IntroductionThe 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). MethodsWe used AMSTAR2 to assess the methodological quality of systematic reviews and grade the available research. The primary endpoint was all-cause mortality. ResultsUsing 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. ConclusionPatients 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.