• Ghada Muthana Ahmed Nineveh health directorate, Mosul, Nineveh province-Iraq
  • Fawaz Abdulghani Alassaf Department of Pharmacology and Toxicology, University of Mosul, College of Pharmacy, Mosul, Nineveh province-Iraq. College of Medicine, University of Warith Al-Anbiyaa, Karbala-Iraq
  • Mohammed Najim Abed Department of Pharmaceutical Chemistry, University of Mosul, College of Pharmacy, Mosul, Nineveh province-Iraq



Angiotensin receptor blockers, Hematological abnormalities, Anemia


Antihypertensive medications known as angiotensin receptor blockers (ARBs) have become increasingly popular for treating conditions beyond hypertension. The reason for this widespread use is mainly due to its reno-protective and cardioprotective properties in patients with congestive heart failure and diabetes mellitus. There have been conflicting studies on the relationship between ARBs and haematological abnormalities. Using the supplied search terms, we carried out a thorough search for relevant papers written in English and published before January 2024. All of the studies that met the selection criteria were searched for on PubMed, Cochrane Library, and Google Scholar. Based on the examined data from the searched literature, it has been demonstrated that angiotensin II is essential for the stimulation of erythropoiesis and inhibition of it by drugs such as ARBs can lower haematocrit levels, leading to anaemia. Accordingly, dose reduction or stopping the administration of ARBs could be a choice for the correction of anaemia. However, such a decision is based on the clinical situation and the requirements for other management options.

Author Biographies

Ghada Muthana Ahmed, Nineveh health directorate, Mosul, Nineveh province-Iraq


Fawaz Abdulghani Alassaf, Department of Pharmacology and Toxicology, University of Mosul, College of Pharmacy, Mosul, Nineveh province-Iraq. College of Medicine, University of Warith Al-Anbiyaa, Karbala-Iraq


Mohammed Najim Abed, Department of Pharmaceutical Chemistry, University of Mosul, College of Pharmacy, Mosul, Nineveh province-Iraq



Brugts JJ, Boersma E, Chonchol M, Deckers JW, Bertrand M, Remme WJ, et al. The cardioprotective effects of the angiotensin-converting enzyme inhibitor perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency: insights from the EUROPA trial. J Am Coll Cardiol 2007;50(22):2148–55.

Mahmood IH, Abed MN, Merkhan MM. Effects of blocking of angiotensin system on the prevalence of metabolic syndrome in type 2 diabetic patients. Pak J Med Sci 2012;29(1):140–3.

Marusic-Vrsalovic M, Dominis M, Jaksic B, Kusec R. Angiotensin I-converting enzyme is expressed by erythropoietic cells of normal and myeloproliferative bone marrow. Br J Haematol 2003;123(3):539–41.

Marathias K, Agroyannis B, Mavromoustakos T, Matsoukas J, Vlahakos D. 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):483–6.

Cheungpasitporn W, Thongprayoon C, Chiasakul T, Korpaisarn S, Erickson SB. Renin-angiotensin system inhibitors linked to anemia: a systematic review and meta-analysis. QJM 2015;108(11):879–84.

Plata R, Cornejo A, Arratia C, Anabaya A, Perna A, Dimitrov BD, et al. Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: A prospective randomised trial. Lancet 2002;359(9307):663–6.

Winkelmayer WC, Kewalramani R, Rutstein M, Gabardi S, Vonvisger T, Chandraker A. Pharmacoepidemiology of anemia in kidney transplant recipients. J Am Soc Nephrol 2004;15(5):1347–52.

Inoue A, Babazono T, Iwamoto Y. Effects of the Renin-Angiotensin system blockade on hemoglobin levels in type 2 diabetic patients with chronic kidney disease. Am J Hypertens 2008;21(3):317–22.

Fountain JH, Kaur J, Lappin SL. Physiology, Renin Angiotensin System. 2023 Mar 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.

Tetzner A, Gebolys K, Meinert C, Klein S, Uhlich A, Trebicka J, et al. G-Protein-Coupled Receptor MrgD Is a Receptor for Angiotensin-(1-7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A. Hypertension 2016;68(1):185–94.

Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/angiotensin 1-7 axis of the renin-angiotensin system in heart failure. Circ Res 2016;118(8):1313–26.

Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. UltraRapid Communication A Novel Angiotensin-Converting Enzyme – Related to Angiotensin 1-9. Circ Res 2000;87:1–9.

Zhuo JL, Li XC. New insights and perspectives on intrarenal renin-angiotensin system: Focus on intracrine/intracellular angiotensin II. Peptides 2011;32(7):1551–65.

Villapol S, Saavedra JM. Neuroprotective Effects of Angiotensin Receptor Blockers. Am J Hypertens 2015;28(3):289–99.

Alnori H, Alassaf FA, Alfahad M, Qazzaz ME, Jasim M, Abed MN. Vitamin D and Immunoglobulin E Status in Allergic Rhinitis Patients Compared to Healthy People. J Med Life 2020;13(4):463–8.

Yosypiv IV. Renin-angiotensin system in mammalian kidney development. Pediatr Nephrol 2021;36(3):479–89.

Bagby SP, Lebard LS, Luo Z, Ogden BE, Corless C, Mcpherson ED, et al. ANG II AT 1 and AT 2 receptors in developing kidney of normal microswine. Am J Physiol Renal Physiol 2002;283(4):755–64.

Norwood VF, Craig MR, Harris JM, Gomez RA. Differential expression of angiotensin II receptors during early renal morphogenesis. Am J Physiol 1997;272(2 Pt 2):R662–8.

Schrankl J, Fuchs M, Broeker K, Daniel C, Kurtz A, Wagner C. Localization of angiotensin II type 1 receptor gene expression in rodent and human kidneys. Am J Physiol Renal Physiol 2021;320(4):F644–53.

Li XC, Zhuo JL. Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension. Curr Hypertens Rep 2016;18(8):63.

Pei N, Mao Y, Wan P, Chen X, Li A, Chen H, et al. Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer. J Exp Clin Cancer Res 2017;36(1):77.

La Sierra A. Angiotensin receptor blockers in hypertension and cardiovascular diseases. Cardiovasc Hematol Agents Med Chem 2006;4(1):67–73.

Steckelings UM, Artuc M, Wollschläger T, Wiehstutz S, Henz BM. Angiotensin-converting enzyme inhibitors as inducers of adverse cutaneous reactions. Acta Derm Venereol 2001;81(5):321–5.

Raimondo DDi, Tuttolomondo A, Buttà C, Miceli S, Licata G, Pinto A. Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation. Curr Pharm Des 2012;18(28):4385–413.

Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARγ–modulating activity. Hypertension 2004;43(5):993–1002.

Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA 2008;300(8):924–32.

Silveira KD, Coelho FM, Vieira AT, Barroso LC, Queiroz CM, Costa VV, et al. Mechanisms of the anti-inflammatory actions of the angiotensin type1 receptor antagonist losartan in experimental models of arthritis. Peptides 2013;46:53–63.

Mrug M, Stopka T, Julian BA, Prchal JF, Prchal JT. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 1997;100(9):2310.

Kato H, Ishida J, Imagawa S, Saito T, Suzuki N, Matsuoka T, et al. Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor. FASEB J 2005;19(14):2023–5.

Doan TN, Gletsu N, Cole J, Bernstein KE. Genetic manipulation of the renin-angiotensin system. Curr Opin Nephrol Hypertens 2001;10(4):483–91.

Naito M, Kawashima A, Akiba T, Takanashi M, Nihei H. Effects of an angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitors on burst forming units-erythroid in chronic hemodialysis patients. Am J Nephrol 2003;23(5):287–93.

Jelkmann W. Regulation of erythropoietin production. J Physiol 2011;589(Pt 6):1251.

Nakamoto H, Kanno Y, Okada H, Suzuki H. Erythropoietin resistance in patients on continuous ambulatory peritoneal dialysis. Adv Perit Dial 2004;20:111–6.

Hu X, li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther 2021;6(1):1–33.

Yasuoka Y, Izumi Y, Fukuyama T, Inoue H, Oshima T, Yamazaki T, et al. Effects of Angiotensin II on Erythropoietin Production in the Kidney and Liver. Molecules 2021;26(17):5399.

Ahmed GM, Abed MN, Alassaf FA. Impact of calcium channel blockers and angiotensin receptor blockers on hematological parameters in type 2 diabetic patients. Naunyn Schmiedebergs Arch Pharmacol. 2023. doi: 10.1007/s00210-023-02731-y.

An JN, Hwang JH, Lee JP, Chin HJ, Kim S, Kim DK, et al. The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial. PLoS One 2015;10(6):e0128632.

Singer CE, Vasile CM, Popescu M, Popescu AIS, Marginean IC, Iacob GA, et al. Role of Iron Deficiency in Heart Failure-Clinical and Treatment Approach: An Overview. Diagnostics (Basel) 2023;13(2):304.

Westenbrink BD, Visser FW, Voors AA, Smilde TDJ, Lipsic E, Navis G, et al. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J 2007;28(2):166–71.

Jensen JD, Eiskjær H, Bagger JP, Pedersen EB. Elevated level of erythropoietin in congestive heart failure relationship to renal perfusion and plasma renin. J Intern Med 1993;233(2):125–30.

Kato H, Ishida J, Matsusaka T, Ishimaru T, Tanimoto K, Sugiyama F, et al. Erythropoiesis and Blood Pressure Are Regulated via AT1 Receptor by Distinctive Pathways. PLoS One 2015;10(6):e0129484.

Gossmann J, Burkhardt R, Harder S, Lenz T, Sedlmeyer A, Klinkhardt U, et al. Angiotensin II infusion increases plasma erythropoietin levels via an angiotensin II type 1 receptor-dependent pathway. Kidney Int 2001;60(1):83–6.

Ishizaka N, Saito K, Noiri E, Sata M, Ikeda H, Ohno A, et al. Administration of ANG II induces iron deposition and upregulation of TGF-beta1 mRNA in the rat liver. Am J Physiol Regul Integr Comp Physiol 2005;288(4):R1063–70.

Tajima S, Tsuchiya K, Horinouchi Y, Ishizawa K, Ikeda Y, Kihira Y, et al. Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells. Hypertens Res 2010;33(7):713–21.

Tajima S, Ikeda Y, Enomoto H, Imao M, Horinouchi Y, Izawa-Ishizawa Y, et al. Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice. Eur J Nutr 2015;54(5):709–19.

Rodgers KE, Xiong S, Steer R, diZerega GS. Effect of angiotensin II on hematopoietic progenitor cell proliferation. Stem Cells 2000;18(4):287–94.

Shen XZ, Bernstein KE. The peptide network regulated by angiotensin converting enzyme (ACE) in hematopoiesis. Cell Cycle 2011;10(9):1363.

Cao DY, Saito S, Veiras LC, Okwan-Duodu D, Bernstein EA, Giani JF, et al. Role of angiotensin-converting enzyme in myeloid cell immune responses. Cell Mol Biol Lett 2020;25(1):1–12.

Kim S, Zingler M, Harrison JK, Scott EW, Cogle CR, Luo D, et al. Angiotensin II Regulation of Proliferation, Differentiation and Engraftment of Hematopoietic Stem Cells. Hypertension 2016;67(3):574.

Lo  Pez-Farre A, Sa  Nchez De Miguel L, Ân MM, Jime Ânez A, Lopez-Bloya A, Go  Mez J, et al. Angiotensin II AT1 receptor antagonists and platelet activation. Nephrol Dial Transplant 2001;16:45–9.

Montezano AC, Nguyen Dinh Cat A, Rios FJ, Touyz RM. Angiotensin II and vascular injury. Curr Hypertens Rep 2014;16(6):431.

Ahmed GM, Abed MN, Alassaf FA. An overview of the effects of sodium-glucose co-transporter-2 inhibitors on hematological parameters in diabetic patients. Iraqi J Pharm 2023;20(1):65–71.

Alicic RZ, Neumiller JJ, Johnson EJ, Dieter B, Tuttle KR. Sodium–Glucose Cotransporter 2 Inhibition and Diabetic Kidney Disease. Diabetes 2019;68(2):248–57.

Shinozaki K, Ayajiki K, Nishio Y, Sugaya T, Kashiwagi A, Okamura T. Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance. Hypertens 2004;43(2):255–62.

Underwood PC, Adler GK. The Renin Angiotensin Aldosterone System and Insulin Resistance in Humans. Curr Hypertens Rep 2013;15(1):59.

Peti-Peterdi J, Kang JJ, Toma I. Activation of the renal renin–angiotensin system in diabetes—new concepts. Nephrol Dial Transplant 2008;23(10):3047.

Vlahakos DV, Marathias KP, Madias NE. The role of the renin-angiotensin system in the regulation of erythropoiesis. Am J Kidney Dis 2010;56(3):558–65.

Ahmed GM, Abed MN, Alassaf FA. The Diabetic-Anemia Nexus: Implications for Clinical Practice. Mil Med Sci Lett. 2023;92:1–11.

Cole J, Ertoy D, Lin H, Sutliff RL, Ezan E, Guyene TT, et al. Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient mice. J Clin Invest 2000;106(11):1391–8.

Raptis AE, Bacharaki D, Mazioti M, Marathias KP, Markakis KP, Raptis SA, et al. Anemia due to coadministration of renin-angiotensin-system inhibitors and PPARγ agonists in uncomplicated diabetic patients. Exp Clin Endocrinol Diabetes 2012;120(7):416–9.

Alzoubi B, Kharel A, Machhi R, Aziz F, Swanson KJ, Parajuli S. Post-transplant erythrocytosis after kidney transplantation: A review. World J Transplant 2021;11(6):220.

Vlahakos DV, Marathias KP, Kosmas EN. Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis. Ann Intern Med 2001;134(5):426–7.

Dunlay SM, Weston SA, Redfield MM, Killian JM, Roger VL. Anemia and heart failure: a community study. Am J Med 2008;121(8):726–32.

Kamper AL, Nielsen OJ. Effect of enalapril on haemoglobin and serum erythropoietin in patients with chronic nephropathy. Scand J Clin Lab Invest 1990;50(6):611–8.

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):924–30.

Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG, et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 2006;48(12):2485–9.

Macdougall IC, Cooper AC. Hyporesponsiveness to erythropoietic therapy due to chronic inflammation. Eur J Clin Invest 2005;35(Suppl 3)(3):32–5.

Iversen PO, Woldbaek PR, Tønnessen T, Christensen G. Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J Physiol Regul Integr Comp Physiol 2002;282(1):R166–72.

Jankowska EA, Malyszko J, Ardehali H, Koc-Zorawska E, Banasiak W, Von Haehling S, et al. Iron status in patients with chronic heart failure. Eur Heart J 2013;34(11):827–34.

Chiang CK, Tanaka T, Inagi R, Fujita T, Nangaku M. Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin production in a HIF-dependent manner. Lab Invest 2011;91(11):1564–71.

Huang JY, Hsu CW, Yang CW, Hung CC, Huang WH. Role of anuria in the relationship between indoxyl sulfate and anemia in peritoneal dialysis patients. Ther Clin Risk Manag 2016;12:1797–803.

Bataille S, Pelletier M, Sallée M, Berland Y, McKay N, Duval A, et al. Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients. BMC Nephrol 2017;18(1):251.

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):223–5.

Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, et al. Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 2005;112(8):1121–7.

Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation 2006;113(23):2713–23.

Mozaffarian D, Nye R, Levy WC. Anemia predicts mortality in severe heart failure: The prospective randomized amlodipine survival evaluation (PRAISE). J Am Coll Cardiol 2003;41(11):1933–9.

Sîrbu O, Floria M, Dascalita P, Stoica A, Adascalitei P, Sorodoc V, et al. Anemia in heart failure - from guidelines to controversies and challenges. Anatol J Cardiol 2018;20(1):52.

Azizi M, Junot C, Ezan E, Ménard J. Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline. Clin Exp Pharmacol Physiol 2001;28(12):1066–9.

Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int 2003;63(4):1187–94.

Salzberg DJ, Karadsheh FF, Haririan A, Reddivari V, Weir MR. Specific management of anemia and hypertension in renal transplant recipients: influence of renin-angiotensin system blockade. Am J Nephrol 2014;39(1):1–7.

Vlahakos DV, Tsioufis C, Manolis A, Filippatos G, Marathias KP, Papademetriou V, et al. Inhibition of the renin-angiotensin system in the cardiorenal syndrome with anaemia: a double-edged sword. J Hypertens 2019;37(11):2145–53.

Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia. N Engl J Med 2006;20(16):2071–84.

Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 2013;368(13):1210–9.

Jankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail 2016;18(7):786–95.

JT W, JD W, PK W, JK S, KM S, MV R, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;373(22):2103–16.

Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Effects of Intensive BP Control in CKD. J Am Soc Nephrol 2017;28(9):2812–23.

Vardeny O, Claggett B, Packer M, Zile MR, Rouleau J, Swedberg K, et al. Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial. Eur J Heart Fail 2016;18(10):1228–34.

Yamada S, Inaba M. Potassium Metabolism and Management in Patients with CKD. Nutrients 2021;13(6):1751.

Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 2000;160(5):685–93.

Burnier M. Renin-Angiotensin System Blockade in Advanced Kidney Disease: Stop or Continue? Kidney Med 2020;2(3):231.

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