Anaemia in heart failure patients: the prevalence of haematinic deficiencies and the role of ACE inhibitors and aspirin doses as risk factors

Keywords: Anemia, Angiotensin-Converting Enzyme Inhibitors, Aspirin, Drug-Related Side Effects and Adverse Reactions, Heart Failure, Risk Assessment, Multivariate Analysis, Clinical Audit, Australia


Background: Patients with heart failure often have comorbidities that alter the progression of heart failure and impact on prognosis. One such comorbidity is anaemia, and clinicians have started to appreciate the full gravity of its impact on heart failure patients. Yet, the extent of the problem is not fully understood, particularly the role of heart failure therapy itself as a risk factor for developing anaemia.

Objective: This study aimed to investigate the prevalence of anaemia in a cohort of heart failure patients. The impact of using different ACEIs and different doses of aspirin was also explored, together with the prevalence of haematinic deficiencies.

Methods: Medication lists and pathology results were examined to establish the prevalence of ACEIs use, and the use of aspirin at its most common doses of 100mg and 150mg, together with haematinic deficiencies. Multinomial logistic regression and the Student’s t-test were utilised for the analysis of data. Statistical significance was pre-set at p<0.05.

Results: Ninety-six patients were eligible for analysis, with 26% having anaemia. The use of ACEIs had a RR of 17.4 for the presence of anaemia. Perindopril was associated with a RR of 20.8, while the use of ramipril was not significantly associated with such a high RR. Haematinic anaemia occurred only at a rate of 3.3%, but borderline deficiencies were found in more than a third of all patients. An aspirin dose of 150mg was associated with a higher risk for anaemia, compared to a dose of 100mg.

Conclusions: ACEIs are associated with the presence of anaemia, with perindopril posing more risk than ramipril when used in heart failure patients. The dose of aspirin may also be a factor in the development of anaemia, with lower doses being safer. Despite the lack of high prevalence of haematinic anaemia among this cohort of patients, borderline haematinic deficiencies were common.


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Ishani A, Weinhandl E, Zhao Z, Gilbertson DT, Collins AJ, Yusuf S, Herzog CA. Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2005; 45(3):391-399.

Silverberg DS, Wexler D, Iaina A, Steinbruch S, Wollman Y, Schwartz D. Anemia, chronic renal disease and congestive heart failure-the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists. Int Urol Nephrol. 2006; 38(2):295-310.

Witte KKA, Desilva R, Chattopadhyay S, Ghosh J, Cleland JGF, Clark AL. Are hematinic deficiencies the cause of anemia in chronic heart failure? Am Heart J. 2004;147(5):924-930.

Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation. 2003;107(2):223-225.

Hitt E. Anaemia correction improves cardiac and renal function in patients with congestive heart failure. (accessed Jan 10, 2019).

Mancini DM, Katz SD, Lang CC, La Manca J, Hudaihed A, Androne AS. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003;107(2):294-299.

Silverberg DS, Wexler D, Sheps D, Blum M, Keren G, Baruch R, Schwartz D, Yachnin T, Steinbruch S, Shapira I, Laniado S, Iaina A. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol. 2001;37(7):1775-1780.

Ponikowski P, Anker SD, Szachniewicz J, Okonko D, Ledwidge M, Zymlinski R, Ryan E, Wasserman SM, Baker N, Rosser D, Rosen SD, Poole-Wilson PA, Banasiak W, Coats AJ, McDonald K. Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2007;49(7):753-762.

Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet. 2007;369(9559):381-388.

Silverberg DS, Wexler D, Blum M, Iaina A. The cardio renal anemia syndrome: correcting anemia in patients with resistant congestive heart failure can improve both cardiac and renal function and reduce hospitalizations. Clin Nephrol. 2003;60(Suppl 1):S93-S102.

Austin PC, Steyerbergd EW. The number of subjects per variable required in linear regression analyses. J Clin Epidemiol. 2015;68(6):627-636.

Marathias KP, Agroyannis B, Mavromoustakos T, Matsoukas J, Vlahakos DV. Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Curr Top Med Chem. 2004;4(4):483-486.

Wang AY, Yu AW, Lam CW, Yu LM, Li PK, Goh J, Lui SF. Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis. Am J Kidney Dis. 2002 Mar;39(3):600-8.

Mohanram A, Zhang Z, Shahinfar S, Lyle PA, Toto RD. The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes. Kidney Int. 2008;73(5):630-636.

Plata R, Cornejo A, Arratia C, Anabaya A, Perna A, Dimitrov BD, Remuzzi G, Ruggenenti P; Commission on Global Advancement of Nephrology (COMGAN), Research Subcommittee of the International Society of Nephrology. Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: a prospective randomised trial. Lancet. 2002;359(9307):663-666.

Glicklich D, Kapoian T, Mian H, Gilman J, Tellis V, Croizat H. Effects of erthropoietin, angiotensin II, and angiotensin-converting enzyme inhibitor on erythroid precursors in patients with posttransplantation erythrocytosis. Transplantation. 1999;68(1):62-66.

Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE. Enalapril-associated anaemia in renal transplant recipients treated for hypertension. Am J Kidney Dis. 1991;17(2):199-205.

Macdougall IC. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin. Nephrol Dial Transplant. 1999;14(8):1836-1841.

Azizi M, Rousseau A, Ezan E, Guyene TT, Michelet S, Grognet JM, Lenfant M, Corvol P, Ménard J. Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J Clin Invest. 1996;97(3):839-44.

Chisi JE, Wdzieczak-Bakala J, Thierry J, Briscoe CV, Riches AC. Captopril inhibits the proliferation of hematopoietic stem and progenitor cells in murine long-term bone marrow cultures. Stem Cells. 1999;17(6):339-344.

Padilla, O. Normal laboratory values. Merck Manuals; (accessed Jan 11, 2019).

How to Cite
Guirguis K. Anaemia in heart failure patients: the prevalence of haematinic deficiencies and the role of ACE inhibitors and aspirin doses as risk factors. Pharm Pract (Granada) [Internet]. 2019Mar.13 [cited 2021Sep.22];17(1):1406. Available from:
Original Research