Oral anticoagulant agent-associated bleeding events reporting system - - PowerPoint PPT Presentation

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Oral anticoagulant agent-associated bleeding events reporting system - - PowerPoint PPT Presentation

Jan 19, 2023 289 likes •620 views

Oral anticoagulant agent-associated bleeding events reporting system (ORANGE study) Laura Green 1,2,3 , Joan Morris 1 , Raza Alikhan 4 , Nicola Curry 5 , Rhona Maclean 6 , Khalid Saja 7 , Simon Stanworth 3,5 , Campbell Tait 8 , Joachim Tan 1 ,

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SLIDE 1

Oral anticoagulant agent-associated bleeding events reporting system (ORANGE study)

Laura Green1,2,3, Joan Morris1, Raza Alikhan4, Nicola Curry5, Rhona Maclean6, Khalid Saja7, Simon Stanworth3,5, Campbell Tait8, Joachim Tan1, Peter MacCallum1,2

1Barts and the London School of Medicine and Dentistry, Queen Mary University of London; 2Barts Health NHS Trust; 3NHS Blood and Transplant; 4University Hospital of Wales, Cardiff and Vale University Health Board; 5Oxford

University Hospitals NHS Trust; 6Sheffield Teaching Hospitals NHS Foundation Trust; 7Barking, Havering and Redbridge University Hospitals NHS Trust; 8Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde

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SLIDE 2

Summary

  • Background
  • Study Objectives
  • Study progress
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SLIDE 3

Background

NICE Commissioning Guide (2013) extrapolated to UK

  • Prevalence of AF about 2% of adult population of UK
  • Currently ≈ 500,000 on oral a/c therapy
  • Likely to increase towards 1 million with new initiatives
  • Reflects efficacy of warfarin and NOACs in stroke

prevention (2/3 reduction)

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SLIDE 4

Background

  • New cases of VTE ≈ 100,000 per year in UK
  • Additional 0.1% of adult population - 50,000 - need

long-term oral a/c therapy

  • Prosthetic heart valves 100,000
  • Other indications 100,000
  • Total 2.4% of adult population
  • ≈ 1.2 million people on oral a/c therapy
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SLIDE 5

Overview of anticoagulant therapy properties

Laura Green

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SLIDE 6

Safety

  • Budnitz et al (NEJM 2011)

– 100, 000 emergency admissions for adverse drug events in adults ≥ 65 years (2007-9) – 50% in adults ≥ 80 years

  • Warfarin 33%
  • Insulin 14%
  • Antiplatelet agents 13%
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SLIDE 7

Safety

  • Bleeding

– Major bleeding 1-3% per year – If 1.2 million people on oral a/c therapy

  • ≈24,000 major bleeds per year in UK
  • ≈ 500 per week, 2 or 3 per week per

acute Trust

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SLIDE 8

Safety

  • Warfarin-related bleeds

– management guidelines so must be ok?? – how good are we at managing warfarin- or NOAC- related bleeds??

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SLIDE 9

Correction of warfarin-associated major bleeding

(Toth et al; Blood Transf 2013)

  • Retrospective audit of emergency warfarin reversal
  • 131 consecutive patients
  • Median PCC dose 26.8 IU/kg, INR reduced 3.1 to 1.2
  • Vitamin K (5 mg) given in 91.6%
  • Median time from presentation to

– INR result 2.0 h (1.3 h in ICH) – Vit K administration 3.6 h (2.7 h in ICH) – PCC administration 5.2 h (3.0 h in ICH)

  • Mortality 7.6% (ICH 22.8%)
  • Thrombosis by 7 days 1.5%
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SLIDE 10

Meta-analysis of bleeding on NOACs

Chai-Adisaksopha et al. Blood 2014;124:2450-8

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SLIDE 11

Meta-analysis of bleeding on NOACs

Chai-Adisaksopha et al. Blood 2014;124:2450-8 Intracranial bleeds

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SLIDE 12

Meta-analysis of bleeding on NOACs

Chai-Adisaksopha et al. Blood 2014;124:2450-8 Fatal bleeds

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SLIDE 13

30-day mortality after major bleeding Dabigatran v warfarin

(Majeed et al Circulation 2013;128:2325-32)

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SLIDE 14

Management of major bleeding dabigatran v warfarin

(Majeed et al Circulation 2013;128:2325-32)

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SLIDE 15

Mortality in warfarin-related major bleeding – PCC v FFP Johansen M et al. Cochrane Review 2015

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SLIDE 16

Safety in clinical practice

Outcomes of major bleeding

Dresden NOAC registry (Bayer-Westendorf J et al. Blood 2014;124:955-62)

  • 1776 patients (67.5% AF; 32.5% VTE)
  • Major bleeding per 100 py – 3.1% AF; 4.1% VTE
  • 1082 all bleeds – 59% minor, 35% clinically relevant, 6% major
  • 66 major bleeds – 25 (38%) procedural intervention
  • 6 PCC – 5 showed stabilisation, 1 death from ICH with

delayed and underdosed PCC

  • Bleeding mortality at 90 days after major bleed 5.1%

– (15-20% for VKA in literature)

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SLIDE 17

ORANGE study Design

  • Prospective, multicentre, observational 3-year study
  • Collect data on the current management and outcomes
  • f patients who develop major bleeding while on OAC
  • warfarin, rivaroxaban, dabigatran, apixaban and
  • thers (as they become available)

Primary Objectives

  • Proportion of patients who develop major bleeding and:
  • present with ICH
  • die within 30 days of presentation
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SLIDE 18

Secondary Objectives

Estimate the effectiveness of products (PCC, rFVIIa or FEIBA, FgC) in treating major bleeding Characterise coagulation abnormalities of major bleeding associated with the new OAC Examine associations between clinical outcomes and:

  • transfusion requirements (RBC to FFP ratio)
  • correction of coagulation abnormalities resulting from

blood transfusion and/or other products

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SLIDE 19

ORANGE study

  • Major bleeding

– Bleeding leading to hospital admission and resulting in

  • Death
  • Transfusion of ≥ 2 units red cells
  • Transfusion of FFP
  • Administration of other products (PCC, rFVIIa, FEIBA, fibrinogen)
  • Bleeding into a critical organ
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SLIDE 20

Milestones

REC approval obtained (REC reference: 12/EE/0431) NIHR CRN Portfolio adopted (UKCRN ID: 15322) Recruitment began: October 2013 Study ends: December 2016 Number of sites: 31 recruiting; 2 pending R&D Quarterly newsletter Yearly reporting of results at BSH meetings

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SLIDE 21

Demographics

1059 cases have been reported between October 2013 and August 2015

Characteristics

N = 1059 Female / Male 520/539 Median age (yrs) 79 [IQR 70-85]

N (%)

Warfarin (Vitamin K antagonists) 909 (85.8) NOAC 150 (14.2)

  • Rivaroxaban

106 (10.0)

  • Apixaban

24 (2.3)

  • Dabigatran

20 (1.9)

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SLIDE 22

Indications for OAC

(% of total indications, not patients)

AF 59% Stroke 5% Other 5% PE 10% DVT 11% Heart valve 10%

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SLIDE 23

Age distribution by gender

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SLIDE 24

Site of bleeding by OAC type

Warfarin/VKA N = 909 NOAC N = 150 % Intracranial 43.0 28.7 Gastrointestinal 29.8 46.7 Other 27.2 24.6

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SLIDE 25

Hb (g/dL)

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SLIDE 26

INR

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SLIDE 27

Management of Bleeding 1

Intervention Number Vitamin K 269 Dose 5 mg 86 Route IV 254 10 mg 145 Oral 8 Other 26

unspec.

7

unspec.

12 Tranexamic acid 25 Haemodialysis 3 Surgery/Procedure 63 Neuro-surgical intervention 19 GI tract endoscopic investigation/procedure 23 Other 18

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SLIDE 28

Management of Bleeding 2

PCC, FEIBA

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SLIDE 29

Management of Bleeding 3

RBC, FFP, Platelets & Cryoprecipitate

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SLIDE 30

Outcomes at 30 days

Discharged 62.2% Still inpatient 12.5% Died 19.8% Pending 5.5% % Discharged Inpatient Died Report pending* VKA (n= 909) 62.7 12.4 19.8 5.1 NOAC (n=150) 59.3 12.7 20.0 8.0 Overall (n=1059) 62.2 12.5 19.8 5.5

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SLIDE 31

Length of hospitalisation

(for discharged patients)

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SLIDE 32

Summary

  • 85.8% warfarin; 14.2% NOAC.
  • Median age: 79 yrs
  • 41% ICH; 32.2% G-I bleeds overall, however:
  • Rate of ICH is higher with VKA than NOAC
  • Rate of G-I bleed is higher with NOAC than VKA
  • Overall mortality rate at 30 days is 19.8%.