Anemia and mortality in acute coronary syndromes: A systematic review and meta-analysis

doi:10.1016/j.ahj.2012.10.024

American Heart Journal

Volume 165, Issue 2, February 2013, Pages 143-153.e5

https://doi.org/10.1016/j.ahj.2012.10.024 Get rights and content

Background

Anemia is a common comorbidity among patients with acute coronary syndromes (ACS) and may adversely affect cardiovascular outcomes in these patients. We conducted a systematic review and meta-analysis to examine the association between anemia and mortality among patients with ACS.

Methods

We systematically searched MEDLINE to identify cohort studies and secondary analyses of randomized controlled trials examining the association between anemia and all-cause mortality among patients with ACS. Data were aggregated at 4 follow-up times (inhospital, 30 days, 1 year, and maximal available follow-up) using random-effects meta-analysis models.

Results

Twenty-seven studies met the inclusion criteria, involving 233,144 patients. Anemia was present in 44,519 (19.1%) of these patients. Anemic patients were generally older and had a higher prevalence of comorbidities including diabetes mellitus, congestive heart failure, cerebrovascular disease, and history of major bleeding. Anemia was associated with an increased risk of crude all-cause mortality (relative risk 2.08, 95% CI 1.70-2.55) and reinfarction (relative risk 1.25, 95% CI 1.02-1.53) at maximal available follow-up. When adjusted risk ratios from individual studies' multivariable regression analyses were pooled, the magnitude of the associated mortality risk was attenuated but remained significant at maximal follow-up (hazard ratio 1.49, 95% CI 1.23-1.81). Clinically and statistically significant increases in mortality were observed as early as at 30 days post-ACS and persisted at 1 year.

Conclusions

Anemia in patients with ACS is independently associated with a significantly increased risk of early and late mortality.

Section snippets

Methods

We conducted this systematic review and meta-analysis following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group guidelines.⁵

Search results

Our search strategy identified 693 potentially relevant articles, of which 74 were reviewed as full articles (Figure 1). Twenty-seven studies that met our inclusion criteria were included in our systematic review and meta-analysis.7, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35

Study and patient characteristics

The characteristics of the 27 identified studies are shown in Table I, including study design, population, definition of anemia, type of ACS, exclusions, and

Discussion

Our study was designed to examine the association between anemia and cardiovascular outcomes in patients presenting with ACS. Anemia was a common clinical finding in these studies and prevalent in almost 20% of patients with ACS. Our results show that anemia is associated with a clinically and statistically significant increase in adjusted risk of mortality after ACS, which, to some extent, may be driven by an increased risk of reinfarction. Anemia was clearly observed more often in patients

Conclusion

Anemia is independently associated with a substantially increased risk of mortality among patients with ACS. Further studies are warranted to examine if correcting anemia in these patients averts this risk and improves survival in this patient population.

Disclosures

Dr Filion is a Canadian Institutes of Health Research New Investigator. Dr Eisenberg is a Chercheur-National of the Fonds de la Recherche du Québec-Santé.

Acknowledgements

We would like to thank Sami and Dr Jack Lawler for their editorial assistance.

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The individual studies vary in their reported endpoints. For example, the meta-analysis by Lawler et al. contains data about the in-hospital, 30-day- and one year mortality [33]. Furthermore, they collected data about the outcome at the maximum available follow up.
The role of erythrocytes in the acute coronary syndrome (ACS) is complex. The aim of this review in terms of PICO (P: patients; I: intervention; C: comparison; O: outcome) was to summarize systematic reviews in patients (P) with acute coronary syndrome, evaluating the effects of (I) 1) iron deficiency, 2) administration of an erythropoiesis-stimulating agent (ESA), 3) anemia on admission, 4) red blood cell transfusion, 5) a restrictive transfusion strategy in comparison (C) to 1) no iron deficiency, 2) no ESA 3) no anemia on admission, 4) no red blood cell transfusion, 5) a liberal transfusion strategy on mortality (O).
We used AMSTAR2 to assess the methodological quality of systematic reviews and grade the available research. The primary endpoint was all-cause mortality.
Using the data from 2,787,005 patients, the following conditions were associated with worse outcome in patients with ACS: anemia on admission (RR 2.08 95%CI 1.70–2.55) and transfusion (1.93 95%CI 1.12–3.34) of red blood cells. A liberal transfusion (RR 0.86 95%CI 0.70–1-05), administration of ESA (RR 0.55 95%CI 0.22–1.33) and iron deficiency (OR 1.24 95%CI 0.12–13.13) were not associated with altered all-cause mortality.
Patients suffering from ACS and anemia on admission are at particular risk for adverse outcome. There is evidence of associations between adverse outcomes and receiving red blood cell transfusions.
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The lower the baseline Hb level is in patients with ACS, treated with an invasive approach, the higher the risk for subsequent adverse events, especially major bleeding and mortality. In a metanalysis10 involving 233 114 patients with ACS, anaemia was associated with an increased risk of crude all-cause mortality (relative risk 2.08, 95% CI 1.70–2.55) and reinfarction (relative risk 1.25, 95% CI 1.02–1.53) at maximal available follow-up. A common feature observed in all these studies is that anaemia is strongly associated with elderly, frailty and comorbidities.8
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Transfusion in Older Anemic Patients: Should the Troponin Value Be Taken into Account?
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Anemia is common in older individuals, but it is not known whether the prognostic impact of transfusion differs according to cardiac troponin concentration.
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Of the 514 anemic patients included (median age 88 years), 157 (31%) had elevated troponin concentrations. These patients were more likely to die at 30 days (49% vs 27%, P < .001) and 1 year (65% vs 51%, P = .004) than patients with normal values. Among patients with elevated troponin concentrations, 30-day mortality tended to be lower in transfused than in not-transfused patients (hazard ratio 0.48; 95% confidence interval, 0.21-1.08; P = .07). This association was not found in patients without troponin elevation (hazard ratio 1.09; 95% CI, 0.61-1.93; P = .8). Transfusion was associated with 30-day survival in patients with hemoglobin ≤8 g/dL. It was also associated with excess 1-year mortality in patients with hemoglobin >8 g/dL.
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Curriculum in CardiologyAnemia and mortality in acute coronary syndromes: A systematic review and meta-analysis

Background

Methods

Results

Conclusions

Section snippets

Methods

Search results

Study and patient characteristics

Discussion

Conclusion

Disclosures

Acknowledgements

Am J Cardiol

Am Heart J

Am Heart J

Am Heart J

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am Heart J

Rev Esp Cardiol

Am J Cardiol

Am J Cardiol

Am J Kidney Dis

Am J Cardiol

Kidney Int

Int J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Curriculum in Cardiology
Anemia and mortality in acute coronary syndromes: A systematic review and meta-analysis