Dataset Information

Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: Rationale and design of the REALITY trial.

ABSTRACT:

Background

Anemia is common in patients with acute myocardial infarction (AMI), and is an independent predictor of mortality. The optimal transfusion strategy in these patients is unclear.

Hypothesis

We hypothesized that a "restrictive" transfusion strategy (triggered by hemoglobin ?8?g/dL) is clinically noninferior to a "liberal" transfusion strategy (triggered by hemoglobin ?10?g/dL), but is less costly.

Methods

REALITY is an international, randomized, multicenter, open-label trial comparing a restrictive vs a liberal transfusion strategy in patients with AMI and anemia. The primary outcome is the incremental cost-effectiveness ratio (ICER) at 30?days, using the primary composite clinical outcome of major adverse cardiovascular events (MACE; comprising all-cause death, nonfatal stroke, nonfatal recurrent myocardial infarction, or emergency revascularization prompted by ischemia) as the effectiveness criterion. Secondary outcomes include the ICER at 1?year, and MACE (and its components) at 30?days and at 1?year.

Results

The trial aimed to enroll 630 patients. Based on estimated event rates of 11% in the restrictive group and 15% in the liberal group, this number will provide 80% power to demonstrate clinical noninferiority of the restrictive group, with a noninferiority margin corresponding to a relative risk equal to 1.25. The sample size will also provide 80% power to show the cost-effectiveness of the restrictive strategy at a threshold of €50?000 per quality-adjusted life year.

Conclusions

REALITY will provide important guidance on the management of patients with AMI and anemia.

SUBMITTER: Ducrocq G

PROVIDER: S-EPMC7852166 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: Rationale and design of the REALITY trial.

Ducrocq Gregory G Calvo Gonzalo G González-Juanatey José Ramón JR Durand-Zaleski Isabelle I Avendano-Sola Cristina C Puymirat Etienne E Lemesle Gilles G Arnaiz Joan Albert JA Martínez-Sellés Manuel M Rousseau Alexandra A Cachanado Marine M Vicaut Eric E Silvain Johanne J Karam Carma C Danchin Nicolas N Simon Tabassome T Steg Philippe Gabriel PG

Clinical cardiology 20210106 2

<h4>Background</h4>Anemia is common in patients with acute myocardial infarction (AMI), and is an independent predictor of mortality. The optimal transfusion strategy in these patients is unclear.<h4>Hypothesis</h4>We hypothesized that a "restrictive" transfusion strategy (triggered by hemoglobin ≤8 g/dL) is clinically noninferior to a "liberal" transfusion strategy (triggered by hemoglobin ≤10 g/dL), but is less costly.<h4>Methods</h4>REALITY is an international, randomized, multicenter, open-l ...[more]

PMID: 33405291

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Project description:BackgroundA strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level.MethodsIn this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days.ResultsA total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49).ConclusionsIn patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).

Project description:Objective: Anemia is frequent in patients with acute myocardial infarction (AMI), and the optimal red blood cell transfusion strategy for AMI patients with anemia is still controversial. We aimed to compare the efficacy of restrictive and liberal red cell transfusion strategies in AMI patients with anemia. Methods: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, and Clinicaltrials.gov, from their inception until March 2021. Studies designed to compare the efficacy between restrictive and liberal red blood cell transfusion strategies in patients with AMI were included. The primary outcome was all-cause mortality, including overall mortality, in-hospital or follow-up mortality. Risk ratios (RR) with 95% confidence intervals (CI) were presented and pooled by random-effects models. Results: The search yielded a total of 6,630 participants in six studies. A total of 2,008 patients received restrictive red blood cell transfusion while 4,622 patients were given liberal red blood cell transfusion. No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups (RR = 1.07, 95% CI = 0.82-1.40, P = 0.62; RR = 0.89, 95% CI = 0.56-1.42, P = 0.62). However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion (RR = 1.22, 95% CI = 1.00-1.50, P = 0.05). No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. In addition, subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design. Conclusion: Restrictive and liberal red blood cell transfusion have a similar effect on overall mortality and follow-up mortality in AMI patients with anemia. However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion. The findings suggest that transfusion strategy should be further evaluated in future studies.

Project description:ImportanceThe optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear.ObjectiveTo determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy.Design, setting, and participantsOpen-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019.InterventionsPatients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy.Main outcomes and measuresThe primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome.ResultsAmong 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups.Conclusions and relevanceAmong patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm.Trial registrationClinicalTrials.gov Identifier: NCT02648113.

Project description:ObjectiveTo compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.DesignSystematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data sourcesCochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.Trial selectionPublished and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.Data extractionTwo authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.Results31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference -1.43, 95% confidence interval -2.01 to -0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.ConclusionsCompared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.Trial registrationPROSPERO CRD42013004272.

Project description:BackgroundWe assessed the effect of liberal versus restrictive red blood cell transfusion strategy on survival outcome in sepsis or septic shock by systematically reviewing the literature and synthesizing evidence from randomized controlled trials (RCTs).MethodsWe searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases. We included RCTs that compared mortality between a liberal transfusion strategy with a hemoglobin threshold of 9 or 10 g/dL and a restrictive transfusion strategy with a hemoglobin threshold of 7 g/dL in adults with sepsis or septic shock. Two investigators independently screened citations and conducted data extraction. The primary outcome was 28- or 30-day mortality. Secondary outcomes were 60- and 90-day mortality, use of life support at 28 days of admission, and number of patients transfused during their intensive care unit stay. DerSimonian-Laird random-effects models were used to report pooled odds ratios (ORs).ResultsA total of 1516 patients from three RCTs were included; 749 were randomly assigned to the liberal transfusion group and 767 to the restrictive strategy group. Within 28-30 days, 273 patients (36.4%) died in the liberal transfusion group, while 278 (36.2%) died in the restrictive transfusion group (pooled OR, 0.99; 95% confidence interval [CI], 0.67-1.46). For the primary outcome, heterogeneity was observed among the studies (I2 = 61.0%, χ2 = 5.13, p = 0.08). For secondary outcomes, only two RCTs were included. There were no significant differences in secondary outcomes between the two groups.ConclusionsWe could not show any difference in 28- or 30-day mortality between the liberal and restrictive transfusion strategies in sepsis or septic shock patients by meta-analysis of RCTs. Our results should be interpreted with caution due to the existence of heterogeneity. As sepsis complicates a potentially wide range of underlying diseases, further trials in carefully selected populations are anticipated.Trial registrationThis present study was registered in the PROSPERO database (CRD42018108578).

Project description:BackgroundThere are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality.MethodsThis was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels.ResultsWe included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens.ConclusionsMeta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy.Trial registrationPROSPERO CRD42019120503.

Project description:BackgroundBone marrow failure disorders include a heterogenous group of disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup. MDS is predominantly a disease of the elderly, with many elderly people managed conservatively with regular allogeneic red blood cell (RBC) transfusions to treat their anaemia. However, RBC transfusions are not without risk. Despite regular transfusions playing a central role in treating such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear.ObjectivesTo assess the efficacy and safety of a restrictive versus liberal red blood cell transfusion strategy for patients with myelodysplasia, acquired aplastic anaemia, and other inherited bone marrow failure disorders.Search methodsWe searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (from 1946), Ovid EMBASE (from 1974), EBSCO CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 26th May 2015.Selection criteriaRCTs including patients with long-term bone marrow failure disorders that require allogeneic blood transfusion, who are not being actively treated with a haematopoietic stem cell transplant, or intensive chemotherapy.Data collection and analysisWe used standard Cochrane review methodology. One author initially screened all references, and excluded any that were clearly irrelevant or duplicates. Two authors then independently screened all abstracts of articles, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant articles for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool.Main resultsWe included one trial (13 participants) and identified three ongoing trials that assess RBC transfusion strategies in people with MDS.The quality of the evidence was very low across different outcomes according to GRADE methodology.The one included study randomised participants to a restrictive [haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient evidence to determine a difference in all-cause mortality (1 RCT; 13 participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was insufficient evidence to determine a difference in the number of red blood cell transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the liberal group, compared to 0.8 in the restrictive arm, no standard deviation was reported; very low quality evidence). There were no anaemia-related complications reported (cardiac failure) and no reported effect on activity levels (no statistics provided). The study did not report: mortality due to bleeding/infection/transfusion reactions or iron overload, quality of life, frequency and length of hospital admissions, serious infections (requiring admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or equivalent) or above).Authors' conclusionsThis review indicates that there is currently a lack of evidence for the recommendation of a particular transfusion strategy for bone marrow failure patients undergoing supportive treatment only. The one RCT included in this review was only published as an abstract and contained only 13 participants. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients, particularly as the incidence of the main group of bone marrow failure disorders, MDS, rises with an ageing population.

Dataset Information

Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: Rationale and design of the REALITY trial.

Background

Hypothesis

Methods

Results

Conclusions

Publications

Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: Rationale and design of the REALITY trial.

Similar Datasets

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