Transfusion triggers in acute coronary syndromes: The MINT trial
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1 Transfusion triggers in acute coronary syndromes: The MINT trial Paul Hébert, MD MHSc(Epid) Physician-in-Chief, CHUM Professor, University of Montreal
2 Objectives Review evidence on transfusion triggers Describe upcoming studies on transfusion triggers No relevant competing interests
3 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: , 1999
4 Study Design 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 Hebert et al. NEJM 321: , 1999
5 Survival (%) Survival of all patients over 30 days Restrictive strategy 18.7% Liberal strategy 23.3% 60 p= Time (Days) Hebert et al. NEJM 321: , 1999
6 Complications Complication Liberal Restrictive P Values (n=420) (n=418) 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
7 Survival (%) Survival (%) Cardiovascular Disease Patients with cardiovascular diseases (n=357) Patients with ischemic heart disease (n=257) Liberal Restric tiv e 90 Liberal Restric tiv e p = p = Time (Days) Time (Days) Hebert et al. NEJM 321: , 1999
8 30-Day Mortality Carson JL, Stanworth, Hebert, et al. Cochrane Database of Systematic Reviews 2016
9 NEJM editorial title
10
11 Odds Ratio Effect of anemia on mortality in cardiac disease Healthy (No IHD) Ischemic Heart Disease P=0.03 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 Preoperative Hgb (g/dl) Carson JL, et al. Lancet 1996;348:
12 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
13 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, pp
14 Hospital Outcomes Carson JL et al. N Engl J Med 2011;365:
15 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)
16 MINT Pilot Trial Clinical Outcomes at 30 Days Death/MI/ Revascularization Liberal N=55 Restrictive N=54 6 (10.9%) 14 (25.9%) Death 1 (1.8%) 7 (13.0%) MI 5 (9.1%) 7 (13.0%) Revascularization 0 (0.0%) 2 (3.7%) Absolute risk difference (95% CI) 15.0% (0.7 to 29.3)* 11.2%** (1.5 to 20.8) 13.0% (-7.9 to15.6) 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
17 CRIT Trial Clinical Outcomes at 30 Days Liberal N=21 Restrictive N=24 P value Death, recurrent MI, CHF 13 (61.9%) 5 (20.1%) Death 1 (4.7%) 2 (8.3%) NS CHF 8 (38.1%) 2 (8.3%) 0.03 Cooper et al Am Heart Journal 2013
18 Restrictive Liberal
19 Murphy et al, NEJM 2015
20 Published on-line October 12, 2016
21 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
22 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
23 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
24 Thank you
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