醛固酮受体拮抗剂在难治性高血压中的临床研究进展

摘要/Abstract

摘要： 难治性高血压病因复杂，水钠潴留、肾素-血管紧张素-醛固酮系统激活、交感神经系统活性增强是其重要的发病机制。近年的研究发现，在难治性高血压基础治疗上添加小剂量醛固酮受体拮抗剂能有效控制血压，保护靶器官，改善预后。现就醛固酮受体拮抗剂在难治性高血压中的临床研究作一综述。

关键词: font-size:medium, ">醛固酮受体拮抗剂；难治性高血压；螺内酯；依普利酮

Abstract: The etiology of resistant hypertension is complex, and its important pathogenesis is water and sodium retention,activation of the renin-angiotensin-aldosterone system,and enhanced sympathetic nervous system activity. In recent years, it has been found that adding low-dose aldosterone receptor antagonist to the basic treatment of resistant hypertension can effectively control blood pressure, protect target organs and improve prognosis. This article reviews the clinical research of aldosterone receptor antagonists in resistant hypertension.

Key words: Aldosterone receptor antagonist, Resistant hypertension, Spironolactone, Eplerenone

中图分类号:

张平, 高存州, 邹婧. 醛固酮受体拮抗剂在难治性高血压中的临床研究进展[J]. 中国药物评价, 2022, 39(1): 48-53.

ZHANG Ping, GAO Cun-zhou, ZOU Jing. Clinical Research Progress of Aldosterone Receptor Antagonists in Resistant Hypertension[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2022, 39(1): 48-53.

参考文献

[1]Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015[J]. The lancet,2016,388(10053):1659-1724.
     [2]Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients[J].Circulation,2012,125(13):1635-1642.
     [3]Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association[J].Hypertension,2018, 72(5):e53-e90.
     [4]中国高血压防治指南2018年修订版[J].心脑血管病防治,2019,19(1):1-44.
     [5]Calhoun DA,Booth JN,Oparil S,et al. Lackland,George Howard,Monika M. Safford,Paul Muntner. Refractory Hypertension: Determination of Prevalence, Risk Factors, and Comorbidities in a Large, Population-Based Cohort[J]. Hypertension,2014,63(3):451.
     [6]Dudenbostel T, Acelajado MC, Pisoni R, et al. Refractory hypertension: evidence of heightened sympathetic activity as a cause of antihypertensive treatment failure[J]. Hypertension, 2015, 66(1): 126-133.
     [7]Lotufo PA, Pereira AC, Vasconcellos PS, et al. Resistant hypertension: risk factors, subclinical atherosclerosis, and comorbidities among adults—The Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil)[J]. The Journal of Clinical Hypertension,2015,17(1):74-80.
     [8]Sim JJ, Bhandari SK, Shi J, et al. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system[J].Mayo Clinic Proceedings，2013,88(10):1099-1107.
     [9]Ma W, Zhang Y. Low rate of resistant hypertension in Chinese patients with hypertension: an analysis of the HOT-CHINA study[J]. Journal of Hypertension,2013,31(12):2386.
     [10]Cao G, Chen C, Lin Q, et al. Prevalence, clinical characteristics and echocardiography parameters of non-resistant, resistant and refractory hypertension in Chinese[J]. Postgraduate Medicine, 2017,129(2):187-192.
     [11]Hwang AY, Dietrich E, Pepine C J, et al. Resistant hypertension: mechanisms and treatment[J]. Current Hypertension Reports,2017,19(7）:1-11.
     [12]Feng W, Dell′Italia LJ, Sanders PW. Novel paradigms of salt and hypertension[J]. Journal of the American Society of Nephrology,2017,28(5):1362-1369.
     [13]Thomas G, Xie D, Chen HY, et al. Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: report from the Chronic Renal Insufficiency Cohort Study[J]. Hypertension,2016,67(2):387-396.
     [14]Le Jemtel TH, Richardson W, Samson R, et al. Pathophysiology and potential non-pharmacologic treatments of obesity or kidney disease associated refractory hypertension[J]. Current hypertension reports, 2017,19(2):18.
     [15]Hall JE, do Carmo JM, da Silva AA, et al. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms[J]. Circulation Research,2015,116(6):991-1006.
     [16]Te Riet L, van Esch JHM, Roks AJM, et al. Hypertension: renin-angiotensin-aldosterone system alterations[J]. Circulation Research,2015,116(6):960-975.
     [17]Shimosawa T. Salt, the renin-angiotensin-aldosterone system and resistant hypertension[J]. Hypertension Research,2013,36(8):657-660.
     [18]Siddiqui M, Calhoun DA. Refractory versus resistant hypertension[J]. Curr Opin Nephrol Hypertens,2017,26(1):14-19.
     [19]Judd EK, Calhoun DA, Warnock DG. Pathophysiology and treatment of resistant hypertension: the role of aldosterone and amiloride-sensitive sodium channels[J].Seminars in Nephrology,2014,34(5):532-539.
     [20]Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension[J]. Circulation research,2015,116(6):976-990.
     [21]Thomas P, Dasgupta I. The role of the kidney and the sympathetic nervous system in hypertension[J]. Pediatric nephrology,2015,30(4):549-560.
     [22]Salles GF, Ribeiro FM, Guimares G M, et al. A reduced heart rate variability is independently associated with a blunted nocturnal blood pressure fall in patients with resistant hypertension[J]. Journal of Hypertension,2014,32(3):644-651.
     [23]Humphrey JD, Harrison DG, Figueroa CA, et al. Central artery stiffness in hypertension and aging: a problem with cause and consequence[J].Circulation research,2016,118(3): 379-381.
     [24]Sharman JE, Boutouyrie P, Laurent S. Arterial (aortic) stiffness in patients with resistant hypertension: from assessment to treatment[J].Current Hypertension Reports,2017,19(1):2.
     [25]Koenig J B, Jaffe I Z. Direct role for smooth muscle cell mineralocorticoid receptors in vascular remodeling: novel mechanisms and clinical implications[J].Current Hypertension Reports,2014,16(5):427.
     [26]Stiefel P, Vallejo-Vaz A J, Morillo SG, et al. Role of the Renin-Angiotensin System and Aldosterone on Cardiometabolic Syndrome[J]. ypertension,2011,22:24.
     [27]Min SH, Kim SH, Jeong IK, et al. Independent association of serum aldosterone level with metabolic syndrome and insulin resistance in Korean adults[J]. Korean Circulation Journal,2018,48(3):198.
     [28]Qi Y, Aranda JM, Rodriguez V, et al. Impact of antibiotics on arterial blood pressure in a patient with resistant hypertension-A case report[J].nternational Journal of Cardiology,2015,201: 157-158.
     [29]汪羚利,李昭屏.盐皮质激素受体拮抗剂在难治性高血压中的应用现状[J].心血管病学进展,2020,41(10):1026-1030.
     [30]申庆荣,李刚.螺内酯治疗难治性高血压的研究进展[J].中国医院药学杂志,2016,36(23):2126-2131.
     [31]Williams B, MacDonald T M, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial[J].The Lancet,2015,386(10008):2059-2068.
     [32]Krieger EM, Drager LF, Giorgi DMA, et al. Spironolactone versus clonidine as a fourth-drug therapy for resistant hypertension: the ReHOT randomized study (Resistant Hypertension Optimal Treatment)[J].Hypertension,2018,71(4):681-690.
     [33]Zhao D, Liu H, Dong P, et al. A meta-analysis of add-on use of spironolactone in patients with resistant hypertension[J].International journal of cardiology,2017,233:113-117.
     [34]Liu L, Xu B, Ju Y. Addition of spironolactone in patients with resistant hypertension: A meta-analysis of randomized controlled trials[J]. Clinical and Experimental Hypertension,2017,39(3):257-263.
     [35]Chen C, Zhu XY, Li D, et al. Clinical efficacy and safety of spironolactone in patients with resistant hypertension: A systematic review and meta-analysis[J].Medicine,2020,99(34):e21694.
     [36]Galceran I, Vázquez S, Durán X, et al. Renal safety outcomes of spironolactone in patients with resistant hypertension[J].Nefrología (English Edition),2020,40(4):413-419.
     [37]Ferreira J P, Rossignol P, Pizard A, et al. Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure[J].Heart,2019,105(4):307-314.
     [38]Rossignol P, Claggett BL, Liu J, et al. Spironolactone and resistant hypertension in heart failure with preserved ejection fraction[J].American journal of hypertension,2018,31(4):407-414.
     [39]Tsujimoto T, Kajio H. Spironolactone Use and Improved Outcomes in Patients With Heart Failure With Preserved Ejection Fraction With Resistant Hypertension[J].Journal of the American Heart Association,2020,9(23):e018827.
     [40]Djoumessi RN, Noubiap JJN, Kaze FF, et al. Effect of low-dose spironolactone on resistant hypertension in type 2 diabetes mellitus: a randomized controlled trial in a sub-Saharan African population[J].BMC research notes,2016,9(1):1-9.
     [41]Yang L, Zhang H, Cai M, et al. Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea[J].Clinical and Experimental Hypertension,2016,38(5):464-468.
     [42]Vaclavik J,Tavacova D,Kocianova E,et al. Adverseeffects of spirono-lactone during long-term treatment of resistant arterial hypertension[J].Journal of Hypertension,2017,35:e123.
     [43]Agarwal R, Rossignol P, Romero A, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial[J].The Lancet,2019,394(10208):1540-1550.
     [44]Rossignol P, Williams B, Mayo MR, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure[J]. European journal of heart failure,2020,22(8):1462-1471.
     [45]Williams B, MacDonald TM, Morant SV, et al. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies[J].The lancet Diabetes & endocrinology,2018,6(6):464-475.
     [46]Eguchi K, Kabutoya T, Hoshide S, et al. Add-on use of eplerenone is effective for lowering home and ambulatory blood pressure in drug‐resistant hypertension[J].The Journal of Clinical Hypertension,2016,18(12):1250-1257.
     [47]Kalizki T, Schmidt B MW, Raff U, et al. Low dose‐eplerenone treatment decreases aortic stiffness in patients with resistant hypertension[J].The Journal of Clinical Hypertension,2017,19(7):669-676.
     [48]Schneider A, Schwab J, Karg MV, et al. Low-dose eplerenone decreases left ventricular mass in treatment-resistant hypertension[J].Journal of Hypertension,2017,35(5):1086-1092.
     [49]Krasińska B, Miazga A, Cofta S, et al. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension[J].Polskie Archiwum Medycyny Wewnetrznej,2016,126(5):330-339.
     [50]Krasińska B, Cofta S, Szczepaniak-Chiche L, et al. The effects of epleren-one on the circadian blood pressure pattern and left ventricular hypertrophy in patients with obstructive sleep apnea and resistant hypertension—a randomized, controlled trial[J].Journal of clinical medicine,2019,8(10):1671.
     [51]Eschalier R, McMurray JJV, Swedberg K, et al. Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure)[J]. Journal of the American College of Cardiology,2013,62(17):1585-1593.
     [52]Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor[J]. Current Opinion in Nephrology and hypertension,2015,24(5):417-424.
     [53]Ruilope LM, Nowack C, Bakris GL. Masked and Nocturnal Hypertension in the ARTS-DN ABPM Sub-Study with Finerenone[J]. Journal of the American Society of Hypertension,2016,1(10):e7.
     [54]Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial[J].European Heart Journal,2013,34(31):2453-2463.
     [55]Filippatos G, Anker SD, Bhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease[J].European Heart Journal,2016,37(27):2105-2114.
     [56]Sato N, Ajioka M, Yamada T, et al. A randomized controlled study of finerenone vs. eplerenone in Japanese patients with worsening chronic heart failure and diabetes and/or chronic kidney disease[J].Circulation Journal,2016:CJ-16-0122.
     [57]Ito S, Itoh H, Rakugi H, et al. Double-blind randomized phase 3 study comparing esaxerenone (CS-3150) and eplerenone in patients with essential hypertension (ESAX-HTN study)[J]. Hypertension,2020,75(1):51-58.