1) The REALITY trial compared a restrictive versus liberal red blood cell transfusion strategy in 630 patients with acute myocardial infarction and mild anemia. 2) The primary outcome of 30-day major adverse cardiovascular events was non-inferior for the restrictive strategy compared to the liberal strategy. 3) A cost-effectiveness analysis found the restrictive strategy had an 84% probability of being the dominant strategy by being both more effective and less costly.

1. REALITY - A Randomized Trial of Transfusion
Strategies in patients with Myocardial Infarction
and Anemia
30-day results
Ph.Gabriel Steg on behalf of the REALITY investigators
Hôpital Bichat, Assistance Publique – Hôpitaux de Paris,
Université de Paris, INSERM U-1148, Paris, France,
FACT: French Alliance for Cardiovascular clinical Trials
@gabrielsteg
Clinical Trials.gov registration number: NCT02648113.

2. Disclosures
• Ph.Gabriel Steg discloses
– Research grants : Bayer, Merck, Servier, Sanofi
– Speaker or consultant (including steering committee, DMC and CEC memberships) : Amarin,
Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, BristolMyersSquibb, Idorsia, Mylan,
NovoNordisk, Novartis, Pfizer, Regeneron, Sanofi, Servier
• Trial design : FACT ( French Alliance for Cardiovascular Trials)
• Trial sponsor: Assistance Publique – Hôpitaux de Paris
• Trial funded via
– a grant from Programme de Recherche Médico-Economique (PRME) 2015, from the
French Ministry of Health
– a grant from Instituto de Salud Carlos III (the Spanish Ministry of Economy and
Competitiveness), Grant nº PI15/01543.
• No commercial/industry support.

3. Rationale
• Anemia is frequent and impacts prognosis in patients with MI
• Blood is a precious resource, and transfusion is costly,
logistically cumbersome, and has side effects.
• There is uncertainty as to which transfusion strategy is best in
this population
• RCTs have compared a restrictive and a liberal transfusion
strategy in cardiac and non-cardiac surgery or in patients with
GI bleeding but have excluded patients with acute MI
3

4. 630 Pts with acute MI and 7 < Hb ≤ 10 g/dL at any time during admission
Primary Endpoints:
- Clinical: 30-day MACE (death, reinfarction, stroke, and emergency revascularization prompted by ischemia)
- Cost effectiveness: 30-day ICER
- Secondary endpoints: MACE at 1-year, Cost-utility at 30-days and 1-year
randomization
Liberal RBC transfusion
strategy
triggered by Hb  10 g/ dL
target Hb: > 11g / dL
Restrictive RBC transfusion
strategy
triggered by Hb  8g/ dL
target Hb: 8 to 10 g/dL
REALITY: a joint French/Spanish trial
The strategies should be maintained until discharge from hospital or for 30 days, whichever comes first
Tranfusion allowed at any time if: massive overt active bleeding; presumed important fall in Hb level and no time to wait
for Hb dosage, shock occurring after randomization.

5. Hb levels and transfusions
Restrictive strategy
n=342
Liberal strategy
n=324
p-value
Hb level
At admission 10.0 ± 1.7 10.1 ± 1.6 0.59
At randomization 9.0 ± 0.8 9.1 ± 0.8 0.17
Lowest value during hospital stay 8.3 ± 0.9 8.8 ± 0.9 <0.0001
At discharge 9.7 ± 1.0 11.1 ± 1.4 <0.0001
Red cell transfusion
Patients receiving at least 1 RBPC (n, %) 122 (35.7) 280 (86.7) <0.0001
Units transfused
Total 342 756
Mean/patient, sd 2.9 ± 3.7 2.8 ± 2.7
Major protocol violations1 (n, %) 14 (4.1) 2 (0.6)
D = 414

6. Primary Clinical Outcome*– Per Protocol Population
PP Restrictive strategy
n=327
n (%)
Liberal strategy
n=321
n (%)
Difference [95%CI]
Relative Risk
(Restrictive
vs. Liberal)
One sided
97.5%CI
MACE
36
11.0%
45
14.0% -3.0% [-8.4% ; 2.4%] 0.79 ]-inf ; 1.18]
0.75 1 1.25
0.79 1.18
The restrictive strategy is non-
inferior to the liberal strategy.
This was also verified in the ITT
population
Relative Risk
Non Inferiority margin
*MACE: all-cause death, reinfarction, stroke, and emergency revascularization prompted by ischemia

7. Safety endpoints
Restrictive strategy Liberal Strategy Difference
[95%CI]
p
At least one safety event (n, %)
40
11.7%
36
11.1%
0.5% [-4.5% ; 5.7%] 0.81
Acute renal failure (n, %)
33
9.7%
23
7.1%
2.6% [-2.0% ; 7.1%] 0.24
Severe allergic reaction (n, %)
3
0.9%
0
0
0.9% [-0.4% ; 2.2%] 0.25
Infection (n, %)
0
0.0%
5
1.5%
-1.5% [-3.2% ; 0.1%] 0.03
Hemolysis (n, %) 0 0 NC NC
Multiorgan system dysfunction (n, %)
1
0.3%
3
0.9%
-0.6% [-2.1% ; 0.9%] 0.36
Acute lung injury (n, %)
1
0.3%
7
2.2%
-1.9% [-3.9% ; 0.1%] 0.03
Acute heart failure (n, %)
11
3.2%
12
3.7%
-0.5% [-3.6% ; 2.6%] 0.73

8. Cost Effectiveness analysis
8
More effective
Less effective
Higher
Costs
Lower
costs
Delta effectiveness (MACE @ D30)
Delta
Cost
(€)
More expensive
Less effective
More expensive
More effective
Less expensive
Less effective
Less expensive
More effective
(dominant)
Bootstrapping was used to
quantify uncertainty
1,000 paired estimates of mean
differential costs and MACE

9. Cost Effectiveness analysis
The restrictive strategy has an 84% probability of being dominant
9
More effective
Less effective
Higher
Costs
Lower
costs
Delta effectiveness (MACE @ D30)
Delta
Cost
(€)
Strategy
Liberal
Restrictive
Bootstrapping was used
to quantify uncertainty
1,000 paired estimates of
mean differential costs
and MACE

10. Conclusions
• The restrictive transfusion strategy
– is non-inferior to a liberal strategy in preventing 30-day MACE
– saves blood,
– is safe.
• Cost effectiveness analysis indicated that the restrictive
strategy has a high probability of being cost-saving while being
outcome-improving (i.e. “dominant”).
• These observations support the use of the restrictive strategy