Impact of restrictive red blood cell transfusion strategy on thrombosis-related events: A meta-analysis and systematic review
Vox sanguinis. 2022
BACKGROUND AND OBJECTIVES There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. MATERIALS AND METHODS We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. RESULTS Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p = 0.020; I(2) = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64-1.09; p = 0.180; I(2) = 0.0%, very low-quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87-1.26; p = 0.620; I(2) = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups). CONCLUSIONS A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.
Adult patients in any clinical setting (30 studies, n= 17,334).
Restrictive red blood cell transfusion.
Liberal red blood cell transfusion.
The pooled risk ratio (RR) for thromboembolic events was 0.65 (very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR= 0.83, very low-quality evidence) or myocardial infarction (RR= 1.05, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced thromboembolic events in trials conducted in North America, and myocardial infarctions in the subgroup of trials where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups).
Transfusion strategies in patients with acute coronary syndrome and anemia: a meta-analysis
The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology. 2022;74(1):17
BACKGROUND Anemia is a known risk factor for ischemic heart disease and serves as an independent predictor of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This meta-analysis pools data from randomized controlled trials (RCTs) to better define hemoglobin (Hb) thresholds for transfusion in this setting. RESULTS MEDLINE, EMBASE, and Cochrane databases were searched using the terms "Acute Coronary Syndrome" AND "Blood Transfusion" including their synonyms. A total of three randomized controlled trials were included. Restrictive transfusion strategy (RTS) was defined as transfusing for Hb ≤ 8 g/dl with a post-transfusion goal of 8 to 10 g/dl. Liberal transfusion strategy (LTS) was defined as Hb ≤ 10 g/dl and post-transfusion goal of at least 11 g/dl. The primary end point was 30-day mortality. Secondary outcomes included recurrent ACS events, new or worsening CHF within 30 days, and major adverse cardiac events (MACE). The primary analytic method used was random effects model. Out of 821 patients, 400 were randomized to LTS, and 421 to RTS. Mean age was 70.3 years in RTS versus 76.4 in LTS. There was no statistically significant difference for 30-day mortality in LTS compared to RTS [odds ratio (OR) 1.69; 95% CI 0.35 to 8.05]. Similarly, there was no difference in MACE (OR 0.74; 95% CI 0.21 to 2.63), CHF (OR 0.82; 95% CI 0.18 to 3.76), or the incidence of recurrent ACS (OR 1.21; 95% CI 0.49 to 2.95). CONCLUSIONS In the setting of ACS, there is no difference between LTS and RTS for the outcomes of mortality, MACE, recurrent ACS, or CHF at 30 days. Further evidence in the form of high-quality RCTs are needed to compare RTS and LTS.
Restrictive vs. Liberal Red Blood Cell Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: A Systematic Review and Meta-Analysis
Frontiers in cardiovascular medicine. 2021;8:736163
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.
Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial
IMPORTANCE The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear. OBJECTIVE To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy. DESIGN, SETTING, AND PARTICIPANTS Open-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. INTERVENTIONS Patients 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 MEASURES The 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. RESULTS Among 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 RELEVANCE Among 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 REGISTRATION ClinicalTrials.gov Identifier: NCT02648113.
Patients with myocardial infarction enrolled in the REALITY trial (n= 668).
Restrictive transfusion strategy, haemoglobin <8 g/dL (n= 342).
Liberal transfusion strategy, haemoglobin <10 g/dL (n = 324).
Among the patients in the restrictive transfusion group, 122 (35.7%) received transfusion, compared to 323 (99.7%) patients in the liberal transfusion group. At 30 days, major adverse cardiovascular events occurred in 36 patients (11.0%) in the restrictive group and in 45 patients (14.0%) in the liberal group. 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.
Risks of restrictive red blood cell transfusion strategies in patients with cardiovascular disease (CVD): a meta-analysis
Transfusion Medicine (Oxford, England). 2018;28((5):):335-345.
AIM: To evaluate the risks of restrictive red blood cell transfusion strategies (haemoglobin 7-8 g dL(-1) ) in patients with and without known cardiovascular disease (CVD). BACKGROUND Recent guidelines recommend restrictive strategies for CVD patients hospitalised for non-CVD indications, patients without known CVD and patients hospitalised for CVD corrective procedures. METHODS/MATERIALS Database searches were conducted through December 2017 for randomised clinical trials that enrolled patients with and without known CVD, hospitalised either for CVD-corrective procedures or non-cardiac indications, comparing effects of liberal with restrictive strategies on major adverse coronary events (MACE) and death. RESULTS In CVD patients not undergoing cardiac interventions, a liberal strategy decreased (P = 0.01) the relative risk (95% CI) (RR) of MACE [0.50 (0.29-0.86)] (I(2) = 0%). Among patients without known CVD, the incidence of MACE was lower (1.7 vs 3.9%), and the effect of a liberal strategy on MACE [0.79, (0.39-1.58)] was smaller and non-significant but not different from CVD patients (P = 0.30). Combining all CVD and non-CVD patients, a liberal strategy decreased MACE [0.59, (0.39-0.91); P = 0.02]. Conversely, among studies reporting mortality, a liberal strategy decreased mortality in CVD patients (11.7% vs.13.3%) but increased mortality (19.2% vs 18.0%) in patients without known CVD [interaction P = 0.05; ratio of RR 0.73, (0.53-1.00)]. A liberal strategy also did not benefit patients undergoing cardiac surgery; data were insufficient for percutaneous cardiac procedures. CONCLUSIONS In patients hospitalised for non-cardiac indications, liberal transfusion strategies are associated with a decreased risk of MACE in both those with and without known CVD. However, this only provides a survival benefit to CVD patients not admitted for CVD-corrective procedures.
Red blood cell transfusion in patients with ST-elevation myocardial infarction-a meta-analysis of more than 21,000 patients
Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2018;26((9):):454-460
BACKGROUND Red blood cell transfusion remains controversial in patients with acute coronary syndromes and particularly in patients with ST-elevation myocardial infarction (STEMI). METHODS We systematically searched PubMed, Cochrane, EMBASE, and Web of Science for studies published until January 2017 describing the outcomes in patients with STEMI who received red blood cell transfusion, compared with patients who did not. RESULTS A total of 21,770 patients with STEMI from 5 cohort studies were included in the meta-analysis, 984 (4.5%) received red blood cell transfusion and 20,786 (95.4%) did not. Red blood cell transfusion was associated with a higher risk of in-hospital and long-term mortality, emergency repeated percutaneous coronary intervention (PCI), reinfarction rate, stroke rate, and heart failure. The group with red blood cell transfusion had a slightly higher incidence of diabetes mellitus and hypertension, but a lower incidence of smoking. The two groups had the same incidence of prior myocardial infarction, prior coronary artery bypass graft surgery and malignancy. Prior heart failure, prior stroke and prior PCI were more frequent in the group that had received red blood cell transfusion. The mean nadir haemoglobin was 8.5+/- 0.1g/dl in the group with red blood cell transfusion and 12.5+/- 0.4g/dl in the control group, p< 0.001. CONCLUSIONS Red blood cell transfusion increases the morbidity and mortality in patients with STEMI. This difference could not be explained by the higher morbidity in the red blood cell transfusion group alone. Further randomised controlled trials are required to provide a reliable haemoglobin threshold for these patients.
Impact of red blood cell transfusion on acute coronary syndrome: a meta-analysis
Internal & Emergency Medicine. 13(2):231-241, 2018 03.. 2018;13((2):):231-241
The impact of red blood cell transfusion on outcomes in patients with acute coronary syndrome is controversial. Pubmed, EMBASE, and Cochrane Library were searched for studies of red blood cell transfusion and acute coronary syndrome that were published in any language, from January 1, 1966, to April 1, 2016. We analyzed 17 observational studies, of 2,525,550 subjects. We conducted a systematic review with meta-analysis of studies assessing the association between blood transfusion and the risk for all-cause mortality and reinfarction. The search yielded 17 observational studies, of 2,525,550 subjects, during a study follow-up period, ranging from 30 days to 5 years. Red blood cell transfusion compared with no blood transfusion is associated with higher short- and long-term all-cause mortality as well as reinfarction rates (adjusted RR 2.23; 95% CI 1.47-3.39; HR 1.93; 95% CI 1.12-3.34; RR 2.61; 95% CI 2.17-3.14, respectively). In hemoglobin-stratified analyses, a graded association between red blood cell transfusion and mortality was observed, transfusion and risk of all-cause mortality was borderline significant at hemoglobin levels below 8.0 g/dL (RR 0.52; 95% CI 0.25-1.06), and was associated with an increased risk of mortality at a hemoglobin above 10 g/dL (RR 3.34; 95% CI 2.25-4.97). Red blood cell transfusion was associated with an increased risk of short- and long-term mortality as well as myocardial reinfarction. However, transfusion appeared to have beneficial or neutral effects on mortality at hemoglobin levels below 8.0 g/dL, and harmful effects above 10 g/dL. A large definitive randomized controlled trial addressing this issue is urgently required.
Blood transfusion and mortality in myocardial infarction: an updated meta-analysis
Background: Several observational and preclinical studies have shown that blood transfusion may modify the mortality of patients with myocardial infarction (MI). The aim of this meta-analysis is to evaluate the recent evidence on the effectiveness of blood transfusion for all-cause mortality in patients with MI. Materials and Methods: PUBMED, EMBASE and the Cochrane central register of controlled trials were searched up to June 2016 by two independent investigators. Studies were considered eligible if they recruited adult MI patients and reported hazard ratio (HR) for all-cause mortality comparing those who received blood transfusion with those who did not receive blood transfusion. We abstracted and calculated pooled HRs using a random-effects model. Results: From 4277 unique reports, we identified 17 studies including 260811 patients with 11 studies examining short-term (in hospital/30-day) all-cause mortality and 9 studies examining long-term (more than 30 days) all-cause mortality. Meta-analysis demonstrated that patients treated with blood transfusion had increased short-term all-cause mortality (HR, 2.39, 95% CI 1.81 to 3.15) compared with those without blood transfusion treatment. Similar findings were observed by subgroup analyses. We also find significant association between blood transfusion and long-term all-cause mortality (HR 1.90, 95% CI 1.40 to 2.58) for MI patients. Conclusions: In patients with MI, blood transfusion treatment is associated with patient short-term and long-term all-cause mortality. However, further large-scale prospective studies are needed to establish its validity of this association.
Restrictive versus liberal blood transfusion in patients with coronary artery disease: a meta-analysis
Current Medical Research and Opinion. 2017;:1-17.
OBJECTIVES To compare clinical outcomes between restrictive versus liberal blood transfusion strategies in patients with coronary artery disease (CAD). RESEARCH DESIGN AND METHODS A literature search from January 1966 to May 2016 was performed in Pubmed, EMBASE and Cochrane Library to find trials evaluating a restrictive hemoglobin transfusion trigger of ≤8 g/dL, compared with a more liberal trigger. Two study authors independently extracted data from the trials. Primary outcome was mortality and secondary outcome was subsequent myocardial infarction. Relative risk (RR) with their 95% confidence intervals (CIs) was assessed. RESULTS Six trials involving 133,058 participants were included in this study. Pooled results revealed no difference in mortality was found between the liberal transfusion and restrictive transfusion (RR = 1.17, 95% CI = 0.91-1.52, P = 0.22). Subgroup analysis revealed that restrictive transfusion strategy was associated with a higher risk of in-hospital mortality (RR = 1.38, 95% CI = 1.15-1.67, P < 0.001) and 30-day mortality (RR = 1.21, 95% CI = 1.01-1.45, P = 0.03), compared with the liberal strategy. No significant difference was found between the liberal transfusion strategy and restrictive transfusion strategy in risk for subsequent myocardial infarction (RR = 1.09, 95% CI = 0.57-2.06, P = 0.80). LIMITATIONS Limitations include (1) limited number of trials, especially those evaluating myocardial infarction, (2) observed heterogeneity, (3) confounding by indication and other inherent bias may exist. CONCLUSION The findings suggest that restrictive blood transfusion was associated with higher in-hospital and 30-day mortality than liberal blood transfusion in CAD patients. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by RCTs.
Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis
OBJECTIVE To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery. DESIGN Systematic review and meta-analysis. DATA SOURCES Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible. TRIAL SELECTION Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease. DATA EXTRACTION AND SYNTHESIS Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios. MAIN OUTCOME MEASURES 30 day mortality, and cardiovascular events. RESULTS 41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I(2)=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I(2)=0%). CONCLUSIONS The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease. REGISTRATION PROSPERO CRD42014014251.Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.