Статья
Перспективы применения препарата валсартан+сакубитрил при гипертоническом сердце
Течение артериальной гипертонии часто осложняется развитием гипертрофии левого желудочка (или гипертонического сердца (ГС). Основным “коридором” естественного течения ГС является развитие сердечной недостаточности с сохранённой фракцией выброса (СНсФВ). При СНсФВ значительно снижается биодоступность натрийуретических пептидов (НУП), в результате чего ослабевает активность внутриклеточной сигнальной оси цГМФ-PKG, играющей ключевую роль в поддержании нормальной диастолической функции. Повысить активность этой оси можно с помощью ингибитора неприлизина сакубитрила. При СНсФВ наибольшей эффективности от препарата валсартан+сакубитрил (В+С) следует ожидать у пациентов с тяжёлой концентрической гипертрофией левого желудочка, имеющих максимально выраженный синдром “дефицита НУП”. Препарат В+С обладает чётким гипотензивным эффектом, вызывает реверсию гипертрофии и фиброза левого желудочка. Поскольку для СНсФВ до сих пор не найдено эффективных средств лечения, основным принципом лечения ГС должно являться предотвращение прогрессии диастолической дисфункции, что оправдывает применение В+С начиная с ранних/бессимптомных стадий ГС.
1. Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet. 2015;386(9995):801-12. doi:10.1016/S0140-6736(14)61468-9.
2. Schmieder RE, Messerli FH. Hypertension and the heart. J Hum Hypertens. 2000;14(10-11):597-604. doi:10.1038/sj.jhh.1001044.
3. Seliger SL, de Lemos J, Neeland IJ, et al. Older Adults, “Malignant” Left Ventricular Hypertrophy, and Associated Cardiac-Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular Health Study). JACC Heart Fail. 2015;3(6):445-55. doi:10.1016/j.jchf.2014.12.018.
4. Verdecchia P, Angeli F, Borgioni C, et al. Changes in cardiovascular risk by reduction of left ventricular mass in hypertension: a meta-analysis. Am J Hypertens. 2003;16(11 Pt 1):895-9. doi:10.1016/s0895-7061(03)01018-5.
5. Овчинников А. Г., Потехина А. В., Ожерельева М. В., Агеев Ф. Т. Дисфункция левого желудочка при гипертоническом сердце: современный взгляд на патогенез и лечение. Кардиология. 2017;57(2S):367-82. doi:10.18087/cardio.2393.
6. Díez J, Frohlich ED. A translational approach to hypertensive heart disease. Hypertension. 2010;55(1):1-8. doi:10.1161/HYPERTENSIONAHA.109.141887.
7. Soliman EZ, Ambrosius WT, Cushman WC, et al. Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial). Circulation. 2017;136(5):440-50. doi:10.1161/CIRCULATIONAHA.117.028441.
8. Dahlof B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies. Am J Hypertens. 1992;5(2):95-110. doi:10.1093/ajh/5.2.95.
9. Heckbert SR, Post W, Pearson GD, et al. Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: the Multiethnic Study of Atherosclerosis. J Am Coll Cardiol. 2006;48(11):2285-92. doi:10.1016/j.jacc.2006.03.072.
10. Dries DL, Victor RG, Rame JE, et al. Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension. Circulation. 2005;112(16):2403-10. doi:10.1161/CIRCULATIONAHA.105.568881.
11. Chahal NS, Lim TK, Jain P, et al. New insights into the relationship of left ventricular geometry and left ventricular mass with cardiac function: A population study of hypertensive subjects. Eur Heart J. 2010;31(5):588-94. doi:10.1093/eurheartj/ehp490.
12. Timmermans PB, Wong PC, Chiu AT, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45(2):205-51.
13. Dzau VJ. Tissue renin-angiotensin system in myocardial hypertrophy and failure. Arch Intern Med. 1993;153(8):937-42.
14. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation. 1991;83(6):1849-65. doi:10.1161/01.cir.83.6.1849.
15. Drazner MH. The progression of hypertensive heart disease. Circulation. 2011;123(3):327-34. doi:10.1161/CIRCULATIONAHA.108.845792.
16. Meerson FZ. Compensatory hyperfunction of the heart and cardiac insufficiency. Circ Res. 1962;10:250-8. doi:10.1161/01.res.10.3.250.
17. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E. Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci U S A. 1982;79(10):3310-4. doi:10.1073/pnas.79.10.3310.
18. Rapaport E. Natural history of aortic and mitral valve disease. Am J Cardiol. 1975;35(2):221-7. doi:10.1016/0002-9149(75)90005-3.
19. Spirito P, Maron BJ, Bonow RO, Epstein SE. Occurrence and significance of progressive left ventricular wall thinning and relative cavity dilatation in hypertrophic cardiomyopathy. Am J Cardiol. 1987;60(1):123-9. doi:10.1016/0002-9149(87)90998-2.
20. Rame JE, Ramilo M, Spencer N, et al. Development of a depressed left ventricular ejection fraction in patients with left ventricular hypertrophy and a normal ejection fraction. Am J Cardiol. 2004;93(2):234-7. doi:10.1016/j.amjcard.2003.09.050.
21. Krishnamoorthy A, Brown T, Ayers CR, et al. Progression from normal to reduced left ventricular ejection fraction in patients with concentric left ventricular hypertrophy after longterm follow-up. Am J Cardiol. 2011;108(7):997-1001. doi:10.1016/j.amjcard.2011.05.037.
22. Ovchinnikov AG, Ojerelyeva MV, Ageev FT. Hypertensive left ventricular hypertrophy is a risk factor for the development of a HFpEF but not a depressed left ventricular ejection fraction within eight years. Eur J Heart Fail. 2017;19(Suppl 1):328. doi:10.1002/ejhf.832.
23. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. New Engl J Med. 2019;381(17):1609-20. doi:10.1056/NEJMoa1908655.
24. Steinberg BA, Zhao X, Heidenreich PA, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126(1):65-75. doi:10.1161/CIRCULATIONAHA.111.080770.
25. Weber KT, Sun Y, Campbell SE. Structural remodelling of the heart by fibrous tissue: role of circulating hormones and locally produced peptides. Eur Heart J. 1995;16(Suppl N):12-8. doi:10.1093/eurheartj/16.suppl_n.12.
26. Овчинников А. Г., Ожерельева М. В., Масенко В.П., Агеев Ф.Т. Структурно-функциональные особенности течения компенсированного гипертонического сердца и факторы его неблагоприятного прогноза. Сердце. 2017;16:185-96.
27. Ovchinnikov AG, Arefieva TI, Potekhina AV, et al. The molecular and cellular mechanisms associated with a microvascular inflammation in the pathogenesis of heart failure with preserved ejection fraction. Acta Naturae. 2020;12:40-51. doi:10.32607/actanaturae.10990.
28. Glezeva N, Baugh JA. Role of inflammation in the pathogenesis of heart failure with preserved ejection fraction and its potential as a therapeutic target. Heart Fail Rev. 2014;19(5):681-94. doi:10.1007/s10741-013-9405-8.
29. Colliva A, Braga L, Giacca M, Zacchigna S. Endothelial cell-cardiomyocyte crosstalk in heart development and disease. J Physiol. 2019;598(14):2923-39. doi:10.1113/JP276758.
30. LeWinter MM, Granzier HL. Cardiac titin and heart disease. J Cardiovasc Pharmacol. 2014;63(3):207-12. doi:10.1097/FJC.0000000000000007.
31. van Heerebeek L, Hamdani N, Falcao-Pires I, et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation. 2012;126(7):830-9. doi:10.1161/CIRCULATIONAHA.111.076075.
32. Franssen C, Chen S, Unger A, et al. Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction. JACC Heart Fail. 2016;4(4):312-24. doi:10.1016/j.jchf.2015.10.007.
33. Westermann D, Lindner D, Kasner M, et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail. 2011;4(1):44-52. doi:10.1161/CIRCHEARTFAILURE.109.931451.
34. Lugnier C, Meyer A, Charloux A, et al. The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure. J Clin Med. 2019;8(10):1746. doi:10.3390/jcm8101746.
35. Francis GS. Vasoactive hormone systems. In: Poole-Wilson PA, Colucci WS, Massie BM, Chatterjee K, Coats AJS, eds. Heart Failure: Scientific Principles and Clinical Practice. New York, NY: Churchill Livingstone; 1997:215-34.
36. Yan W, Wu F, Morser J, Wu Q. Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Pro Nat Aca Sci. 2000;97(15):8525-9. doi:10.1073/pnas.150149097.
37. Gaggin H, Mohammed A, Bhardwai A, et al. Heart failure outcomes and benefits of NT-proBNP-guided management in the elderly: results from the prospective, randomized ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study. J Card Fail. 2012;18(8):626-34. doi:10.1016/j.cardfail.2012.05.005.
38. Huntley BK, Sandberg SM, Heublein DM, et al. ProBNP-1-108 processing and degradation in human heart failure. Circulation Heart Failure. 2015;8:89-97. doi:10.1161/CIRCHEARTFAILURE.114.001174.
39. Ibebuogu UN, Gladysheva IP, Houng AK, Reed GL. Decompensated heart failure is associated with reduced corin levels and decreased cleavage of pro-atrial natriuretic peptide. Circ Heart Fail. 2011;4(2):114-20. doi:10.1161/CIRCHEARTFAILURE.109.895581.
40. Chen HH. Heart Failure. A State of Brain Natriuretic Peptide Deficiency or Resistance or Both! J Am Coll Cardiol. 2007;49(10):1089-91. doi:10.1016/j.jacc.2006.12.013.
41. Martinez-Rumayor A, Richard AM, Burnett JC, Januzzi JC. Biology of the natriuretic peptides. The Am J Cardiol. 2008;101(3A):3-8. doi:10.1016/j.amjcard.2007.11.012.
42. Ibrahim NE, McCarthy CP, Shrestha S, et al. Effect of Neprilysin Inhibition on Various Natriuretic Peptide Assays. J Am Coll Cardiol. 2019;73(11):1273-84. doi:10.1016/j.jacc.2018.12.063.
43. Shah SJ, Kitzman DW, Borlaug BA, et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation. 2016;134(1):73-90. doi:10.1161/CIRCULATIONAHA.116.021884.
44. Madamanchi C, Alhosaini H, Sumida A, Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. Int J Card. 2014;176(3):611-7. doi:10.1016/j.ijcard.2014.08.007.
45. Buckley LF, Canada JM, Del Buono MG, et al. Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction. ESC Heart Fail. 2018;5(2):372-8. doi:10.1002/ehf2.12235.
46. Obokata M, Reddy YNV, Pislaru SV, et al. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017;136(1):6-19. doi:10.1161/CIRCULATIONAHA.116.026807.
47. Pieske B, Tschope C, de Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J. 2019;40(40):3297-317. doi:10.1093/eurheartj/ehz641.
48. Nielsen PM, Grimm D, Wehland M, et al. The combination of valsartan and sacubitril in the treatment of hypertension and heart failure — an update. Basic Clin Pharmacol Toxicol. 2018;122:9-18. doi:10.1111/bcpt.12912.
49. Ando SI, Rahman MA, Butler GC, et al. Comparison of candoxatril and atrial natriuretic factor in healthy men: Effects on hemodynamics, sympathetic activity, heart rate variability, and endothelin. Hypertension. 1995;26(6):1160-6. doi:10.1161/01.hyp.26.6.1160.
50. Supasyndh O, Wang J, Hafeez K, et al. Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (65 Years) With Systolic Hypertension. Am J Hypertens. 2017;30(12):1163-9. doi:10.1093/ajh/hpx111.
51. Suematsu Y, Miura S-I, Goto M, et al. LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice. Eur J Heart Fail. 2016;18(4):386-93. doi:10.1002/ejhf.474.
52. Cunningham JW, Claggett BL, O'Meara E, et al. Effect of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFpEF. J Am Coll Cardiol. 2020;76(5):503-14. doi:10.1016/j.jacc.2020.05.072.
53. Zhang H, Liu G, Zhou W, et al. Neprilysin Inhibitor-Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice. Scientific Reports. 2019;9:1-7. doi:10.1038/s41598-019-42994-1.
54. Cheung DG, Aizenberg D, Gorbunov V, et al. Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, doubleblind, 8-week study. J Clin Hypertens (Greenwich). 2018;20(1):150-8. doi:10.1111/jch.13153.
55. Ruilope LM, Dukat A, Bohm M, et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, doubleblind, placebo-controlled, active comparator study. Lancet. 2010;375(9722):1255-66. doi:10.1016/S0140-6736(09)61966-8.
56. Kario K, Sun N, Chiang FT, et al. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, doubleblind, placebo-controlled study. Hypertension. 2014;63(4):698-705. doi:10.1161/HYPERTENSIONAHA.113.02002.
57. Zhao Y, Yu H, Zhao X, et al. The effects of LCZ696 in patients with hypertension compared with angiotensin receptor blockers: a meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol Ther. 2017;22(5):447-57. doi:10.1177/1074248417693379.
58. Wang JG, Yukisada K, Sibulo A Jr, et al. Efficacy and safety of sacubitril/valsartan (LCZ696) add-on to amlodipine in Asian patients with systolic hypertension uncontrolled with amlodipine monotherapy. J Hypertens. 2017;35(4):877-85. doi:10.1097/HJH.0000000000001219.
59. Williams B, Cockcroft JR, Kario K, et al. Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study. Hypertension. 2017;69(3):411-20. doi:10.1161/HYPERTENSIONAHA.116.08556.
60. Schmieder RE, Wagner F, Mayr M, et al. The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study. Eur Heart J. 2017;38(44):3308-17. doi:10.1093/eurheartj/ehx525.
61. Gvozdeva AD, Ovchinnikov AG, Blankova ZN, et al. Angiotensin-neprilysin inhibition in HFpEF and advanced left ventricular hypertrophy: The rationale, design, and preliminary results of a randomized open-label pilot study. Eur J Heart Fail. 2021;23(Suppl 1):in press.
62. Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial. Lancet. 2012;380(9851):1387-95. doi:10.1016/S0140-6736(12)61227-6.
63. McMurray JJV, Jackson AM, Lam CSP, et al. Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF. Circulation. 2020;141(5):338-51. doi:10.1161/CIRCULATIONAHA.119.044491.
64. Solomon SD, Vaduganathan M, Claggett BL, et al. Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. Circulation. 2020;141:352-61. doi:10.1161/CIRCULATIONAHA.119.044586.
65. Mc Causland FR, Lefkowitz MP, Claggett B, et al. Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction. Circulation. 2020;142(13):1236-45. doi:10.1161/CIRCULATIONAHA.120.047643.
66. Stiles S. FDA Expands Sacubitril/Valsartan Indication to Embrace Some HFpEF. https://www.medscape.com/viewarticle/945936.
67. Packer M, Kitzman DW. Obesity-Related Heart Failure With a Preserved Ejection Fraction: The Mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2. JACC:Heart Fail. 2018;6(8):633-9. doi:10.1016/j.jchf.2018.01.009.
68. Packer M, McMurray JJ, Desai AS, et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015;131(1):54-61. doi:10.1161/CIRCULATIONAHA.114.013748.
69. Myhre PL, Vaduganathan M, Claggett B, et al. B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial. J Am Coll Cardiol. 2019;73(11):1264-72. doi:10.1016/j.jacc.2019.01.018.
70. Zile MR, Claggett BL, Prescott MF, et al. Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol. 2016;68(22):2425-36. doi:10.1016/j.jacc.2016.09.931.