Outcomes of Different Antihypertensive Regimens

  • Takeshi Fujiwara
  • Kazuomi KarioEmail author


In this review, we introduce the main results of nine historical and landmark clinical trials, TOMHS, INSIGHT, LIFE, ALLHAT, ANBP2, CONVINCE, VALUE, ASCOT-CAFE, and ACCOMPLISH, that had a major impact on current guidelines for the management of hypertension. The most important objectives in the management of hypertension are to reduce BP levels significantly in the early phase and to reach the BP goals without fail, especially in high-risk patients with hypertensive complications. We must make every effort to confer the benefits of antihypertensive therapy to hypertensive patients, in order to reduce their cardiovascular outcomes and extend their healthy life spans.


Blood pressure Lifestyles improvement Diuretic β-blocker ACE inhibitor CCB ARB Central aortic pressure 


  1. 1.
    Williams B, Williams H, Northedge J, Crimmins J, Caulfield M, Watts M, et al. Hypertension: the clinical management of primary hypertension in adults, Update of clinical guidelines 18 and 34. NICE clinical guideline no. 127. London: Published by the National Clinical Guideline Centre at the Royal College of Physicians; 2011. Scholar
  2. 2.
    Mancia G, Fagard R, Narkiewixz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.CrossRefGoogle Scholar
  3. 3.
    James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20.CrossRefGoogle Scholar
  4. 4.
    Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16:14–26.CrossRefGoogle Scholar
  5. 5.
    Shimamoto K, Ando K, Fujita T, Hasebe N, Higaki J, Horiuchi M, et al. The Japanese Society of Hypertension guidelines for the management of hypertension (JSH2014). Hypertens Res. 2014;37:253–392.CrossRefGoogle Scholar
  6. 6.
    Daskalopoulou SS, Rabi DM, Zarnke KB, Dasgupta K, Nerenberg K, Cloutier L, et al. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2015;31:549–68.CrossRefGoogle Scholar
  7. 7.
    Neaton JD, Grimm RH Jr, Prineas RJ, Stamler J, Grandits GA, Elmer PJ, et al. For the Treatment of Mild Hypertension Study Research Group. Treatment of Mild Hypertension Study. Final results. Treatment of Mild Hypertension Study Research Group. JAMA. 1993;270:713–24.CrossRefGoogle Scholar
  8. 8.
    Brown MJ, Palmer CR, Castaigne A, de Leeuw PW, Mancia G, Rosenthal T, Ruilope LM. Morbidity and mortality in patients randomized to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GIFT study: Interventional as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000;356:366–72.CrossRefGoogle Scholar
  9. 9.
    Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, LIFE Study Group, et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359:995–1003.CrossRefGoogle Scholar
  10. 10.
    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981–97.CrossRefGoogle Scholar
  11. 11.
    SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255–64.CrossRefGoogle Scholar
  12. 12.
    Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350:757–64.CrossRefGoogle Scholar
  13. 13.
    Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Second Australian National Blood Pressure Study Group, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583–92.CrossRefGoogle Scholar
  14. 14.
    Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, CONVINCE Research Group, et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289:2073–82.CrossRefGoogle Scholar
  15. 15.
    Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, VALUE trial group, et al. Outcome in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomized trial. Lancet. 2004;363:2022–31.CrossRefGoogle Scholar
  16. 16.
    Brunner HR. Experimental and clinical evidence that angiotensin II is an independent risk factor for cardiovascular disease. Am J Cardiol. 2001;87:3C–9C.CrossRefGoogle Scholar
  17. 17.
    Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113:1213–25.CrossRefGoogle Scholar
  18. 18.
    Safar ME, Blacher J, Pannier B, Guerin AP, Marchais SJ, Guyonvarc'h PM, London GM. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39:735–8.CrossRefGoogle Scholar
  19. 19.
    Kingwell BA, Waddell TK, Medley TL, Cameron JD, Dart AM. Large artery stiffness predicts ischemic threshold in patients with coronary artery disease. J Am Coll Cardiol. 2002;40:773–9.CrossRefGoogle Scholar
  20. 20.
    Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ. Vasoactive drugs influence aortic augmentation index independently of pulse-wave velocity in health men. Hypertension. 2001;37:1429–33.CrossRefGoogle Scholar
  21. 21.
    Hirata K, Vlachopoulos C, Adji A, O'Rourke MF. Benefits from angiotensin-converting enzyme inhibitor ‘beyond blood pressure lowering’: beyond blood pressure or beyond the brachial artery? J Hypertens. 2005;23:551–7.CrossRefGoogle Scholar
  22. 22.
    Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Rationale, design, methods and baseline demography of perticipants of the Anglo-Scandinavian Cardiac Outcomes Trial. J Hypertens. 2001;19:1139–47.CrossRefGoogle Scholar
  23. 23.
    Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359:2417–28.CrossRefGoogle Scholar
  24. 24.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee, 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.CrossRefGoogle Scholar
  25. 25.
    Zhang X, Hintze TH. Amlodipine releases nitric oxide from canine coronary microvessels: an unexpected mechanism of action of a calcium channel-blocking agent. Circulation. 1998;97:576–80.CrossRefGoogle Scholar
  26. 26.
    Neutel JM, Smith DH, Weber MA. Effect of antihypertensive monotherapy and combination therapy on arterial distensibility and left ventricular mass. Am J Hypertens. 2004;17:37–42.CrossRefGoogle Scholar
  27. 27.
    Jamerson KA, Bakris GL, Wun CC, Dahlöf B, Lefkowitz M, Manfreda S, et al. Rationale and design of the avoiding cardiovascular events through combination therapy in patients living with systolic hypertension (ACCOMPLISH) trial: the first randomized controlled trial to compare the clinical outcome effects of first-line combination therapies in hypertension. Am J Hypertens. 2004;17:793–801.PubMedGoogle Scholar
  28. 28.
    Matsui Y, Eguchi K, O’Rourke MF, Ishikawa J, Miyashita H, Shimada K, Kario K. Differential effects between a calcium channel blocker and a diuretic when used in combination with angiotensin II receptor blocker on central aortic pressure in hypertensive patients. Hypertension. 2009;54:716–23.CrossRefGoogle Scholar
  29. 29.
    Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236–41.CrossRefGoogle Scholar
  30. 30.
    Kario K, Tomitani N, Kanegae H, Ishii H, Uchiyama K, Yamagiwa K, et al. Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring – The NOCTURNE Study. Circ J. 2017;81:948–57.CrossRefGoogle Scholar
  31. 31.
    Chobanian AV. The hypertension paradox - more uncontrolled disease despite improved therapy. N Engl J Med. 2009;361:878–87.CrossRefGoogle Scholar
  32. 32.
    Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Cardiovascular Medicine, Department of MedicineJichi Medical University School of MedicineShimotsukeJapan
  2. 2.Higashiagatsuma-machi National Health Insurance ClinicGunmaJapan
  3. 3.Division of Cardiovascular Medicine, Department of MedicineJichi Medical University School of MedicineTochigiJapan

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