Hemoglobin and Change in Hemoglobin Status Predict Mortality, Cardiovascular Events, and Bleeding in Stable Coronary Artery Disease

Paul R. Kalra, Nicola Greenlaw, Roberto Ferrari, Ian Ford, Jean-Claude Tardif, Michal Tendera, Christopher M. Reid, Nicolas Danchin, Janina Stepinska, Ph. Gabriel Steg, Kim M. Fox, ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) Investigators

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Background Anemia is a predictor of adverse outcomes in acute myocardial infarction. We studied the relationship of hemoglobin, or its change over time, and outcomes in patients with stable coronary artery disease. Methods The ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease is a prospective, cohort study of outpatients with stable coronary artery disease (32,901 in 45 countries 2009-2010): 21,829 with baseline hemoglobin levels. They were divided into hemoglobin quintiles and anemia status (anemic or normal at baseline/follow-up: normal/normal; anemic/normal; normal/anemic; anemic/anemic. All-cause mortality, cardiovascular events, and major bleeding at 4-year follow-up were assessed. Results Low baseline hemoglobin was an independent predictor of all-cause, cardiovascular, and noncardiovascular mortality, the composite of cardiovascular death/myocardial infarction or stroke and major bleeds (all P <.001; unadjusted models). Anemia at follow-up was independently associated with all-cause mortality (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.55-2.33 for anemic/anemic; 1.87; 1.54-2.28 for normal/anemic; both P <.001), noncardiovascular mortality (P <.001), and cardiovascular mortality (P =.001). Patients whose baseline anemia normalized (anemic/normal) were not at increased risk of death (HR, 1.02; 95% CI, 0.77-1.35), although the risk of major bleeding was greater (HR, 2.06; 95% CI, 1.23-3.44; P =.013) than in those with normal hemoglobin throughout. Sensitivity analyses excluding patients with heart failure and chronic kidney disease at baseline yielded qualitatively similar results. Conclusions In this large population with stable coronary artery disease, low hemoglobin was an independent predictor of mortality, cardiovascular events, and major bleeds. Persisting or new-onset anemia is a powerful predictor of cardiovascular and noncardiovascular mortality.

Original languageEnglish
Pages (from-to)720-730
Number of pages11
JournalThe American Journal of Medicine
Issue number6
Publication statusPublished - Jun 2017


  • Anemia
  • Coronary artery disease
  • Hemoglobin

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