Advertisement

Approaches for the Management of Resistant Hypertension in 2020

  • Wilbert S. AronowEmail author
Resistant Hypertension (L Drager, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Resistant Hypertension

Abstract

Purpose of Review

Resistant hypertension is diagnosed if the blood pressure (BP) is not controlled despite optimum doses of 3 first-line classes of antihypertensive drugs including a thiazide diuretic or if adequate BP control needs 4 or more antihypertensive drugs from different classes.

Recent Findings

Pseudohypertension and white coat hypertension must be excluded. Poor patient compliance, inadequate doses of antihypertensive drugs, poor office BP measurement technique, and having to pay for costs of drugs are factors associated with pseudoresistant hypertension. Secondary hypertension must be excluded and treated. Therapy of resistant hypertension includes improving compliance with use of medication, detection, and treatment of secondary hypertension, use of lifestyle measures, and treatment of obesity and other comorbidities. Switching the patient from hydrochlorothiazide to a longer acting thiazide-type diuretic such as chlorthalidone may improve BP control. The beneficial effects of thiazide diuretics are reduced when the glomerular filtration rate is reduced to less than 40 mL/min/1.73 m2. These patients should be treated with a loop diuretic such as furosemide every 12 h. If a fourth antihypertensive drug is needed to control blood pressure in persons treated with adequate doses of antihypertensive drugs from different classes including a thiazide-type diuretic, a mineralocorticoid receptor antagonist should be added to the therapeutic regimen. Further research is needed on investigational drugs and device therapy for treating resistant hypertension.

Summary

Clinical trials are indicated for the treatment of resistant hypertension by sacubitril/valsartan and also by firibastat.

Keywords

Resistant hypertension Antihypertensive drugs Diuretics Mineralocorticoid receptor antagonists Lifestyle measures Device therapy for hypertension 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Aronow has no conflicts of interest to disclose. This author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or drugs or devices discussed in this manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Coillins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH ASPC/NMA/PCNA guideline for the prevention, detection, evaluation and management of high blood pressure in adults. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127–248 These guidelines discuss the management of resistant hypertension.PubMedGoogle Scholar
  2. 2.
    Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011;305:913–22.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Czernichow S, Zanchetti A, Turnbull F, Barzi F, Ninomiya KAP, et al. The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline blood pressure: meta-analysis of randomized trials. J Hypertens. 2011;29:4–16.PubMedGoogle Scholar
  4. 4.
    Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB Sr, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935–59.PubMedGoogle Scholar
  5. 5.
    Blood Pressure-Lowering Treatment Trialists’ Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014;384:591–8.Google Scholar
  6. 6.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 Report. JAMA. 2003;289:2560–72.PubMedGoogle Scholar
  7. 7.
    Chiong JR, Aronow WS, Khan IA, Nair CK, Vijayaraghavan K, Dart RA, et al. Secondary hypertension : current diagnosis and treatment. Int J Cardiol. 2008;124:6–21.PubMedGoogle Scholar
  8. 8.
    Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.PubMedGoogle Scholar
  9. 9.
    Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years. A randomized clinical trial. JAMA. 2016;315:2673–82.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Bundy JD, Li C, Stuchlik P, Bu X, Kelly TN, Mills KT, et al. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiol. 2017;2:775–81.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Oparil S, Lewis CE. Should patients with cardiovascular risk factors receive intensive treatment of hypertension to <120/80 mm target? A protagonist view from the SPRINT trial (Systolic Blood Pressure Intervention trial). Circulation. 2016;134:1308–10.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Aronow WS. Managing hypertension in the elderly: what is different, what is the same? Curr Hypertens Rep. 2017;19:67.  https://doi.org/10.1007/s11906-017-0764-8.CrossRefPubMedGoogle Scholar
  13. 13.
    Rochlani Y, Khan MH, Aronow WS. Managing hypertension in patients aged 75 years and older. Curr Hypertens Rep. 2017;19:88.  https://doi.org/10.1007/s11906-017-0785-3.CrossRefPubMedGoogle Scholar
  14. 14.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 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. Developed in collaboration with the American Academy of Family Physicians, the American College of Chest Physicians, and International Society for Heart and Lung Transplantation. J Am Coll Cardiol. 2017;70:776–803.PubMedGoogle Scholar
  15. 15.
    Upadhyay A, Earley A, Haynes SM, Uhlig K. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154:541–8.PubMedGoogle Scholar
  16. 16.
    SPS3 Study Group, Benavente OR, Coffey CS, Conwit R, Hart RG, McClure LA, et al. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet 2013; 382: 507–515.Google Scholar
  17. 17.
    Oparil S. SPS3 evidence supports intensive blood pressure control. Circulation. 2016;133:552–4.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2015;313:603–15.PubMedGoogle Scholar
  19. 19.
    Margolis KL, O'Connor PJ, Morgan TM, Buse JB, Cohen RM, Cushman WC, et al. Outcomes of combined cardiovascular risk factor management strategies in type 3 diabetes: the ACCORD randomized trial. Diabetes Care. 2014;37:1721–8.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Soliman EZ, Byington RP, Bigger JT, Evans G, Okin PM, Goff DC Jr, et al. Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with diabetes mellitus: Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial. Hypertension. 2015;66:1123–9.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Aronow WS. Orthostatic hypotension in diabetics in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial. Hypertension. 2016;68:851–2.PubMedGoogle Scholar
  22. 22.
    Wang WT, You LK, Chiang CE, Sung SH, Chuang SY, Cheng HM, et al. Comparative effectiveness of blood pressure-lowering drugs in patients who have already suffered from stroke: traditional and Bayesian network meta-analysis of randomized trials. Medicine. 2016;95:e3302.PubMedPubMedCentralGoogle Scholar
  23. 23.
    •• Aronow WS. Lifestyle measures for treating hypertension. Arch Med Sci. 2017;13:1241–3 This paper discusses lifestyle measures for treating hypertension. PubMedPubMedCentralGoogle Scholar
  24. 24.
    Ojji DB, Mayosi B, Francis V, Badri M, Cornelius V, Smythe W, et al. Comparison of drug therapies for lowering blood pressure in black Africans. N Engl J Med. 2019;380:2429–39.PubMedGoogle Scholar
  25. 25.
    •• Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57:2037–114 These guidelines discuss management of resistant hypertension. PubMedGoogle Scholar
  26. 26.
    Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, et al. AHA/ACC/ASH scientific statement. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol. 2015;65:1998–2038.PubMedGoogle Scholar
  27. 27.
    Law MR, Morris JK, Wald NJ. Use of BP lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.  https://doi.org/10.1136/bmj.b1665.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Aronow WS. Current role of beta blockers in the treatment of hypertension. Expert Opin Pharmacother. 2010;11:2599–607.PubMedGoogle Scholar
  29. 29.
    The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385–90.Google Scholar
  30. 30.
    Freemantle N, Cleland J, Young P, Mason J, Harrison J. Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318:1730–7.PubMedPubMedCentralGoogle Scholar
  31. 31.
    HOPE (Heart Outcomes Prevention Evaluation) Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145–53.Google Scholar
  32. 32.
    The European trial on reduction of cardiac events with perindopril in stable coronary artery disease investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782–8.Google Scholar
  33. 33.
    Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial. N Engl J Med. 1992;327:669–77.PubMedGoogle Scholar
  34. 34.
    Leon MB, Rosing DR, Bonow RO, Lipson LC, Epstein SE. Clinical efficacy of verapamil alone and combined with propranolol in treating patients with chronic stable angina pectoris. Am J Cardiol. 1981;48:131–9.PubMedGoogle Scholar
  35. 35.
    Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease:2011 update. A guideline from the American Heart Association and American College of Cardiology Foundation. Endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol. 2011;58:2432–46.PubMedGoogle Scholar
  36. 36.
    Pitt B, White H, Nicolau J, Martinez F, Gheorghiade M, Aschermann M, et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol. 2005;46:425–31.PubMedGoogle Scholar
  37. 37.
    Elkayam U, Amin J, Mehra A, Vasquez J, Weber L, Rahimtoola SH. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation. 1990;82:1954–61.PubMedGoogle Scholar
  38. 38.
    Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation. 1991;83:52–60.PubMedGoogle Scholar
  39. 39.
    Aronow WS, Ahn C, Kronzon I. Effect of propranolol versus no propranolol on total mortality plus nonfatal myocardial infarction in older patients with prior myocardial infarction, congestive heart failure, and left ventricular ejection fraction > or = 40% treated with diuretics plus angiotensin-converting enzyme inhibitors. Am J Cardiol. 1997;80:207–9.PubMedGoogle Scholar
  40. 40.
    Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015;131:34–42.PubMedGoogle Scholar
  41. 41.
    Appel LJ, Wright JT Jr, Greene T, Agodoa LY, Astor BC, Bakris GL, et al. Intensive blood pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010;363:918–29.PubMedPubMedCentralGoogle Scholar
  42. 42.
    PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033–41.Google Scholar
  43. 43.
    Bavry AA, Anderson RD, Gong Y, Denardo SJ, Cooper-Dehoff RM, Handberg EM, et al. Outcomes among hypertensive patients with concomitant peripheral and coronary artery disease: findings from the INternational VErapamil-SR/Trandolapril STudy. Hypertension. 2010;55:48–53.PubMedGoogle Scholar
  44. 44.
    Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J, et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med. 2005;165:1410–9.PubMedGoogle Scholar
  45. 45.
    Palmer SC, Mavridis D, Navarese E, Craig JC, Tonelli M, Salanti G, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet. 2015;385:2047–56.PubMedGoogle Scholar
  46. 46.
    Black HR, Davis B, Barzilay J, Nwachuku C, Baimbridge C, Marginean H, et al. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Diabetes Care. 2008;32:353–60.Google Scholar
  47. 47.
    Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr, et al. ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. J Am Coll Cardiol. 2010;55:e27–12.PubMedGoogle Scholar
  48. 48.
    Tsai TT, Nienaber CA, Eagle KA. Acute aortic syndromes. Circulation. 2005;112:3802–13.PubMedGoogle Scholar
  49. 49.
    •• Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–26 This American Heart Association 2008 scientific statement discusses the diagnosis, evaluation, and treatment of resistant hypertension. PubMedGoogle Scholar
  50. 50.
    Tataru AP, Barry AR. A systematic review of add-on pharmacologic therapy in the treatment of resistant hypertension. Am J Cardiovasc Drugs. 2017;17:311–8.PubMedGoogle Scholar
  51. 51.
    Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ. 2012;345:e7473.PubMedGoogle Scholar
  52. 52.
    Gandelman G, Aronow WS, Varma R. Prevalence of adequate blood pressure control in self pay or Medicare patients versus Medicaid or private insurance patients with systemic hypertension followed in a university cardiology or general medicine clinic. Am J Cardiol. 2004;94:815–6.PubMedGoogle Scholar
  53. 53.
    Vongpatanasin W. Resistant hypertension. A review of diagnosis and management. JAMA. 2014;311:2216–24.PubMedGoogle Scholar
  54. 54.
    Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125:1635–42.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Kumbhani DJ, Steg PG, Cannon CP, Eagle KA, Smith SC Jr, Crowley K, et al. Resistant hypertension: a frequent and ominous finding among hypertensive patients with atherothrombosis. Eur Heart J 2013; 34: 1204–1214.PubMedGoogle Scholar
  56. 56.
    Bangalore S, Davis BR, Cushman WC, Pressel SL, Muntner PM, Calhoun DA, et al. Treatment-resistant hyprtension and outcomes based on randomized treatment groups in ALLHAT. Am J Med. 2017;130:439–48.PubMedGoogle Scholar
  57. 57.
    •• Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P. Prevalence of apparent treatment-resistant hypertension in the United States. Comparison of the 2008 and 2018 American Heart Association Scientific Statements on resistant hypertension. Hypertension. 2019;73:424–31 The 2018 American Heart Association scientific statement reports that the prevalence of treatment-resistant hypertension in the United States is 9.7%, that 3.2% of those with resistant hypertension are taking chlorthalidone or indapamide, and that 9.0% of those with resistant hypertension are taking spironolactone or eplerenone. PubMedPubMedCentralGoogle Scholar
  58. 58.
    Petry NM, Rash CJ, Byrne S, Ashraf S, White WB. Financial reinforcers for improving medication adherence: findings from a meta-analysis. Am J Med. 2012;125:888–96.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Burnier M, Wuerzner G, Struijker-Boudier H, Urquhart J. Measuring, analyzing, and managing drug adherence in resistant hypertension. Hypertension. 2013;62:218–25.PubMedGoogle Scholar
  60. 60.
    Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock SJ, Wines RC, et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012;157:785–95.PubMedGoogle Scholar
  61. 61.
    Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008;16:CD000011.Google Scholar
  62. 62.
    Ceral J, Habrdova V, Vorisek V, Bima M, Pelouch R, Solar M. Difficult-to-control arterial hypertension or uncooperative patients? The assessment of serum antihypertensive drug levels to differentiate non-responsiveness from non-adherence to recommended therapy. Hypertens Res. 2011;34:87–90.PubMedGoogle Scholar
  63. 63.
    Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013;31:766–74.PubMedGoogle Scholar
  64. 64.
    •• Durand H, Hayes P, Morrissey EC, Newell J, Casey M, Murphy AW, et al. Medication adherence among patients with apparent treatment-resistant hypertension: systematic review and meta-analysis. J Hypertens. 2017;35:2346–57 An analysis of 24 studies showed that the prevalence of nonadherence to drug therapy is 31.2% in patients with resistant hypertension. PubMedGoogle Scholar
  65. 65.
    Durand H, Hayes P, Hasrhen B, Conneely A, Finn DP, Casey M, et al. Medication adherence for resistant hypertension: assessing theoretical predictors of adherence using direct and indirect adherence measures. Br J Health Psychol. 2018;23:949–66.PubMedGoogle Scholar
  66. 66.
    •• Adams M, Bellone JM, Wright BM, Rutecki GW. Evaluation and pharmacologic approach to patients with resistant hypertension. Postgrad Med. 2012;124:74–82 This paper discusses the evaluation and drug treatment of resistant hypertension.PubMedGoogle Scholar
  67. 67.
    Hwang AY, Dietrich E, Pepine CJ, Smith SM. Resistant hypertension: mechanisms and treatment. Curr Hypertens Rep. 2017;56.  https://doi.org/10.1007/s11906-017-0754-x.
  68. 68.
    Ernst ME, Carter BL, Geordt CJ, Steffensmeier JJ, Phillips BB, Zimmerman MB, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertens. 2006;47:352–8.Google Scholar
  69. 69.
    Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52:1749–57.PubMedPubMedCentralGoogle Scholar
  70. 70.
    •• Oparil S, Schmieder RE. New approaches in the treatment of hypertension. Circ Res. 2015;116:1074–95 This paper discusses new approaches to the treatment of resistant hypertension.PubMedGoogle Scholar
  71. 71.
    Kalizki T, Schmidt BMW, Raff U, Reinold A, Schwarz TK, Schneider MP, et al. Low dose-eplerenone treatment decreases aortic stiffness in patients with resistant hypertension. J Clin Hypertens. 2017;19:669–76.Google Scholar
  72. 72.
    •• Chapman N, Dobson J, Wilson S, Dahlof B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49:839–45 This study supports the use of spironolactone in patients with resistant hypertension.PubMedGoogle Scholar
  73. 73.
    Egan BM, Li J. Role of aldosterone blockade in resistant hypertension. Semin Nephrol. 2014;34:273–84.PubMedGoogle Scholar
  74. 74.
    Williams B, MacDonald TM, Moran S, Webb DJ, Sever P, McInnes G, 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. Lancet. 2015;386:2059–68.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Williams B, MacDonald TM, Moran S, Webb DJ, Sever P, McInnes GT, et al. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. Lancet Diabetes Endocrinol. 2018;6:464.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Makai P, IntHout J, Deinum J, Jenniskens K, GJV W. A network meta-analysis of clinical management strategies for treatment-resistant hypertension: making optimal use of the evidence. J Gen Intern Med. 2017;32:921–30.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Krieger EM, Drager LF, Giorgi DMA, Pereira AC, Barreto-Filho JAS, Nogueira AR, et al. Spironolactone versus clonidine as a fourth-drug therapy for resistant hypertension. The ReHOT randomized study (Resistant Hypertension Optimal Treatment). Hypertens. 2018;71:681–90.Google Scholar
  78. 78.
    •• Smith SM, Gurka MJ, Calhoun DA, Gong Y, Pepine CJ, RM C-DH. Optimal systolic blood pressure target in resistant and non-resistant hypertension: a pooled analysis of patient-level data from SPRINT and ACCORD. Am J Med. 2018;131:1463–72 This study supports a systolic blood pressure goal of less than 120 mmHg to reduce cardiovascular events and all-cause mortality in patients with resistant hypertension. PubMedPubMedCentralGoogle Scholar
  79. 79.
    Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension. Lancet. 2012;380:593–600.Google Scholar
  80. 80.
    Burnier M. Update on endothelin receptor antagonists in hypertension. Curr Hypertens Rep. 2018;51.  https://doi.org/10.1007/s11906-018-0848-0.
  81. 81.
    Dhaun N, Webb DJ. Endothelins in cardiovascular biology and therapeutics. Nat Rev Cardiol. 2019;16:491–502.PubMedGoogle Scholar
  82. 82.
    Williams B, Cockcroft JR, Kario K, Zappe DH, Brunel PC, Wang Q, et al. Effects of sacubitril/valsartan versus olmesartan on central hemodynamics in the elderly with systolic hypertension: the PARAMETER study. Hypertens. 2017;69:411–20.Google Scholar
  83. 83.
    Malik AH, Aronow WS. Efficacy of sacubitril/valsartan in hypertension. Am J Ther. 2019; In press.  https://doi.org/10.1097/MJT.0000000000000925.
  84. 84.
    Kario K. The sacubitril/valsartan, a first-in-class, angiotensin receptor neprilysin inhibitor (ARNI): potential uses in hypertension, heart failure, and beyond. Curr Cardiol Rep. 2018;20:1–8.  https://doi.org/10.1007/s11886-018-0944-4.CrossRefGoogle Scholar
  85. 85.
    Ferdinand KC, Balavoine F, Besse B, Black HR, Desbrandes S, Dittrich HC, et al. Efficacy and safety of firibastat, a first-in-class brain aminopeptidae A inhibitor, in hypertensive overweight patients of multiple ethnic origins. A phase2, open-label, multicenter, dose-titrating study. Circulation. 2019;140:138–46.Google Scholar
  86. 86.
    Bhatt DL, Kandzari DE, O'Neill WW, D’Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–401.Google Scholar
  87. 87.
    Bakris GL, Townsend RR, Liu M, Cohen SA, D’Agostino R, Flack JM, et al. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. J Am Coll Cardiol. 2014;64:1071–8.PubMedGoogle Scholar
  88. 88.
    Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomized, sham-controlled, proof-of-concept trial. Lancet. 2017;390:2160–70.PubMedGoogle Scholar
  89. 89.
    Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HT-ON MED proof-of-concept randomized trial. Lancet. 2018;391:2346–55.PubMedGoogle Scholar
  90. 90.
    Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicenter, international, single-blind, randomized, sham-controlled trial. Lancet. 2018;391:2335–45.PubMedGoogle Scholar
  91. 91.
    Sardar P, Bhatt DL, Kirtane AJ, Kennedy KF, Chatterjee S, Giri J, et al. Sham-controlled randomized trials of catheter-based renal denervation in patients with hypertension. J Am Coll Cardiol. 2019;73:1633–42.PubMedGoogle Scholar
  92. 92.
    Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56:1254–8.PubMedGoogle Scholar
  93. 93.
    Lobo MD, Sobatka PA, Stanton A, Cockcroft JR, Sulke N, Dolan E, et al. Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial. Lancet. 2015;385:3634–41.Google Scholar
  94. 94.
    •• Rosa J, Widimsky P, Waldauf P, Lambert L, Zelinka T, Taborsky M, et al. Role of adding spironolactone and renal denervation in true resistant hypertension: one-year outcomes of randomized PRAGUE-15 study. Hypertens. 2016;67:397–403 This study showed that addition of spironolactone was more effective than renal artery denervation in reducing systolic blood pressure in patients with resistant hypertension. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of CardiologyWestchester Medical Center and New York Medical CollegeValhallaUSA
  2. 2.Department of MedicineWestchester Medical Center and New York Medical CollegeValhallaUSA

Personalised recommendations