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

Abstract

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 Authors were contacted for data whenever possible.Trial selection Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.Data extraction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 (I2=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, I2=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.

Anemia and Blood Transfusion in the Critically Ill Patient with Cardiovascular Disease

“…Two recent systematic reviews in cardiac surgery [19] and in perioperative transfusion practice (including cardiac surgery) [20] reported higher mortality with a restrictive transfusion threshold. Our systematic review [21] found only 11 blood transfusion threshold randomized controlled trials (RCTs) that included patients with co-existing CVD, either as the whole population [10,[22][23][24], as a pre-defined subgroup [9,11,25] or as a high proportion of patients [14,[26][27][28]. We found no evidence of a difference in 30-day mortality between restrictive and liberal transfusion thresholds.…”

“…*Additional risk of bias assessed as to completeness of patients recruited into clusters (this was graded as low risk). Modified from [21] with permission more manageable. If no difference is found, then we could say with confidence that patients with CVD do not benefit from higher transfusion thresholds.…”

“…In a population in which patients are not sedated and ventilated, an alternative could be to transfuse based on symptomatology, or potentially anaerobic threshold, but this is unlikely to be feasible in the ICU. Thresholds have varied between trials (restrictive 7.0-9.7 g/dl, liberal 9.0-11.3 g/dl [21]), with overlap between restrictive thresholds in some trials and liberal in others. The larger the difference in thresholds, the more likely a difference will be shown, and a trial of 7 g/dl (current practice excepting ACS) vs 90 g/l would need fewer patients than 7.5-8.0 g/dl vs 9.0 g/dl.…”

Context-dependent risks and benefits of transfusion in the critically ill

“…In a meta-analysis of nine RCTs enrolling patients with cardiovascular diseases (N=2,609) who underwent major noncardiac surgery, the risk of acute coronary syndrome in patients managed with restricted transfusion target (<8 g/dL) was significantly higher than those managed with a liberal transfusion target (>8 g/dL) (relative risk 1.8, 95% CI: 1.3-2.7, p=0.01, I 2 =0%). 33 In another meta-analysis including 31 RCTs on adult surgical and critically ill patients, the benefits of allogeneic RBC transfusions were shown to be context-dependent, with a reduced risk of mortality and composite morbidity after using liberal transfusion only in higher risk patients including those who underwent cardiac/vascular procedures and elderly orthopedic patients. 34 Under normal circumstances, myocardial oxygen extraction is at its maximal capacity and any reductions in oxygen carrying capacity caused by anemia are compensated by an increase in coronary blood flow.…”

“…[32][33][34] A Brazilian single-center RCT (N=198) reported that using a liberal transfusion target (9 g/dL) for surgical oncology patients was associated with a lower risk of mortality and postoperative complications than a more restricted transfusion target (7 g/dL) (absolute risk reduction in the composite end point of all adverse outcomes 16%, 95% confidence interval [CI]: 3.8-28.2). 32 Why moderate anemia with a restricted transfusion target is not well tolerated for some surgical oncology patients is unclear, but it is possible that the physiological reserve of these cancer patients is already substantially compromised by the underlying cancers and/ or the associated chemo-or radiotherapy.…”