Clinical trial NCT02648113: Cost-effectiveness and Cost-utility of Liberal vs Restrictive Red Blood Cell Transfusion Strategies in Patients With Acute Myocardial Infarction and Anaemia.
Official title: Cost-effectiveness and Cost-utility of Liberal vs Restrictive Red Blood Cell Transfusion Strategies in Patients With Acute Myocardial Infarction and Anaemia. The REALITY (REstrictive And LIberal Transfusion Strategies in Patients With Acute mYocardial Infarction) Randomized Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myocardial Infarction
Anemia
Blood Transfusion
Keywords: Myocardial Infarction
Anemia
Blood Transfusion
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2016-01-06
Enrollment: 668
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Anemia in patients with myocardial infarction (MI) is a relatively frequent issue, resulting in poorer outcome. There is equipoise regarding which transfusion strategy is best, and there is an international consensus on the urgent need for a randomized trial.

The investigators hypothesize that a "restrictive" transfusion strategy is at least non-inferior to a "liberal" transfusion strategy on 30-day outcomes of MI patients with anemia. Given the costs and risks of transfusion, a cost-effectiveness and cost-utility analysis becomes key to determining the role of each strategy.

Detailed description: Anemia is frequent in patients with myocardial infarction (MI). The antiplatelet and anticoagulant agents used for MI treatment increase the risk of bleeding, which in turn increases the risk of ischemia and mortality. Anemia is an independent predictor of cardiac events in this setting. In the "FAST-MI 2010" nationwide registry, the prevalence of anemia (defined as Hb \<10g/dL) at admission was 3% and impacted mortality. Whether this risk can be overcome by transfusion is debated.

In theory, transfusion should increase oxygen delivery to the myocardium. However, recent data suggest that oxygen delivery is not increased in patients receiving transfusion, that red blood cells are rapidly depleted of nitric oxide during storage and that, conversely, transfusion may increase platelet activation and aggregation and these consequences appear potentially even more deleterious in patients with cardiovascular disease. In the general population without cardiovascular disease of medical and surgical patients, the role of liberal vs restrictive transfusion strategies has been explored by a series of randomized trials, which have led to a consensus to withhold blood transfusions until a threshold of 7 to 8 g/dl hemoglobin is reached.

Among patients with myocardial infarction, however, both the deleterious consequences of anemia and the risks of transfusion may be greater, which leads to lingering uncertainty regarding the role of liberal vs restrictive transfusion strategies in this setting. The clinical data are observational and contradictory. Conversely, a large meta-analysis (\>200 000 patients) reported a higher risk of mortality and recurrent MI in MI patients who received transfusion. More recently, a careful observational study has shown that the majority of patients undergoing blood transfusion cannot be matched with non-transfused patients due to their markedly different clinical profiles, indicating that observational studies cannot reliable establish the benefits or risks of transfusion because they are hopelessly influenced by selection bias. These results strongly highlight the need for randomized trials to establish the role of transfusion during acute MI, a call for a randomized trial that has been echoed by several thought leaders in the field in recent years. Two small randomized trials (respectively 45 and 110 patients) comparing liberal vs. restrictive transfusion strategies in MI showed no clear difference in clinical outcomes but were both underpowered.

The only guideline regarding management of anemia in this setting is from the European Society of Cardiology (ESC) guidelines on non-ST segment elevation - acute coronary syndrome (NSTE-ACS), which advise blood transfusion only if the hemodynamic status is compromised or the hemoglobin level is \<7g/dL. As a result, there is wide variation in clinical practice. There is therefore equipoise regarding which transfusion strategy is best.

Hypothesis:

We hypothesize that a "restrictive" transfusion strategy (triggered by Hb \<= 8 g/ dL) will be clinically non-inferior to a "liberal" transfusion strategy (triggered by Hb \<= 10g/ dL) but will be less costly.

Main objective:

The main objective of the study is to compare cost-effectiveness of restrictive (triggered by Hb \<= 8 g/ dL) vs liberal (triggered by Hb \<= 10g/ dL) red blood transfusion strategies for patients with acute MI and anemia (7g /dL \< Hb \<= 10g / dL).

Secondary objective(s):

1. The key secondary objective is to perform cost-utility analyses at 30-days and 1 year.
2. The main clinical objective will be to determine whether a restrictive transfusion strategy is clinically non-inferior to a liberal transfusion strategy in terms of major adverse cardiac events (MACE) at 30 days, defined as the composite of all-cause death, nonfatal stroke, nonfatal recurrent MI, and emergency revascularization prompted by ischemia.

2. A tertiary objective will be to compare major adverse cardiac events (MACE) at 1 year, since the impact of transfusion strategies on MACE may be delayed, or conversely, an initial benefit of either strategy may become lost over the first year.

Eligibility criteria: Inclusion Criteria:

* Aged ≥ 18 years
* Recent acute myocardial infarction, with or without ST- segment elevation, with a combination of ischemic symptoms occurring in the past 48 hours,before the MI related admission, and elevation of biomarkers of myocardial injury (troponin)
* Anemia Hb ≤ 10g / dL but \> 7 g/dL on Hb, measured at any time during the index hospital admission for MI.
* Written informed consent
* Coverage for medical insurance.

Exclusion Criteria:

* Shock (SBP \< 90 mmHg with clinical signs of low output or patients requiring inotropic agents)
* MI occurring post-percutaneous coronary intervention (PCI) or post-coronary artery bypass graft (CABG) (i.e. type IV or V Acute MI according to the 2012 Universal Definition of MI
* Life-threatening or massive ongoing bleeding (as judged by the investigator)
* Any blood transfusion in the previous 30-days
* any known malignant hematologic disease Note: Sickle cell disease, thalassemia and anemia due to chronic renal failure (even under EPO) are not an exclusion criteria

Primary outcomes:
measure: Cost-effectiveness ratio at 30 days
timeFrame: 30 days
Secondary outcomes:
measure: Cost-effectiveness ratio at 1 year
timeFrame: 1 year
measure: Clinically non inferiority at 30 days
timeFrame: 30 days
measure: Clinically non inferiority at 1 year
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Philippe-Gabriel STEG
role: PRINCIPAL_INVESTIGATOR
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