ‡

(principal safety outcome)

NNH = 575

NOAC plus DAPT vs DAPT alone after ACS in ATLAS ACS-2: bleeding

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trial f/u (m) NOAC placebo NNT APPRAISE-2 8 0.9 1.3 250 ATLAS-21 13 2.3 2.9 250 stent thrombosis (%) n 7,392 15,526 RR 95% CI) 0.73 (0.47 - 1.12)* 0.69 (0.51 - 0.93)**

STENT THROMBOSIS WITH NOACS AFTER ACS

reported

1 both doses *

p = 0.15

** p = 0.02

Verheugt FWA. Eur Heart J 2013;34:1618-1620

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