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Original Investigation | Less Is More

Association of Blood Transfusion With Increased Mortality in Myocardial Infarction:  A Meta-analysis and Diversity-Adjusted Study Sequential Analysis

Saurav Chatterjee, MD; Jørn Wetterslev, MD, PhD; Abhishek Sharma, MD; Edgar Lichstein, MD; Debabrata Mukherjee, MD, MS
JAMA Intern Med. 2013;173(2):132-139. doi:10.1001/2013.jamainternmed.1001.
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Background  The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists.

Methods  A systematic search of studies published between January 1, 1966, and March 31, 2012, was conducted using MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. English-language studies comparing blood transfusion with no blood transfusion or a liberal vs restricted blood transfusion strategy were identified. Two study authors independently reviewed 729 originally identified titles and abstracts and selected 10 for analysis. Study title, follow-up period, blood transfusion strategy, and mortality outcomes were extracted manually from all selected studies, and the quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology checklist.

Results  Studies of blood transfusion strategy in anemia associated with myocardial infarction were abstracted, as well as all-cause mortality rates at the longest available follow-up periods for the individual studies. Pooled effect estimates were calculated with random-effects models. Analyses of blood transfusion in myocardial infarction revealed increased all-cause mortality associated with a strategy of blood transfusion vs no blood transfusion during myocardial infarction (18.2% vs 10.2%) (risk ratio, 2.91; 95% CI, 2.46-3.44; P < .001), with a weighted absolute risk increase of 12% and a number needed to harm of 8 (95% CI, 6-17). Multivariate meta-regression revealed that blood transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P = .03).

Conclusions  Blood transfusion or a liberal blood transfusion strategy compared with no blood transfusion or a restricted blood transfusion strategy is associated with higher all-cause mortality rates. A practice of routine or liberal blood transfusion in myocardial infarction should not be encouraged but requires investigation in a large trial with low risk for bias.

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Figure 1. Search strategy according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) checklist.40 CABG indicates coronary artery bypass graft.

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Figure 2. Risk for all-cause mortality with liberal blood transfusion. M-H indicates Mantel-Haenszel. Diamond indicates the overall summary estimate for the analysis (width of the diamond represents the 95% CI); boxes, the weight of individual studies in the pooled analysis; whiskers, the 95% CIs: when they are to the left of the midline, representing a risk ratio of 1, it means that the risks of dying favor (ie, are less with) tranfusion; when they are to the right of the midline, representing a risk ratio of 1, it means that the risks of dying favor (ie, are less with) the comparator arm; if the lines touch the midline, representing a risk ratio of 1, it means that the risks of dying are comparable for transfusion and the comparators.

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Figure 3. Trim-and-fill adjustment for assessment of publication bias. RD indicates risk difference.

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Figure 4. Study sequential analysis of observational studies on all-cause mortality with a 20% relative risk increase (RRI), number needed to harm of 50, control event proportion of 10%, α = .05, β = .10, diversity (D2) of 97%, and required information size of 320 310. The analysis uses a random-effects model with a type I error risk of 5% and a power of 90%. The blue line is the cumulative z score from the cumulative random-effects meta-analyses, and each black box indicates the addition of data from a new study; the red lines are the study sequential monitoring boundaries calculated according to the O’Brien-Fleming α-spending function and stopping rule. The red vertical line indicates the diversity-adjusted information size of 320 310 patients based on an a priori 20% RRI corresponding to a number needed to harm of 50. There seems to be evidence for a 20% RRI even when the cumulative meta-analysis is adjusted for sparse data and multiple testing on accumulated data, disregarding possible bias.

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Figure 5. Risk for myocardial infarction with liberal blood transfusion (Tx). M-H indicates Mantel-Haenszel. Diamond indicates the overall summary estimate for the analysis (width of the diamond represents the 95% CI); boxes, the weight of individual studies in the pooled analysis; whiskers, the 95% CIs: when they are to the left of the midline, representing a risk ratio of 1, it means that the risks of myocardial infarction (ie, are less with) liberal Tx/Tx; when they are to the right of the midline, representing a risk ratio of 1, it means that the risks of dying favor (ie, are less with) the comparator arm; if the lines touch the midline, representing a risk ratio of 1, it means that the risks of a myocardial infarction are comparable for the 2 arms.

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