Transfusion triggers in acute

coronary syndromes:

The MINT trial

Paul Hébert, MD MHSc(Epid)

Physician-in-Chief, CHUM

Professor, University of Montreal

Objectives

• Review evidence on transfusion triggers

• Describe upcoming studies on transfusion

triggers

No relevant competing interests

Purpose:

Are a restrictive and liberal red cell transfusion strategy are equivalent in terms of effects on mortality and morbidity in critically ill patients

Hebert et al. NEJM 321: 151-156, 1999

Study design: Multicentre RCT

Setting: 25 ICUs across Canada

Study Population: Included Hb< 90 g/L within

72 hrs and excluded patients with active

blood loss (30 g/L decrease or >3 unit

transfusion in 12 hrs)

Intervention: 70 g/L vs 100 g/L hemoglobin

trigger

Outcomes: 30 day all-cause mortality and organ

failure

Study Design

Hebert et al. NEJM 321: 151-156, 1999

Survival of all patients

over 30 days

0 5 10 15 20 25 30

Time (Days)

50

60

70

80

90

100

Su

rviv

al (%

)

Restrictive strategy

Liberal strategy

p=0.10

Hebert et al. NEJM 321: 151-156, 1999

18.7%

23.3%

Complications

Complication Liberal (n=420)

Restrictive (n=418)

P Values

Cardiac No. (%) 88 (21.0) 55 (13.2) <0.01

Myocardial Infarction 12 (2.9) 3 (0.7) 0.02

Pulmonary Edema 45 (10.7) 22 (5.3) <0.01

Angina 9 (2.1) 5 (1.2) 0.28

Cardiac Arrest 33 (7.9) 29 (6.9) 0.6

Pulmonary No. (%) 122 (29.1) 106 (25.4) 0.22

ARDS 48 (11.4) 32 (7.7) 0.06

Pneumonia 86 (20.5) 87 (20.8) 0.92

0 5 10 15 20 25 30

Time (Days)

50

60

70

80

90

100

Su

rviv

al (%

)

p = 0.30

Liberal Restric tiv e

Cardiovascular Disease

Patients with ischemic heart

disease (n=257)

0 5 10 15 20 25 30

Time (Days)

50

60

70

80

90

100

Su

rviv

al (%

)

p = 0.95

Liberal Restric tiv e

Patients with cardiovascular

diseases (n=357)

Hebert et al. NEJM 321: 151-156, 1999

30-Day MortalityCarson JL, Stanworth, Hebert, et al. Cochrane Database of Systematic Reviews 2016

• NEJM editorial title

http://www.google.ca/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=QsICcVDTwuXThM&tbnid=QNiNo0Mnvj4xYM:&ved=0CAUQjRw&url=http%3A%2F%2Fsplash4ripples.com%2F2013%2F02%2F&ei=mK6DU9jgMsqxsQTVqID4Bg&bvm=bv.67720277,d.b2k&psig=AFQjCNFJhgDTXd2KogcrXj6XXx2OJP5kVw&ust=1401224975752913

Effect of anemia on mortality in cardiac disease

1

4

7

10

13

16

6 7 8 9 10 11 12+Preoperative Hgb (g/dl)

Od

ds R

atio

Healthy (No IHD)

Ischemic Heart Disease

P=0.03

Carson JL, et al. Lancet 1996;348:1055-60.

• Retrospective cohort of patients who refuse

blood transfusion

• CVD definition - History of MI, angina, CHF,

or PVD.

• 1,958 patients age 18 or older.

• Undergo surgical procedure in OR.

• Outcome-30-day mortality or morbidity.

Hebert and Fergusson,JAMA, 2004

How do Rao and Wu studies compare?

•Both studies document harm from RBC transfusion with hematocrits

exceeding 33%

•Reasons for differences at hematocrits< 33%

•Different population (younger and aggressively treated in Rao study)

•Different data acquisition Primary data collection vs administrative database

•Different statistical techniques

•Different event rates

Functional outcomes in cardiovascular patients

undergoing surgical hip fracture repair (FOCUS)

Design: Multicentre RCT in 47 North American centres

Study Population: 2016 hip fracture patients undergoing

surgical repair with a Hb < 100 g/L within 3 days fo surgery

Intervention:

• Liberal Strategy: transfusion trigger of 100 g/L

• Restrictive Strategy: transfusion for symptomatic anemia

Outcomes:

• Primary: functional recovery (ability to walk 10 feet without

human assistance 60 days post-op)

• Long term survival, nursing home placement, post-op

complications (MI and infection)

Carson et al. NEJM 2011, pp2453-62.

Hospital Outcomes

Carson JL et al. N Engl J Med 2011;365:2453-2462

Transfusion Threshold Trials in

Acute MI• 144 patients enrolled in two small trials

• 9 deaths in 78 patients in Restrictive

Group

• 2 deaths in 76 patients in Liberal Group

• Risk ratio=3.88 (95% CI, 0.83 to 18.13)

MINT Pilot Trial

Clinical Outcomes at 30 Days

LiberalN=55

RestrictiveN=54

Absolute risk difference (95% CI)

Death/MI/Revascularization

6 (10.9%) 14 (25.9%)15.0%(0.7 to 29.3)*

Death 1 (1.8%) 7 (13.0%)11.2%**(1.5 to 20.8)

MI 5 (9.1%) 7 (13.0%)13.0%(-7.9 to15.6)

Revascularization 0 (0.0%) 2 (3.7%)3.7%(-1.3 to 8.7)

*p=0.054, adjusted for age p=0.076 **p=0.032

Carson et al Am Heart Journal 2013

CRIT Trial

Clinical Outcomes at 30 Days

LiberalN=21

RestrictiveN=24

P value

Death, recurrent MI, CHF

13 (61.9%) 5 (20.1%) 0.046

Death 1 (4.7%) 2 (8.3%) NS

CHF 8 (38.1%) 2 (8.3%) 0.03

Cooper et al Am Heart Journal 2013

LiberalRestrictive

Murphy et al, NEJM 2015

Published on-line October 12, 2016

2016 AABB Transfusion Guidelines

• Restrictive transfusion 7 to 8 g/dL in most

patients

• No recommendation made in acute

coronary syndrome where the evidence is

judged to be insufficient for any

recommendation

• Need trials in patients with acute MI

Myocardial Ischemia and Transfusion Trial

Design: Multicentre RCT in 70 North American centres

Study Population: 3500 patients with either ST or nonST MI

(consistent with 3rd Universal definition) with Hb < 100 g/L

Intervention:

• Liberal Strategy: transfusion trigger of 100 g/L

• Restrictive Strategy: transfusion permitted if hemoglobin

concentration falls below 80 g/L and strongly recommended

below 70 g/L.

• transfusion for symptomatic anemia

Outcomes:

• All cause mortality and non-fatal re-infarction within 30 days

Take home messages

• In most ICU patients, a threshold of 70 g/L

should be the new normal

• In cardiac surgery, await results of TRICS III

• In acute coronary syndrome, unknown but 80

g/L seems reasonable

Join the MINT trial

Thank you