safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2023-11-2-231-240safetyrisk-361Research ArticleГЛАВНАЯ ТЕМА: ОТ ИССЛЕДОВАНИЙ IN VITRO К IN VIVO И КЛИНИЧЕСКИМ ИССЛЕДОВАНИЯМMAIN TOPIC: FROM IN VITRO EXPERIMENTS TO IN VIVO AND CLINICAL STUDIESКлинико-анамнестические предикторы развития сухого кашля у пациентов с кардиоваскулярной патологией на фоне приема эналаприлаClinical Signs and Medical History as Predictors of Enalapril-Associated Dry Cough in Cardiovascular Patientshttps://orcid.org/0000-0003-0227-2651СычевИ. В.SychevI. V.

Сычев Иван Витальевич

Большевистская ул., д. 68, г. Саранск, 430005

Ivan V. Sychev

68 Bolshevistskaya St., Saransk 430005, Mordovia

sychev_iv@bk.ruhttps://orcid.org/0000-0003-3278-5941ДенисенкоН. П.DenisenkoN. P.

Денисенко Наталья Павловна, канд. мед. наук

Баррикадная ул., д. 2/1, стр. 1, Москва, 125993

Natalia P. Denisenko, Cand. Sci. (Med.)

2/1/1 Barrikadnaya St., Moscow 125993

natalypilipenko3990@gmail.comhttps://orcid.org/0000-0003-3194-4410КачановаА. А.KachanovaA. A.

Качанова Анастасия Алексеевна

Баррикадная ул., д. 2/1, стр. 1, Москва, 125993

Anastasia A. Kachanova

2/1/1 Barrikadnaya St., Moscow 125993

aakachanova@yandex.ruhttps://orcid.org/0000-0003-4828-2476ЛапштаеваА. В.LapshtaevaA. V.

Лапштаева Анна Васильевна, канд. мед. наук

Большевистская ул., д. 68, г. Саранск, 430005

Anna V. Lapshtaeva, Cand. Sci. (Med.)

68 Bolshevistskaya St., Saransk 430005, Mordovia

av_lapshtaeva@mail.ruhttps://orcid.org/0000-0001-9001-1499АбдуллаевШ. П.AbdullaevSh. P.

Абдуллаев Шерзод Пардабоевич, канд. биол. наук

Баррикадная ул., д. 2/1, стр. 1, Москва, 125993

Sherzod P. Abdullaev, Cand. Sci. (Biol.)

2/1/1 Barrikadnaya St., Moscow 125993

sherzodx5@gmail.comhttps://orcid.org/0000-0002-4324-9071ГончароваЛ. Н.GoncharovaL. N.

Гончарова Людмила Никитична, д-р мед. наук

Большевистская ул., д. 68, г. Саранск, 430005

Lyudmila N. Goncharova, Dr. Sci. (Med.)

68 Bolshevistskaya St., Saransk 430005, Mordovia

glnsm@mail.ruhttps://orcid.org/0000-0002-9307-4994МирзаевК. Б.MirzaevK. B.

Мирзаев Карин Бадавиевич, д-р мед. наук

Баррикадная ул., д. 2/1, стр. 1, Москва, 125993

Karin B. Mirzaev, Dr. Sci. (Med.)

2/1/1 Barrikadnaya St., Moscow 125993

karin05doc@yandex.ruhttps://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Сычев Дмитрий Алексеевич, академик РАН, д-р мед. наук, профессор

Баррикадная ул., д. 2/1, стр. 1, Москва, 125993

Dmitry A. Sychev, Academician of the RAS, Dr. Sci. (Med.), Professor

2/1/1 Barrikadnaya St., Moscow 125993

dmitry.alex.sychev@gmail.comФедеральное государственное бюджетное образовательное учреждение высшего образования «Национальный исследовательский Мордовский государственный университет им. Н.П. Огарева»РоссияNational Research Ogarev Mordovia State UniversityRussian FederationФедеральное государственное бюджетное общеобразовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Postgraduate EducationRussian Federation202324042023112231240Copyright © Сычев И.В., Денисенко Н.П., Качанова А.А., Лапштаева А.В., Абдуллаев Ш.П., Гончарова Л.Н., Мирзаев К.Б., Сычев Д.А., 20232023Сычев И.В., Денисенко Н.П., Качанова А.А., Лапштаева А.В., Абдуллаев Ш.П., Гончарова Л.Н., Мирзаев К.Б., Сычев Д.А.Sychev I.V., Denisenko N.P., Kachanova A.A., Lapshtaeva A.V., Abdullaev S.P., Goncharova L.N., Mirzaev K.B., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/361

Ингибиторы ангиотензинпревращающего фермента (ИАПФ) являются одними из наиболее часто назначаемых и эффективных препаратов для лечения ряда кардиоваскулярных заболеваний. Согласно данным ряда исследований, у 30% пациентов, принимавших ИАПФ, развиваются нежелательные реакции, вследствие чего часто возникает необходимость отмены терапии. Наиболее частой нежелательной реакцией является сухой кашель, при этом клинико-анамнестические предикторы его развития у пациентов с кардиоваскулярной патологией изучены недостаточно.

Цель работы

Цель работы: изучение клинико-анамнестических предикторов развития кашля на фоне приема эналаприла у пациентов с кардиоваскулярной патологией.

Материалы и методы

Материалы и методы: в исследовании, проведенном в период с 2019 по 2022 г., приняли участие 224 пациента с эссенциальной артериальной гипертензией 2–3 стадий, принимавших эналаприл в дозах 10–20 мг/сут. Пациенты были разделены на две группы: 1 группа — 113 человек, у которых на фоне приема эналаприла развился кашель; 2 группа (группа контроля) — 104 человека, у которых не было выявлено развития нежелательных реакций на фоне приема эналаприла. Всем пациентам при формировании групп было проведено общеклиническое обследование, собраны данные аллергологического и фармакологического анамнеза. На основании анализа полученных данных изучена ассоциация клинико-анамнестических показателей с развитием нежелательной реакции в виде сухого кашля.

Результаты

Результаты: в группе пациентов с развитием сухого кашля на фоне приема ИАПФ достоверно чаще, чем в группе контроля, встречались лица с проявлениями лекарственной токсикодермии в анамнезе (OR=5,639, CI 2,234–14,236; χ2=15,845, р<0,001), наличием сахарного диабета 2 типа (OR=3,409, CI 1,461–7,953; χ2=8,7472, р<0,01), с отягощенной наследственностью по бронхиальной астме (OR=4,141, CI 2,066–8,299; χ2=17,417, р<0,001) и наличием тяжелых проявлений аллергических реакций у близких родственников (OR=3,714, CI 1,720–8,018; χ2=12,137, р<0,001).

Выводы

Выводы: наличие в анамнезе у пациентов наследственных заболеваний аллергического характера увеличивает вероятность развития сухого кашля при применении препаратов группы ИАПФ. Для повышения безопасности терапии ИАПФ необходимо проводить более подробный опрос пациентов с кардиоваскулярной патологией о наличии аллергических заболеваний, в том числе у кровных родственников первой степени родства.

Angiotensin-converting enzyme inhibitors (ACEIs) are among the most prescribed and effective medicinal products for the treatment of several cardiovascular diseases. According to a number of studies, 30% of patients taking ACEIs develop adverse drug reactions (ADRs), and treatment discontinuation is often required as a result. The most common ADR associated with ACEIs is a dry (non-productive) cough. Nevertheless, the clinical signs and medical history predictive of this ADR in cardiovascular patients are still understudied.

The aim of the study was to analyse the clinical signs and medical history predictive of cough in patients with cardiovascular conditions treated with enalapril.

Materials and methods

Materials and methods. The study was carried out in 2019–2022 and enrolled 224 patients with essential hypertension (grades 2 and 3) treated with enalapril at a dose of 10–20 mg/day. The patients were assigned to 2 groups: Group 1 included 113 patients with enalapril-associated cough, while Group 2 (control group) comprised 104 patients without this ADR. At screening, all the patients underwent a general examination and a check of their allergy and medication history. Using the data obtained, the authors analysed the association of the clinical signs and medical history with the ADR of interest (dry cough).

Results

Results. In contrast to the control group, the group with ACEI-associated dry cough included more patients with a history of drug-induced toxicoderma (OR=5.639, CI 2.234–14.236, χ2=15.845, and p<0.001) or type 2 diabetes mellitus (OR=3.409, CI 1.461–7.953, χ2=8.7472, and p<0.01), a family history of bronchial asthma (OR=4.141, CI 2.066–8.299, χ2=17.417, and p<0.001), and a close family history of severe allergic reactions (OR=3.714, CI 1.720– 8.018, χ2=12.137, and p<0.001).

Conclusions

Conclusions. A family history of allergy increases the probability of dry cough in patients taking ACEIs. In order to improve the safety of ACEI therapy, patients with cardiovascular conditions should be asked more detailed questions about their personal or first-degree family history of allergy.

ингибиторы ангиотензинпревращающего ферментаэналаприлсухой кашельнежелательная реакцияпредикторы нежелательных реакцийкардиоваскулярная патологияаллергологический анамнезклиническое исследованиеangiotensin-converting enzyme inhibitorsenalaprildry coughadverse drug reactionadverse drug reaction predictorscardiovascular pathologyhistory of allergiesclinical studyРабота выполнена при финансовой поддержке Министерства здравоохранения Российской Федерации. Тематика государственного задания: «Новые фармакогенетические биомаркеры безопасности фармакотерапии некоторых социально-значимых заболеваний» (ЕГИСУ НИОКТР № 121110800062-6).This study was sponsored by the Ministry of Health of the Russian Federation. It was carried out as part of publicly funded research project “New Pharmacogenetic Biomarkers of the Safety of Pharmacotherapy of Certain Socially Significant Diseases” (Unified State Information System for Accounting of Scientific Research, Experimental Design and Technological Works for Civil Purposes, No. 121110800062-6).ReferencesChan NJ, Soliman AM. Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation, and management. Ann Otol Rhinol Laryngol. 2015;124(2):89–96. https://doi.org/10.1177/0003489414543069Chan NJ, Soliman AM. Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation, and management. Ann Otol Rhinol Laryngol. 2015;124(2):89–96. https://doi.org/10.1177/0003489414543069Soo Hoo GW, Lin HK, Junaid I, Klaustermeyer WB. Angiotensin-converting enzyme inhibitor angioedema requiring admission to an intensive care unit. Am J Med. 2015;128(7):785–9. https://doi.org/10.1016/j.amjmed.2015.02.006Soo Hoo GW, Lin HK, Junaid I, Klaustermeyer WB. Angiotensin-converting enzyme inhibitor angioedema requiring admission to an intensive care unit. Am J Med. 2015;128(7):785–9. https://doi.org/10.1016/j.amjmed.2015.02.006Brugts JJ. Discontinuation of angiotensin conver ting enzyme inhibitors due to dry cough: incidence and clinical determinants. Clin Pharmacol Ther. 2019;105(3):563. https://doi.org/10.1002/cpt.1130Brugts JJ. Discontinuation of angiotensin conver ting enzyme inhibitors due to dry cough: incidence and clinical determinants. Clin Pharmacol Ther. 2019;105(3):563. https://doi.org/10.1002/cpt.1130Borghi C, Cicero AF, Agnoletti D, Fiorini G. Pathophysiology of cough with angiotensin-converting enzyme inhibitors: how to explain within-class differences? Eur J Intern Med. 2023;110:10–5. https://doi.org/10.1016/j.ejim.2023.01.005Borghi C, Cicero AF, Agnoletti D, Fiorini G. Pathophysiology of cough with angiotensin-converting enzyme inhibitors: how to explain within-class differences? Eur J Intern Med. 2023;110:10–5. https://doi.org/10.1016/j.ejim.2023.01.005Morimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF, et al. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J Eval Clin Pract. 2004;10(4):499–509. https://doi.org/10.1111/j.1365-2753.2003.00484.xMorimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF, et al. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J Eval Clin Pract. 2004;10(4):499–509. https://doi.org/10.1111/j.1365-2753.2003.00484.xNg LP, Goh PS. Incidence of discontinuation of angiotensin-converting enzyme inhibitors due to cough, in a primary healthcare centre in Singapore. Singapore Med J. 2014;55(3):146–9. https://doi.org/10.11622/smedj.2014034Ng LP, Goh PS. Incidence of discontinuation of angiotensin-converting enzyme inhibitors due to cough, in a primary healthcare centre in Singapore. Singapore Med J. 2014;55(3):146–9. https://doi.org/10.11622/smedj.2014034Nasser J, Al Aradi K, Kubra SE, Omran A. High incidence of cough among users of angiotensin-converting enzyme inhibitors. Bahrain Med Bull. 2018;40(2):97–9. https://doi.org/10.12816/0047558Nasser J, Al Aradi K, Kubra SE, Omran A. High incidence of cough among users of angiotensin-converting enzyme inhibitors. Bahrain Med Bull. 2018;40(2):97–9. https://doi.org/10.12816/0047558Jamshed F, Jaffry H, Hanif H, Kumar V, Naz U, Ahmed M, Fareed S. Demographic and clinical characteristics of patients presenting with angiotensin-converting enzyme inhibitors induced cough. Cureus. 2019;11(9):e5624. https://doi.org/10.7759/cureus.5624Jamshed F, Jaffry H, Hanif H, Kumar V, Naz U, Ahmed M, Fareed S. Demographic and clinical characteristics of patients presenting with angiotensin-converting enzyme inhibitors induced cough. Cureus. 2019;11(9):e5624. https://doi.org/10.7759/cureus.5624Lavorini F, Chellini E, Innocenti M, Campi G, Egan CG, Mogavero S, Fontana GA. A crossover randomized comparative study of zofenopril and ramipril on cough reflex and airway inflammation in healthy volunteers. Cough. 2014;10(1):7. https://doi.org/10.1186/s12997-014-0007-5Lavorini F, Chellini E, Innocenti M, Campi G, Egan CG, Mogavero S, Fontana GA. A crossover randomized comparative study of zofenopril and ramipril on cough reflex and airway inflammation in healthy volunteers. Cough. 2014;10(1):7. https://doi.org/10.1186/s12997-014-0007-5Boonyapisit W, Tresukosol D. Comparison of the incidence of imidapril and enalapril induced cough. J Med Assoc Thai. 2010;93 Suppl 1:S48–53. PMID: 20364557Boonyapisit W, Tresukosol D. Comparison of the incidence of imidapril and enalapril induced cough. J Med Assoc Thai. 2010;93 Suppl 1:S48–53. PMID: 20364557Loo HC, Osman F, Ho SL, An SY, Yong YMA, Khoo EM. Incidence of angiotensin-converting enzyme inhibitor-induced cough in a Malaysian public primary care clinic: a retrospective cohort study. Malays Fam Physician. 2022;17(1):66–70. https://doi.org/10.51866/oa.80Loo HC, Osman F, Ho SL, An SY, Yong YMA, Khoo EM. Incidence of angiotensin-converting enzyme inhibitor-induced cough in a Malaysian public primary care clinic: a retrospective cohort study. Malays Fam Physician. 2022;17(1):66–70. https://doi.org/10.51866/oa.80Liang L, Kung JY, Mitchelmore B, Gill J, Cave A, Banh HL. Angiotensin-converting enzyme inhibitor induced cough in Chinese patients: a systematic review and meta-analysis. J Pharm Pharm Sci. 2021;24:137–47. https://doi.org/10.18433/jpps31632Liang L, Kung JY, Mitchelmore B, Gill J, Cave A, Banh HL. Angiotensin-converting enzyme inhibitor induced cough in Chinese patients: a systematic review and meta-analysis. J Pharm Pharm Sci. 2021;24:137–47. https://doi.org/10.18433/jpps31632Mateti UV, Nekkanti H, Vilakkathala R, Rajakannan T, Mallayasamy S, Ramachandran P. Pattern of angiotensin-converting enzyme inhibitors induced adverse drug reactions in South Indian teaching hospital. N Am J Med Sci. 2012;4(4):185–9. https://doi.org/10.4103/1947-2714.94945Mateti UV, Nekkanti H, Vilakkathala R, Rajakannan T, Mallayasamy S, Ramachandran P. Pattern of angiotensin-converting enzyme inhibitors induced adverse drug reactions in South Indian teaching hospital. N Am J Med Sci. 2012;4(4):185–9. https://doi.org/10.4103/1947-2714.94945Olowofela AO, Isah AO. A profile of adverse effects of antihypertensive medicines in a tertiary care clinic in Nigeria. Ann Afr Med. 2017;16(3):114-119. https://doi.org/10.4103/aam.aam_6_17Olowofela AO, Isah AO. A profile of adverse effects of antihypertensive medicines in a tertiary care clinic in Nigeria. Ann Afr Med. 2017;16(3):114-119. https://doi.org/10.4103/aam.aam_6_17Schröder H. Reizhusten bei ACE-Hemmer-Einnahme [Dry cough from ACE inhibitors]. Med Monatsschr Pharm. 2005;28(9):321–2. German. PMID: 16163883Schröder H. Reizhusten bei ACE-Hemmer-Einnahme [Dry cough from ACE inhibitors]. Med Monatsschr Pharm. 2005;28(9):321–2. German. PMID: 16163883Tebha SS, Zaidi ZA, Sethar S, Virk MAA, Yousaf MN. Angiotensin converting enzyme inhibitor associated spontaneous herniation of liver mimicking a pleural mass: a case report. World J Hepatol. 2022;14(4):854–9. https://doi.org/10.4254/wjh.v14.i4.854Tebha SS, Zaidi ZA, Sethar S, Virk MAA, Yousaf MN. Angiotensin converting enzyme inhibitor associated spontaneous herniation of liver mimicking a pleural mass: a case report. World J Hepatol. 2022;14(4):854–9. https://doi.org/10.4254/wjh.v14.i4.854Trovato DA, Sousa JE, Bruetman JE, Finn BC, Young P. Fracturas costales simétricas asociadas a tos [Symmetrical rib fractures associated with chronic cough. Report of one case]. Rev Med Chil. 2018;146(3):391–3. Spanish. https://doi.org/10.4067/s0034-98872018000300391Trovato DA, Sousa JE, Bruetman JE, Finn BC, Young P. Fracturas costales simétricas asociadas a tos [Symmetrical rib fractures associated with chronic cough. Report of one case]. Rev Med Chil. 2018;146(3):391–3. Spanish. https://doi.org/10.4067/s0034-98872018000300391Pinto B, Jadhav U, Singhai P, Sadhanandham S, Shah N. ACEI-induced cough: a review of current evidence and its practical implications for optimal CV risk reduction. Indian Heart J. 2020;72(5):345–50. https://doi.org/10.1016/j.ihj.2020.08.007Pinto B, Jadhav U, Singhai P, Sadhanandham S, Shah N. ACEI-induced cough: a review of current evidence and its practical implications for optimal CV risk reduction. Indian Heart J. 2020;72(5):345–50. https://doi.org/10.1016/j.ihj.2020.08.007Fox AJ, Lalloo UG, Belvisi MG, Bernareggi M, Chung KF, Barnes PJ. Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough. Nat Med. 1996;2(7):814–7. https://doi.org/10.1038/nm0796-814Fox AJ, Lalloo UG, Belvisi MG, Bernareggi M, Chung KF, Barnes PJ. Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough. Nat Med. 1996;2(7):814–7. https://doi.org/10.1038/nm0796-814Yılmaz İ. Angiotensin-converting enzyme inhibitors induce cough. Turk Thorac J. 2019;20(1):36–42. https://doi.org/10.5152/TurkThoracJ.2018.18014Yılmaz İ. Angiotensin-converting enzyme inhibitors induce cough. Turk Thorac J. 2019;20(1):36–42. https://doi.org/10.5152/TurkThoracJ.2018.18014Fernandez-Rando M, Herrera MD, Almeida-González CV, Grilo A. Days needed for the disappearance of a cough due to the use of an angiotensin-converting enzyme inhibitor and identification of predisposing factors associated with its appearance in a clinical cohort of hypertensive patients. J Clin Pharmacol. 2021;61(5):591–7. https://doi.org/10.1002/jcph.1786Fernandez-Rando M, Herrera MD, Almeida-González CV, Grilo A. Days needed for the disappearance of a cough due to the use of an angiotensin-converting enzyme inhibitor and identification of predisposing factors associated with its appearance in a clinical cohort of hypertensive patients. J Clin Pharmacol. 2021;61(5):591–7. https://doi.org/10.1002/jcph.1786Teklay G, Gebremedhin A, Ayalew E. Prevalence of cough among patients treated with angiotensin converting enzyme inhibitors. International Journal of Pharma Sciences and Research. 2014;12(5):992–8.Teklay G, Gebremedhin A, Ayalew E. Prevalence of cough among patients treated with angiotensin converting enzyme inhibitors. International Journal of Pharma Sciences and Research. 2014;12(5):992–8.Sato A, Fukuda S. A prospective study of frequency and characteristics of cough during ACE inhibitor treatment. Clin Exp Hypertens. 2015;37(7):563–8. https://doi.org/10.3109/10641963.2015.1026040Sato A, Fukuda S. A prospective study of frequency and characteristics of cough during ACE inhibitor treatment. Clin Exp Hypertens. 2015;37(7):563–8. https://doi.org/10.3109/10641963.2015.1026040Wyskida K, Jura-Szołtys E, Smertka M, Owczarek A, Chudek J. Factors that favor the occurrence of cough in patients treated with ramipril—a pharmacoepidemiological study. Med Sci Monit. 2012;18(9):PI21–8. https://doi.org/10.12659/msm.883336Wyskida K, Jura-Szołtys E, Smertka M, Owczarek A, Chudek J. Factors that favor the occurrence of cough in patients treated with ramipril—a pharmacoepidemiological study. Med Sci Monit. 2012;18(9):PI21–8. https://doi.org/10.12659/msm.883336

The authors declare that there are no conflicts of interest present.