American Journal of Cardiology
Volume 105, Issue 6 , Pages 849-852 , 15 March 2010

Current Status of Dual Renin Angiotensin Aldosterone System Blockade for the Treatment of Cardiovascular Diseases

  • Steven G. Chrysant, MD, PhD

      Affiliations

    • Corresponding Author InformationCorresponding author: Tel: 405-721-6662; fax: 405-721-8417

Received 1 October 2009 ,Revised 5 November 2009 ,Accepted 5 November 2009.

References 

  1. Chrysant SG. Vascular remodeling: the role of angiotensin-converting enzyme inhibitors. Am Heart J. 1998;135:S21–S30
  2. Dzau V. The cardiovascular continuum and renin-angiotensin-aldosterone blockade. J Hypertens. 2005;23(suppl):S9–S17
  3. Vaughn EF. Renin, angiotensin and aldosterone system in the pathogenesis and management of hypertensive vascular disease. Am J Med. 1972;52:633–652
  4. Westermann D, Riad A, Lettau O, Roks A, Savvalis K, Becher PM, et al. Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure. Hypertension. 2008;52:1068–1075
  5. Thybo NK, Stephens N, Cooper A, Aakjaer C, Heagerty AM, Mulvaney MJ. Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension. 1995;25:474–481
  6. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, De Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint Reduction (LIFE) in hypertension: a randomized trial against atenolol. Lancet. 2002;359:995–1003
  7. Solomon SD, Appelbaum E, Manning WJ, Verma A, Berglund T, Lukashevich V, et al. Effect of the direct renin inhibitor aliskiren, the angiotensin receptor blocker losartan or both on left ventricular mass in patients with hypertension and left ventricular hypertrophy. Circulation. 2009;119:530–537
  8. Turnbull F, Neal B, Pfeffer M, Kostis J, Algert C, Woodward M, et al. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J Hypertens. 2007;25:951–958
  9. Menard J, Campbell DT, Azizi M, Gonzales MF. Synergistic effects of ACE inhibition and Ang II antagonism on blood pressure, cardiac weight, and renin in spontaneously hypertensive rats. Circulation. 1997;96:3072–3078
  10. Van Den Meiracker AH, Manintveld AJ, Admiraal PH, Ritsema Van Eck HJ, Boosma F, Derkx FH, et al. Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response?. J Hypertens. 1992;10:803–812
  11. Van De Wal RM, Plokker HW, Lok DJ, Boosma F, Vanderhorst FA, Van Veldhuisen DJ, et al. Determinants of increased angiotensin II levels in severe chronic heart failure patients despite ACE inhibition. Int J Cardiol. 2006;26:367–372
  12. Mooser V, Nussberger J, Juillerat L, Burnier M, Waeber B, Bildville J, et al. Reactive hyper-reninemia is a major determinant of plasma angiotensin II during ACE inhibition. J Cardiovasc Pharmacol. 1990;15:276–282
  13. Hollenberg NK, Fisher ND, Price DA. Pathways for angiotensin II generation in intact human tissue: evidence from comparative pharmacological interruption of the renin system. Hypertension. 1998;32:387–392
  14. Werner C, Baumhakel M, Teo KK, Schmieder R, Mann J, Unger T, et al. RAS blockade with ARB and ACE inhibitors: current perspective on rationale and patient selection. Clin Res Cardiol. 2008;97:418–431
  15. Azizi M, Guyene TT, Chatellier G, Wargon M, Menard J. Additive effects of losartan and enalapril on blood pressure and plasma active renin. Hypertension. 1997;29:634–640
  16. Chrysant SG, Chrysant GS. The pleiotropic effects of angiotensin receptor blockers. J Clin Hypertens. 2006;8:261–268
  17. Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the Candesartan and Lisinopril Microalbuminuria (CALM) study. Br J Med. 2000;21:1440–1414
  18. Izzo JL, Weinberg MS, Hainer JW, Kerkering J, Tou CK. Antihypertensive efficacy of candesartan-lisinopril in combination vs uptitration of lisinopril: the AMAZE trials. J Clin Hypertens. 2004;6:485–493
  19. Doulton TW, He FJ, Macgregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension. 2005;45:880–886
  20. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547–1559
  21. Pool JL, Schmieder RE, Azizi M, Aldigier JC, Januszewicz A, Zidek W, et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am J Hypertens. 2007;20:11–20
  22. Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007;370:221–229
  23. Chrysant SG, Murray AV, Hoppe UC, Dattani D, Patel S, Hsu H, et al. Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis. Curr Med Res Opin. 2008;24:1039–1047
  24. Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination of angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction. Arch Intern Med. 2007;167:1930–1936
  25. Lakhdar R, Al-Mallah MH, Lanfear DE. Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials. J Card Fail. 2008;14:181–188
  26. Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372:547–553
  27. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK AVOID Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008;358:2433–2446
  28. Forclaz A, Maillard M, Nussberger J, Brunner HR, Burnier M. Angiotensin II receptor blockade (Is there truly a benefit of adding an ACE inhibitor?). Hypertension. 2003;41:31–36
  29. Chrysant SG, Fagan T, Glazer R, Kriegman A. Effects of benazepril and hydrochlorothiazide, given alone and in low-and high-dose combinations, on blood pressure in patients with hypertension. Arch Fam Med. 1996;5:17–24
  30. Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH: a randomized double-blind, placebo-controlled, 8-week factorial efficacy and safety study. Clin Ther. 2008;30:587–604
  31. Villamil A, Chrysant SG, Calhoun D, Schober B, Hsu H, Matrisciano-Dimichino L, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens. 2007;25:217–226
  32. Messerli FH. The sudden demise of dual renin-angiotensin system blockade or the soft science of the surrogate endpoint. J Am Coll Cardiol. 2009;53:468–470
  33. Pfeffer MA, Sacks FM. Leapfrogging data: no shortcuts for safety or efficacy information. Circulation. 2008;118:2491–2494

PII: S0002-9149(09)02770-2

doi: 10.1016/j.amjcard.2009.11.044

American Journal of Cardiology
Volume 105, Issue 6 , Pages 849-852 , 15 March 2010