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39Жамият ва инновациялар -Общество и инновации -Society and innovations
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Effective influence of sacubitril/valsartan on systolic function of left ventricle in patients with heart failure and a reduced ejection fraction
Ikbol ADILOVA1, Gulnoza AKBAROVA2
Republican Scientific-Practical Center of Sports Medicine Tashkent State Stomatology Institute
ARTICLE INFO
ABSTRACT
Article history:
Received March 2021 Received in revised form 20 March 2021 Accepted 15 April 2021 Available online 20 May 2021
Keywords:
sacubitril/valsartan; neprilysin,
reduced ejection fraction, heart failure, left ventricle.
Aim: We evaluated the influence of sacubitril/valsartan on the left ventricle function and clinical status of patients with heart failure and a reduced ejection fraction.
Materials and methods: From 2018 to 2020, patients cured with 50-200 mg sacubitril/valsartan after coronary bypass grafting or coronary stenting for ischemic heart disease and HFrEF (aged 54-70 years) were enrolled in this prospective study.
Results: There was no death case. There was a female prevalence with female to male ratio of 1,7:1. the value of ejection fraction high significantly increased(p=0,035), whereas the indices of left ventricle end-diastolic volume(p=0,015) and end-diastolic volume index (p=0,022) as well as left ventricle mass index were high significantly decreased(p=0,001) that indicate the amelioration of left ventricle systolic function. Correspondingly, the clinical status of all patients improved according to New York Heart Association Class (p=0,001).
Conclusion: The post-CABG or PCI patients with HFrEF should be cured with sacubitril/valsartan basingon its implementation instruction. Nevertheless, future studies should focus on a larger cohort of post-CABG or PCI patients to compare the effectiveness and safety of sacubitril/valsartan usage raising from its adverse event in comparison to conventional therapy.
2181-1415/© 2021 in Science LLC.
This is an open access article under the Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/deed.ru)
1 Doctor of Philosophy, Republican Scientific-Practical Center of Sports Medicine, Tashkent, Uzbekistan. E-mail: ikbol.adilova@mail.ru.
2 Doctor of Philosophy, Tashkent State Stomatology Institute, Tashkent, Uzbekistan. E-mail: bakolli19@mail.ru.
Юрак етишмовчилиги ва паст фракцияли беморларда сакубитрил/валсартан чап крринча систолик функциясига эффективли таъсири
Калит сузлар:
сакубутрил/валсартан;
неприлизин,
пасайган кискариш
фракцияси,
юрак етишмовчилиги,
чап коринча.
АННОТАЦИЯ
Максад: сакубутрил/валсартаннинг юрак етишмовчилиги ва пасайган кискариш фракцияси билан булган беморларнинг чап коринчаси столик функциясига ва клиник х,олатига таъсирини бах,олаш.
Материаллар ва методлар: 2018-2020 йй. мобайнида илмий тадк;ик;отга коронар шунтлаш еки стентлашдан кейин 50-200 мг сакубитрил/валсартан билан даволанган беморлар (54-70 ёш) жалб этилди.
Натижалар: улим асорати кайд етилмади. Аёлларнинг эркакларга нисбати 1,7:1 ни ташкил етди. Чап коринча кискариш фракцияси статистик ахамиятли даражада пасайди (р=0,035). Якуний диастолик х,ажми курсаткичлари (р=0,015) ва якуний диастолик х,ажми индекси (р=0,022), шунингдек, чап коринча масса индекси статистик ахамиятли даражада камайганлиги (р=0,001) чап коринча систолик функциясини яхшилаганлигини билдиради. Х,амда, барча беморларнинг NYHA буйича клиник х,олатияхшиланди (р=0,001).
Хулоса: юрак етишмовчилиги ва юрак кискариш фракцияси паст булган беморлар коронар шунтлаш ёки стентлашдан кейин сакубитрил/валсартан билан даволаниши максадга мувофик. Бирок, келажакда тадкикотлар коронар шунтлаш еки стентлашни куздан кечирган купрок беморларда сакубитрил/валсартан самарадорлигини ва хавфсизлигини уларнинг салбий таъсиридан келиб чиккан х,олда анъанавий даво услуби билан таккослашга каратилган булиши керак.
Эффективное влияние сакубитрил/валсартана на систолическую функцию левого желудочка у пациентов с сердечной недостаточностью и низкой фракцией выброса
Ключевые слова:
сакубитрил/валсартан;
неприлизин,
сниженная фракция
выброса,
сердечная
недостаточность,
левый желудочек.
АННОТАЦИЯ
Цель: оценка влияния сакубитрил/валсартана на функцию левого желудочка и клинический статус пациентов с сердечной недостаточностью и сниженной фракцией выброса.
Материалы и методы: с 2018 по 2020 гг. в проспективное исследование были включены пациенты, излечившиеся с помощью сакубитрил/валсартана в дозе 50-200 мг после АКШ или ЧКВ по поводу ишемической болезни сердца и сердечной недостаточности с низкой фракцией выброса (в возрасте 54-70 лет).
Результаты: летальный исход не был отмечен. Соотношение женщин и мужчин составило 1,7: 1. Значение высокой фракции выброса достоверно увеличилось (p = 0,035), тогда как показатели конечного диастолического объема левого желудочка (p = 0,015) и индекса конечного диастолического объема (p = 0,022), а также индекса массы левого желудочка статистически значимо уменьшились (p = 0,001), что свидетельствует об улучшении систолической функции левого желудочка. Соответственно, клинический статус всех пациентов улучшился по классу NYHA (p = 0,001).
Заключение: пациенты с сердечной недостаточностью и сниженной фракцией выброса после АКШ или ЧКВ должны лечиться сакубитрил/валсартаном в соответствии с инструкциями по его применению. Тем не менее, будущие исследования должны быть сосредоточены на более широкой когорте пациентов, перенесших АКШ или ЧКВ, чтобы сравнить эффективность и безопасность применения сакубитрил/валсартана в отношении его побочных действий в сравнение с традиционной терапией.
INTRODUCTION
Approximately 7% among all leading causes of the overall morbidity in Uzbekistan attributed to chronic heart failure [1]. As known, over the last 20 years the rate of morbidity and mortality is diminished in patients with heart failure with reduced ejection fraction (HFrEF) by means of medications targeted the renin-angiotensin-aldosterone system [2, 3]. As previously reported, several efforts to potentially benefit patients with HFrEF due to the rise of the activity of natriuretic peptides (NPs) have failed until a large (n=8442 patients), phase III, randomized, controlled clinical trial (PARADIGM-HF) which highlighted the advantageous results of sacubitril/valsartan regarding decrease the risk of cardiovascular death and hospitalization for heart failure by 20% and 16% less risk for death from any cause as compared with enalapril (p<0,001) [4]. As shown in figure 1, sacubitril/valsartan (formerly known as LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that simultaneously suppresses RAAS activation through blockade of angiotensin II type 1 receptors and enhances vasoactive peptides including NPs through inhibition of neprilysin, the enzyme responsible for their degradation [5, 6]. As a result, ARNI combined with angiotensin II receptor antagonist contribute to the neurohormonal balanced influence on vasodilation and vasoconstriction. Nevertheless, the influence of sacubitril/valsartan on systolic function of left ventricle (LV) after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) less studied that we aimed at handling with it.
Mechanism of action of LCZ696
Fig 1. A mechanism of the balanced effect of sacubitril/valsartan on vasodilation and
vasoconstriction.
MATERIALS AND METHODS
A prospective observational study conducted on 30 patients after coronary bypass grafting or coronary stenting for ischemic heart disease and HFrEF, aged between 54 and 70 years, who were investigated in out-patient department ofRepublican Scientific-Practical Center of Sports Medicineand treated with 50-200 mg sacubitril/valsartan (YuperioTM; Novartis Pharma services, Switzerland)between December 2018 and December 2020. The inclusion criterion of HFrEF patients was the post-CABG or coronary stenting states. The informed consent was obtained from the patient's next of kin. Patient demographics are given in Table 1.
Table 1.
Patient demographics (n=30).
Variable n (%) or mean ± SD
Age (years) 63,0+4,72
Sex (F/M) 19/11(63,6/36,4)
Hypertension 27 (90,9)
Postinfarction cardiosclerosis 22 (72,7)
Diabetes 16(54,5)
*Post CABG 13 (43,3)
*PostCS 17(56,7)
Mitral regurgitation I degree 13(43,3)
Mitral regurgitation II degree 3(10,0)
*RBBB 11 (36,4)
*CABBG - coronary artery bypass grafting, * CS - coronary stenting, *RBBBB - right bundle branch block.
Statistical analysis. Data were processed by using SPSS 19.0 statistical analysis software. The quantitative data were expressed as the mean and standard deviation (SD), respectively.Continuous variables were compared using t test and the rank-sum tests. P<0,05 was considered statistically significant, whereas P<0,001 was highly significant.
RESULTS
There was a female prevalence with female to male ratio of 1,7:1. A mean follow-up period was 2,1±0,5 years. At the final follow-up examination, neither readmission to clinic due to exacerbation of heart failure nor death case was registered. As seen in table 2, the echocardiographic signs of mild and moderate ischemic mitral regurgitation were high significantly disappeared (p=0,001). Correspondingly, the value of ejection fraction high significantly raised (p=0,035), whereas the indices of left ventricle end-diastolic volume(p=0,015) and end-diastolic volume index (p=0,022) as well as left ventricle mass index were high significantly dropped (p=0,001) that indicate the amelioration of left ventricle contractility. As a result, the clinical status of all patients improved according to New York Heart Association Class (p=0,001).
Table 2.
Comparative echocardiographic results of left ventricle function and clinical status before and after sacubitril/valsartan introduction (n=30).
Parameters Before medication After medication P
Secondary mitral regurgitation, n (%) Mild 18 (60,0) 0 0,001
Moderate 14 (4,67) 0 0,001
Ejection fraction (%) 42,54±5,02 51,54±4,41 0,035
Left ventricle contractility-hypokinesia, n (%) 19(63,3) 2(6,7) 0,001
Left ventricle end-diastolic volume, ml 200,72±50,66 114,75±22,45 0,015
Left ventricle end-diastolic volume index, ml/m2 115,84±2,93 88,93±2,13 0,022
Left ventricle mass index, gr/m2 123,03±48,46 95,27±25,41 0,001
*NYHA class, n (%) I 1 (3,3) 0 0,001
II 27 (90) 10 (33,3) 0,001
III 2 (6,6) 0 0,001
*NYHA - New York Heart Association. DISCUSSION
As previously reported, chronic heart failure resulting in depressed ejection fraction of left ventricle has been considered as a frequent cause of death not only in older but also in young patients [7-10].
Of particular interest, a randomized, controlled clinical trial (PARADIGM-HF) showed that 21 (0,2%) patients of all 8442 needed treatment with sacubitril/valsartan instead of enalapril for 27 months to prevent one death from a cardiovascular cause or hospitalization for HF. Fonarow et al. reported that approximately 28,484 deaths (range 18,230-41,017) could be prevented yearly with optimal usage of ARNI/ARBs therapy instead of ACEIs/ARBs that may accelerate more implementation of ARNI/ARBs [11].
Accordingly, the 2017 update of the American College of Cardiology/ American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) guideline for HF management included ARNI/ARBs, along with ACEIs and ARBs, as a treatment to reduce mortality and morbidity in HFrEF [11, 12].
The results of De Vecchis et al. retrospective study demonstrated the reduction of mortality rate at 6 months (OR 0,14; 95% CI 0,04-0,50) and HF hospitalization (OR 0,03; 95% CI 0,01-0,14) in patients treated with sacubitril/valsartan versus conventional therapy [13]. Furthermore, according to some studies' data, adverse events profile for sacubitril/valsartan is similar to that of ACEIs/ARBs [13, 14].
To the best of our knowledge, previous studies are scarce regarding the evaluation of sacubitril/valsartan influence on left ventricle geometry and function in HFrEF patients after CABG or PCI and mostly have focused on ischemic heart disease but non-operated patients. Thus, our goal in this study is to facilitate research on the aforementioned effect of sacubitril/valsartan treatment.
Though competing in the past, conservative therapy with sacubitril/valsartan should not be opposed to other treatment strategy comprising ACE inhibitor usage [15, 16]. This study was conducted to better define the place of sacubitril/valsartan introduction in the armamentarium to treat patients with chronic heart failure after coronary bypass grafting or stenting. As identified in this study, the post-CABG or PCI patients with depressed ejection fraction are considered as appropriate candidates for the abovementioned therapy.
The results of our experience are coexistent with previous studies regarding the effect of sacubitril/valsartan implementation on left ventricle systolic function and absence of both readmissions due to clinical worsening and death.
CONCLUSION
To summarize, sacubitril/valsartan may reduce the rate of rehospitalization due to the clinical deterioration as well as death rate in these candidates. Thus, our findings suggest that the post-CABG or PCI patients with HFrEF should be placed on sacubitril/valsartan treatment according to its implementation instruction. Nevertheless, confirmation of the clinical usefulness and safety of latter treatment concerning it adverse events compared to ACEIs/ARBs requires further studies in a larger cohort of post-CABG or PCI patients.
REFERENCES:
1. Stozharova N.K., MMD, Sadullaeva K.A., Sharipova S.A. Analysis of prevalence of the cardiovascular diseases in the population of Uzbekistan. Young Scientist. 2015. 90(10).
2. Adilova I.G., Abdurakhmanov M.M., Abdurakhmanov Z.M. Влияние возрастного фактора и возраст-ассоциированных предикторов на отдалённые результаты коронарного [Influence of age factor and age-associated predictors on remote results of coronary artery bypass grafting]. AngiolSosudKhir. 2020;26(4):161-167. Russian. doi: 10.33529/ANGI02020414. PMID: 33332319.
3. Adilova I.G., Salomova A.F., Abdurakhmanov Z.M. Age Factor Influencing on Patients Subjected to Coronary Artery Bypass Grafting. J AngiolVasc Surg. 2020;5(1):038. doi: 10.24966/AVS-7397/100038.
4. Mc. Murray J.J., Packer M, Desai A.S., Gong J, Lefkowitz M.P., Rizkala A.R., Rouleau J.L., Shi V.C., Solomon S.D., Swedberg K, Zile M.R., PARADIGM-HF Investigators
iMlSf 1РПГР
Ull lv"'" Жамият ва инновациялар - Общество и инновации - Society and innovations
Special Issue - 4 (2021) / ISSN 2181-1415
and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. NEngl J Med 2014. - 371. - PP. 993-1004.
5. Wachter R, Senni M, Belohlavek J, Butylin D, Noe A, Pascual-Figal D, TRANSITION investigators. Initiation of sacubitril / valsartan in hospitalized patients with heart failure with reduced ejection fraction after hemodynamic stabilization: primary results of the TRANSITION study. Presented at: European Society ofCardiology Congress; August 25, 2018; Munich, Germany.
6. Abdurakhmanov Z.M., & Yemets I.N. Long-term outcomes of aortic valve repair in children with congenital heart disease and their predictors. Russian Journal of Cardiology. 2020;25(8): 131-138. doi:10.15829/1560-4071-2020-3971.
7. Mozaffarian D, Benjamin EJ, Go AS et al. Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation. 2015;131(4):29-322.
8. Khder Y, Shi V, McMurray JJV, Lefkowitz MP. Sacubitril/Valsartan (LCZ696) in Heart Failure. HandbExpPharmacol. 2017;243:133-165. doi: 10.1007/164_2016_77. PMID: 28004291.
9. Ахмедов Л.А., Абдурахманов M.M, Сафаров Н.Ш., Абдурахманов З.М. Особенности клинического течения острого инфаркта у больных молодого возраста. Вестник врача. 2011; 3: 46-50.
10. Аляви А.А., Худойбергенов Ш.А., Ахмедов Л.А., Абдурахманов З.М., Абдуллаева М.А. Факторы риска острого коронарного синдрома у больных молодого и пожилого возраста. Вестник врача. 2011; 3: 39-42.
11. Fonarow G.C., Hernandez A.F., Solomon S.D., Yancy C.W. Potential mortality reduction with optimal implementation of angiotensin receptor neprilysin inhibitor therapy in heart failure. JAMA Cardiol. 2016; 1:7 14-717. https://doi.org/ 10.1001/jamacardio.2016.1724.
12. Yancy C.W., Jessup M, Bozkurt B, Butler J, Casey D.E. Jr, Colvin M.M., Drazner M.H., Filippatos G.S, Fonarow G.C., Givertz M.M., Hollenberg S.M., Lindenfeld J.A., Masoudi F.A., Mc Bride P.E., Peterson PN, Stevenson LW, Westlake C. 2017 ACC/ AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017; 136: 137-161. https://doi.org/10.1161/CIR.0000000000000509.
13. De Vecchis R, Ariano C, Di Biase G, Noutsias M. (2018) Sacubitril/ valsartan for heart failure with reduced left ventricular ejection fraction: a retrospective cohort study. Herz. https://doi.org/10.1007/s00059-00017-04671-00051.
14. Entresto (sacubitril and valsartan) [prescribing information] (2017). Novartis Pharmaceuticals Corporation, East Hanover, NJ.
15. Ахмедов Л.А., Хамроев Э.Э., Мухидов У.Р., Бахронов Р.Р., Фозилова Х.А., Алиев Ж.С., Абдурахманов З.М. Влияние раннего применения ингибиторов ангиотензинпревращающего фермента на ремоделирование ЛЖ у больных, перенесших инфаркт миокарда. Журнал теоретической и клинической медицины. 2011; 6: 29-32.
16. Абдурахманов М.М., Мусоев Т.Я., Абдурахманов З.М., Яхёева Ф.О. Оптимизация лечебной тактики при рецидиве стенокардии после реваскуляризации миокарда. Журнал теоретической и клинической медицины. 2016; 3: 36-38.
