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The Role of Direct Renin Inhibition in Clinical Practice

Focus on Combination Therapy

American Journal of Cardiovascular Drugs volume 11, pages 303–315 (2011)Cite this article

Abstract

Monotherapy with most antihypertensive agents reduces systolic BP by about 10 mmHg (‘Rule of 10’). Thus, the majority of hypertensive patients require combination therapy to achieve BP goals. In this review, we provide a brief overview of the renin-angiotensin-aldosterone system (RAAS) and discuss the rationale, clinical evidence, and shortcomings related to the use of angiotensin-converting enzyme (ACE) inhibitors in combination with angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We summarize the rationale and clinical evidence supporting the use of the direct renin inhibitor (DRI) aliskiren, particularly in combination with other antihypertensive classes, including in high-risk patients with diabetes mellitus and with or without diabetic nephropathy. DRIs may be useful in combination with ACE inhibitors or ARBs as they provide a more complete blockade of the RAAS, effectively suppressing residual angiotensin II production and the counter-regulatory increase in plasma renin activity observed in patients receiving monotherapy with ACE inhibitors or ARBs.

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References

  1. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–13.

    PubMed  Article  Google Scholar 

  2. Ostchega Y, Yoon SS, Hughes J, et al. Hypertension awareness, treatment, and control — continued disparities in adults: United States, 2005–2006. NCHS data brief 2003 (No. 3). Hyattsville (MD): National Center for Health Statistics.

  3. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988–2008. JAMA 2010; 303: 2043–50.

    PubMed  Article  CAS  Google Scholar 

  4. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA 2002; 287: 1003–10.

    PubMed  Article  Google Scholar 

  5. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich) 2002; 4: 393–404.

    Article  Google Scholar 

  6. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Diuretic versus 6h-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 2003; 42: 239–46.

    Article  Google Scholar 

  7. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–86.

    PubMed  Article  CAS  Google Scholar 

  8. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003; 290: 2805–16.

    PubMed  Article  CAS  Google Scholar 

  9. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366: 895–906.

    PubMed  Article  Google Scholar 

  10. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008; 359: 2417–28.

    PubMed  Article  CAS  Google Scholar 

  11. Chobanian AV, Bakris GL, Black HR, 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.

    PubMed  Article  CAS  Google Scholar 

  12. Mancia G, De Backer G, Dominiczak A, et al. 2007 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). J Hypertens 2007; 25: 1105–87.

    PubMed  Article  CAS  Google Scholar 

  13. Cleophas TJ. Mechanisms offsetting the beneficial effects of antihypertensive drugs: a problem increasingly considered but incompletely understood. Am J Ther 1998; 5: 413–9.

    PubMed  Article  CAS  Google Scholar 

  14. Sanoski CA. Aliskiren: an oral direct renin inhibitor for the treatment of hypertension. Pharmacotherapy 2009; 29: 193–212.

    PubMed  Article  CAS  Google Scholar 

  15. Epstein BJ, Smith SM, Choksi R. Recent changes in the landscape of combination RAS blockade. Expert Rev Cardiovasc Ther 2009; 7: 1373–84.

    PubMed  Article  CAS  Google Scholar 

  16. Yoneda T, Takeda Y, Usukura M, et al. Aldosterone breakthrough during angiotensin II receptor blockade in hypertensive patients with diabetes mellitus. Am J Hypertens 2007; 20: 1329–33.

    PubMed  Article  CAS  Google Scholar 

  17. Milliez P, Girerd X, Plouin PF, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243–8.

    PubMed  Article  CAS  Google Scholar 

  18. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–75.

    PubMed  Article  CAS  Google Scholar 

  19. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362: 767–71.

    PubMed  Article  CAS  Google Scholar 

  20. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893–906.

    PubMed  Article  CAS  Google Scholar 

  21. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–59.

    PubMed  Article  CAS  Google Scholar 

  22. Mann JF, Schmieder RE, McQueen M, 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: 547–53.

    PubMed  Article  CAS  Google Scholar 

  23. Loriga G, Vidili G, Ruggenenti P, et al. Renal hemodynamics and renoprotection. Nephron Clin Pract 2008; 110: c213–9.

    PubMed  Article  CAS  Google Scholar 

  24. Freel EM, Tsorlalis IK, Lewsey JD, et al. Aldosterone status associated with insulin resistance in patients with heart failure: data from the ALOFT study. Heart 2009; 95: 1920–4.

    PubMed  Article  CAS  Google Scholar 

  25. Brunner HR, Laragh JH, Baer L, et al. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972; 286: 441–9.

    PubMed  Article  CAS  Google Scholar 

  26. Francis GS, Cohn JN, Johnson G, et al. Plasma norepinephrine, plasma renin activity, and congestive heart failure: relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation 1993; 87 (6 Suppl.): VI40–8.

    PubMed  CAS  Google Scholar 

  27. Latini R, Masson S, Anand I, et al. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT. Eur Heart J 2004; 25: 292–9.

    PubMed  Article  CAS  Google Scholar 

  28. Rouleau JL, Packer M, Moye L, et al. Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril. J Am Coll Cardiol 1994; 24: 583–91.

    PubMed  Article  CAS  Google Scholar 

  29. Sim JJ, Shi JM, Calara FB, et al. Plasma renin activity as a risk factor for cardiovascular and cerebrovascular disease. Presented at: 25th Annual Scientific Meeting and Exposition of the American Society of Hypertension; New York (NY); 2010 May 1–4.

  30. Nussberger J, Wuerzner G, Jensen C, et al. Angiotensin II suppression in humans by the orally active renin inhibitor aliskiren (SPP100): comparison with enalapril. Hypertension 2002; 39: E1–8.

    PubMed  Article  CAS  Google Scholar 

  31. Azizi M, Ménard J, Bissery A, et al. Hormonal and hemodynamic effects of aliskiren and valsartan and their combination in sodium-replete normotensive individuals. Clin J Am Soc Nephrol 2007; 2: 947–55.

    PubMed  Article  CAS  Google Scholar 

  32. Brown MJ. Aliskiren. Circulation 2008; 118: 773–84.

    PubMed  Article  CAS  Google Scholar 

  33. Holsworth DD, Powell NA, Downing DM, et al. Discovery of novel non-peptidic ketopiperazine-based renin inhibitors. Bioorg Med Chem 2005; 13: 2657–64.

    PubMed  Article  CAS  Google Scholar 

  34. Bezencon O, Bur D, Weller T, et al. Design and preparation of potent, non-peptidic, bioavailable renin inhibitors. J Med Chem 2009; 52: 3689–702.

    PubMed  Article  CAS  Google Scholar 

  35. Tice CM, Xu Z, Yuan J, et al. Design and optimization of renin inhibitors: orally bioavailable alkyl amines. Bioorg Med Chem Lett 2009; 19: 3541–5.

    PubMed  Article  CAS  Google Scholar 

  36. Stanton A, Jensen C, Nussberger J, et al. Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren. Hypertension 2003; 42: 1137–43.

    PubMed  Article  CAS  Google Scholar 

  37. Azizi M, Ménard J, Bissery A, et al. Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the angiotensin II-renin feedback interruption. J Am Soc Nephrol 2004; 15: 3126–33.

    PubMed  Article  Google Scholar 

  38. Drummond W, Munger MA, Rafique EM, et al. Antihypertensive efficacy of the oral direct renin inhibitor aliskiren as add-on therapy in patients not responding to amlodipine monotherapy. J Clin Hypertens (Greenwich) 2007; 9: 742–50.

    Article  CAS  Google Scholar 

  39. Jordan J, Engeli S, Boye SW, et al. Direct renin inhibition with aliskiren in obese patients with arterial hypertension. Hypertension 2007; 49: 1047–55.

    PubMed  Article  CAS  Google Scholar 

  40. Nussberger J, Gradman AH, Schmieder RE, et al. Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension. Int J Clin Pract 2007; 61: 1461–8.

    PubMed  Article  CAS  Google Scholar 

  41. O’Brien E, Barton J, Nussberger J, et al. Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker. Hypertension 2007; 49: 276–84.

    PubMed  Article  Google Scholar 

  42. Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007; 49: 1157–63.

    PubMed  Article  CAS  Google Scholar 

  43. Oparil S, Yarows SA, Patel S, et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007; 370: 221–9.

    PubMed  Article  CAS  Google Scholar 

  44. Seed A, Gardner R, McMurray J, et al. Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure. Eur J Heart Fail 2007; 9: 1120–7.

    PubMed  Article  CAS  Google Scholar 

  45. Uresin Y, Taylor AA, Kilo C, et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst 2007; 8: 190–8.

    PubMed  Article  CAS  Google Scholar 

  46. Villamil A, Chrysant SG, Calhoun D, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007; 25: 217–26.

    PubMed  Article  CAS  Google Scholar 

  47. Geiger H, Barranco E, Gorostidi M, et al. Combination therapy with various combinations of aliskiren, valsartan, and hydrochlorothiazide in hypertensive patients not adequately responsive to hydrochlorothiazide alone. J Clin Hypertens (Greenwich) 2009; 11: 324–32.

    Article  CAS  Google Scholar 

  48. Palatini P, Jung W, Shlyakhto E, et al. Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study. J Hum Hypertens 2010; 24: 93–103.

    PubMed  Article  CAS  Google Scholar 

  49. Andersen K, Weinberger MH, Constance CC, et al. Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during longterm (6 months) treatment and withdrawal in patients with hypertension. J Renin Angiotensin Aldosterone Syst 2009; 10: 157–67.

    PubMed  Article  CAS  Google Scholar 

  50. Stanton AV, Gradman AH, Schmieder RE, et al. Aliskiren monotherapy does not cause paradoxical blood pressure rises: meta-analysis of data from 8 clinical trials. Hypertension 2010; 55: 54–60.

    PubMed  Article  CAS  Google Scholar 

  51. Yarows SA. Aliskiren/valsartan combination for the treatment of cardiovascular and renal diseases. Expert Rev Cardiovasc Ther 2010; 8: 19–33.

    PubMed  Article  CAS  Google Scholar 

  52. Mende CW. Application of direct renin inhibition to chronic kidney disease. Cardiovasc Drugs Ther 2010; 24: 139–49.

    PubMed  Article  CAS  Google Scholar 

  53. McMurray JJ, Pitt B, Latini R, et al. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail 2008; 1: 17–24.

    PubMed  Article  CAS  Google Scholar 

  54. Verma A, Juszczynka K, Uno H, et al. Neurohumoral effects of a new oral direct renin inhibitor in patients with left ventricular hypertrophy (ALLAY) trial [abstract 7B.4]. J Hypertens 2009; 27 Suppl. 4: S314.

    Google Scholar 

  55. Illingworth DR. Management of hypercholesterolemia. Med Clin North Am 2000; 84: 23–42.

    PubMed  Article  CAS  Google Scholar 

  56. Bays H, Dujovne C. Colesevelam HCl: a non-systemic lipid-altering drug. Expert Opin Pharmacother 2003; 4: 779–90.

    PubMed  Google Scholar 

  57. Gradman AH, Schmieder RE, Lins RL, et al. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005; 111:1012–8.

    PubMed  Article  CAS  Google Scholar 

  58. Musini VM, Fortin PM, Bassett K, et al. Blood pressure lowering efficacy of renin inhibitors for primary hypertension. Cochrane Database Syst Rev 2008; Issue 4. Art No.: CD007066. DOI: 10.1002/14651858.CD007066.pub2:.

  59. Schmieder RE, Philipp T, Guerediaga J, et al. Long-term antihypertensive efficacy and safety of the oral direct renin inhibitor aliskiren: a 12-month randomized, double-blind comparator trial with hydrochlorothiazide. Circulation 2009; 119:417–25.

    PubMed  Article  CAS  Google Scholar 

  60. Schmieder RE, Philipp T, Guerediaga J, et al. Aliskiren-based therapy lowers blood pressure more effectively than hydrochlorothiazide-based therapy in obese patients with hypertension: sub-analysis of a 52-week, randomized, double-blind trial. J Hypertens 2009; 27: 1493–501.

    PubMed  Article  CAS  Google Scholar 

  61. Gradman AH, Weir MR, Wright M, et al. Efficacy, safety and tolerability of aliskiren, a direct renin inhibitor, in women with hypertension: a pooled analysis of eight studies. J Hum Hypertens 2010; 24: 721–9.

    PubMed  Article  CAS  Google Scholar 

  62. Pool JL, Schmieder RE, Azizi M, et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am J Hypertens 2007; 20: 11–20.

    PubMed  Article  CAS  Google Scholar 

  63. Yarows SA, Oparil S, Patel S, et al. Aliskiren and valsartan in stage 2 hypertension: subgroup analysis of a randomized, double-blind study. Adv Ther 2008; 25: 1288–302.

    PubMed  Article  CAS  Google Scholar 

  64. Duggan ST, Chwieduk CM, Curran MP. Aliskiren: a review of its use as monotherapy and as combination therapy in the management of hypertension. Drugs 2010; 70: 2011–49.

    PubMed  Article  CAS  Google Scholar 

  65. Whaley-Connell A, Purkayastha D, Yadao A, et al. Central pressure and biomarker responses to renin inhibition with hydrochlorothiazide and ramipril in obese hypertensives: the ATTAIN study. Cardiorenal Med 2011; 1: 53–66.

    PubMed  Article  CAS  Google Scholar 

  66. Ferdinand KC, Pool J, Weitzman R, et al. Peripheral and central blood pressure responses of combination aliskiren/hydrochlorothiazide and amlodipine monotherapy in African American patients with stage 2 hypertension: the ATLAAST trial. J Clin Hypertens 2011; Epub 18 Jan 2011.

  67. Brown MJ, McInnes GT, Papst CC, et al. Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial. Lancet 2011; 377: 312–20.

    PubMed  Article  CAS  Google Scholar 

  68. Duprez DA, Munger MA, Botha J, et al. Aliskiren for geriatric lowering of systolic hypertension: a randomized controlled trial. J Hum Hypertens 2009; 24: 600–8.

    PubMed  Article  Google Scholar 

  69. Basile J, Babazadeh S, Lillestol M, et al. Comparison of aliskiren/ hydrochlorothiazide combination therapy with hydrochlorothiazide monotherapy in older patients with stage 2 systolic hypertension: results of the ACTION study. J Clin Hypertens 2011; Epub 2011 Jan 25.

  70. White WB, Bresalier R, Kaplan AP, et al. Safety and tolerability of the direct renin inhibitor aliskiren: a pooled analysis of clinical experience in more than 12,000 patients with hypertension. J Clin Hypertens (Greenwich) 2010; 12: 765–75.

    Article  CAS  Google Scholar 

  71. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9.

    PubMed  Article  CAS  Google Scholar 

  72. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60.

    PubMed  Article  CAS  Google Scholar 

  73. Persson F, Rossing P, Reinhard H, et al. Renal effects of aliskiren compared to and in combination with irbesartan in patients with type 2 diabetes, hypertension and albuminuria. Diabetes Care 2009; 32: 1873–9.

    PubMed  Article  CAS  Google Scholar 

  74. Parving HH, Persson F, Lewis JB, et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008; 358: 2433–46.

    PubMed  Article  CAS  Google Scholar 

  75. Persson F, Lewis JB, Lewis EJ, et al. Aliskiren in combination with losartan reduces albuminuria independent of baseline blood pressure in patients with type 2 diabetes and nephropathy. Clin J Am Soc Nephrol 2011; 6: 1025–31.

    PubMed  Article  CAS  Google Scholar 

  76. Persson F, Lewis JB, Lewis EJ, et al. Impact of baseline renal function on the efficacy and safety of aliskiren added to losartan in patients with type 2 diabetes and nephropathy. Diabetes Care 2010; 33: 2304–9.

    PubMed  Article  Google Scholar 

  77. Persson F, Rossing P, Schjoedt KJ, et al. Time course of the antiproteinuric and antihypertensive effects of direct renin inhibition in type 2 diabetes. Kidney Int 2008; 73: 1419–25.

    PubMed  Article  CAS  Google Scholar 

  78. Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561–6.

    PubMed  Article  CAS  Google Scholar 

  79. Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am Heart J 2001; 141: 334–41.

    PubMed  Article  CAS  Google Scholar 

  80. de Simone G, Gottdiener JS, Chinali M, et al. Left ventricular mass predicts heart failure not related to previous myocardial infarction: the Cardiovascular Health Study. Eur Heart J 2008; 29: 741–7.

    PubMed  Article  Google Scholar 

  81. Solomon SD, Appelbaum E, Manning WJ, 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: 530–7.

    PubMed  Article  CAS  Google Scholar 

  82. Solomon SD, Shin SH, Shah A, et al. Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction. Eur Heart J 2011; 32: 1227–34.

    PubMed  Article  CAS  Google Scholar 

  83. Bakris GL, Kuritzky L. Monitoring and managing urinary albumin excretion: practical advice for primary care clinicians. Postgrad Med 2009; 121: 51–60.

    PubMed  Article  Google Scholar 

  84. Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27: 2121–58.

    PubMed  Article  CAS  Google Scholar 

  85. Parving HH, Brenner BM, McMurray JJ, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant 2009; 24: 1663–71.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

Editorial assistance was provided by Oxford PharmaGenesis Inc., and was funded by Novartis Pharmaceuticals Corporation. Drs Rashid and Mende had full control over the contents of the manuscript.

Dr Rashid has served on speakers bureaus for Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, and sanofi-aventis. Dr Mende has received honoraria as a member of speakers bureaus for Bristol-Myers Squibb, Forest Laboratories, Novartis, and sanofi-aventis, and has served on advisory board panels for Novartis.

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  1. Clinical Assistant Professor, Cardiology, Baylor College of Medicine, Texas Heart Institute, Kelsey Seybold Clinic, St Luke’s Episcopal Hospital, 6624 Fannin Street, OMT, 20th Floor, Houston, TX, 77030, USA

    Haroon-Ur Rashid

  2. Department of Nephrology, University of California at San Diego, La Jolla, CA, USA

    Christian Mende

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Rashid, HU., Mende, C. The Role of Direct Renin Inhibition in Clinical Practice. Am J Cardiovasc Drugs 11, 303–315 (2011). https://doi.org/10.2165/11594140-000000000-00000

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Keywords

  • Valsartan
  • Ramipril
  • Plasma Renin Activity
  • Aliskiren
  • HCTZ