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

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 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

Geregistreerde indicaties NOACs NOAC orthopedie AF VTE/PE post ACS CHZ en PAD dabigatran + + + - - rivaroxaban + + + + + apixaban + + + - - edoxaban - + + - - Farmaceutisch Kompas 2019

R OLE OF T HROMBIN IN C ORONARY C LOT F ORMATION Welsh RC. Am Heart J 2016;181:92-100

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 Falati et al . Nat Med 2002;8:1175–80.

F IRST R ANDOMIZED C ONTROLLED T RIAL OF W ARFARIN IN C ARDIAC D ISEASE Ann Intern Med 1949;30:80-91

Lan Lancet et 1980; 1980;ii:989 989-994 994 F IRST R ANDOMIZED P LACEBO -C ONTROLLED T RIAL OF W ARFARIN AFTER MI n = 878 878 Lancet 1980;ii:989-994

Aspirin vs Acenocoumarol vs Both after MI death, reMI, stroke mortality ASPECT-2. Lancet 2002:360:109-113

Aspirin vs Warfarin vs Both after MI n = 3,630 WARIS-2. N Engl J Med 2002; 347:969-974

NOAC plus aspirin vs aspirin alone after ACS: death, MI or stroke 14 12 HR = 0.66 (0.48 - 0.90), p < 0.02 11.1 10 8 7.4 6 4 placebo (n = 638) all doses ximelagatran (n = 1,245) 2 0 0 30 60 90 120 150 180 days after randomization ESTEEM. Lancet 2003;362:789-797

ATLAS-2 ACS ACS aspirin + clopidogrel day 4 at discharge placebo rivaroxaban 5 mg bid rivaroxaban 2.5 mg bid primary efficacy endpoint: death, MI, stroke primary safety endpoint: TIMI major bleeding N Engl J Med 2012;366:9-19

NOAC plus DAPT vs DAPT alone after ACS in ATLAS ACS-2: efficacy 12 Primary efficacy endpoint (CV death/MI/stroker 10.7% 10 Estimated cumulative rate (%) Placebo 8.9% 8 HR=0.84 Rivaroxaban (95% CI 0.74–0.96) 6 ARR=1.8% 4 mITT p =0.008 ITT p =0.002 2 NNT=56 0 24 0 3 6 9 12 15 18 21 Months after randomization N Engl J Med 2012;366:9-19

Low-dose NOAC plus DAPT vs DAPT alone after ACS in ATLAS ACS-2: efficacy CV death/MI/stroke (primary efficacy endpoint) Cardiovascular death All-cause death 13 5 5 HR=0.68 Placebo HR=0.84 HR=0.66 4.5% Placebo Placebo mITT p =0.02 mITT p =0.002 mITT p =0.002 4.1% 10.7% Cumulative incidence (%) ITT p =0.007 ITT p =0.005 ITT p =0.004 9.1% 2.9% 2.7% Rivaroxaban 2.5 mg bid Rivaroxaban Rivaroxaban 2.5 mg bid 2.5 mg bid NNT=63 NNT=71 NNT=63 0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 Months Months Months N Engl J Med 2012;366:9–19

NOAC plus DAPT vs DAPT alone after ACS in ATLAS ACS-2: bleeding ‡ ‡ Rivaroxaban Rivaroxaban # vs placebo vs placebo p =NS p =NS * (principal safety outcome) NNH = 575 * p =0.04 vs placebo; # p =0.005 vs placebo; ‡ p <0.001 vs placebo. N Engl J Med 2012;366:9-19

S TENT T HROMBOSIS WITH NOAC S AFTER ACS reported stent thrombosis (%) trial f/u (m) n NOAC placebo RR 95% CI) NNT 0.73 (0.47 - 1.12) * APPRAISE-2 8 7,392 0.9 1.3 250 ATLAS-2 1 0.69 (0.51 - 0.93) ** 13 15,526 2.3 2.9 250 1 both doses * p = 0.15 ** p = 0.02 Verheugt FWA. Eur Heart J 2013;34:1618-1620

N Engl J Med 2017;377:1319-1330

COMPASS: Primary Endpoint N Engl J Med 2017;377:1319-1330

COMPASS: Primary Endpoint N Engl J Med 2017;377:1319-1330

COMPASS: Secondary Endpoints NNT = 143 N Engl J Med 2017;377:1319-1330

COMPASS: Bleeding Endpoints NNH =83 N Engl J Med 2017;377:1319-1330

COMPASS: Net Clinical Benefit N Engl J Med 2017;377:1319-1330

COMPASS-CAD substudy (n = 24,824, or 91% of COMPASS total population) Lancet 2018;391:205-218

COMPASS CAD substudy: Primary endpoint (n = 24,824, 91% of COMPASS) Remote ACS: 69% Remote PCI: 60% Lancet 2018;391:205-218

Long-Term Aspirin-Controlled Studies on Dual Therapy Verheugt FWA. Circulation. 2018;137:1655-1657

Take-home messages Een nieuwe NOAC indicatie is gestabiliseerd acuut coronairsyndroom op 1. dubbele antiplaatjestherapie, maar deze benaderiing wordt weinig toegepast (triple antitrombotische therapie niet erg aantrekkelijk). 2. Een nieuwe en wel veelbelovende indicatie is secundaire preventie bij patiënten met chronisch coronairlijden en bij perifere vaatziekten, die alleen aspirine gebruiken.