Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension

Journal of Human Hypertension volume 21, pages 780–787 (2007)Cite this article

Abstract

Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension (mean sitting diastolic blood pressure (msDBP)⩾105 mm Hg and <120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20 mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was required. Aliskiren-based treatment (ALI) was similar to lisinopril-based treatment (LIS) with respect to the proportion of patients reporting an adverse event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%; LIS 3.4%). The most frequently reported AEs in both groups were headache, nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions from baseline to LIS in msDBP (ALI −18.5 mm Hg vs LIS −20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) −1.0, 4.4)) and mean sitting systolic blood pressure (ALI −20.0 mm Hg vs LIS −22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI −1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or reduction from baseline⩾10 mm Hg) were 81.5% with ALI and 87.9% with LIS. Approximately half of patients required the addition of HCTZ to achieve BP control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone, or in combination with HCTZ, in patients with severe hypertension.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R . 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: 1903–1913.

    Article  Google Scholar 

  2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252.

    Article  CAS  Google Scholar 

  3. European Society of Hypertension–European Society of Cardiology. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053.

  4. Bloom BS . Continuation of initial antihypertensive medication after 1 year of therapy. Clin Ther 1998; 20: 671–681.

    Article  CAS  Google Scholar 

  5. Burke TA, Sturkenboom MC, Lu SE, Wentworth CE, Lin Y, Rhoads GG . Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice. J Hypertens 2006; 24: 1193–1200.

    Article  Google Scholar 

  6. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M 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.

    Article  Google Scholar 

  7. Sica DA . Calcium channel blocker-related periperal edema: can it be resolved? J Clin Hypertens (Greenwich) 2003; 5: 291–294, 297.

    Article  Google Scholar 

  8. Israili ZH, Hall WD . Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 1992; 117: 234–242.

    Article  CAS  Google Scholar 

  9. Dicpinigaitis PV . Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest 2006; 129: 169S–173S.

    Article  CAS  Google Scholar 

  10. Azizi M, Menard J, Bissery A, Guyenne TT, Bura-Riviere A, Vaidyanathan S 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: 3126–3133.

    Article  Google Scholar 

  11. Skeggs Jr LT, Kahn JR, Lentz K, Shumway NP . The preparation, purification, and amino acid sequence of a polypeptide renin substrate. J Exp Med 1957; 106: 439–453.

    Article  CAS  Google Scholar 

  12. Wood JM, Maibaum J, Rahuel J, Grutter MG, Cohen NC, Rasetti V et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun 2003; 308: 698–705.

    Article  CAS  Google Scholar 

  13. Nussberger J, Wuerzner G, Jensen C, Brunner HR . Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension 2002; 39: E1–E8.

    Article  CAS  Google Scholar 

  14. Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP . Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005; 111: 1012–1018.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Villamil A, Chrysant S, 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.

    Article  CAS  Google Scholar 

  17. Sica D, Gradman AH, Lederballe O, Meyers M, Cai J, Keefe D . Aliskiren, a novel renin inhibitor, is well tolerated and has sustained BP-lowering effects alone or in combination with HCTZ during long-term (52 weeks) treatment of hypertension. Eur Heart J 2006; 27 (Suppl): 121.

    Google Scholar 

  18. Gossmann J, Thurmann P, Bachmann T, Weller S, Kachel HG, Schoeppe W et al. Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. Kidney Int 1996; 50: 973–978.

    Article  CAS  Google Scholar 

  19. Rell K, Koziak K, Jarzyo I, Lao M, Gaciong Z . Correction of posttransplant erythrocytosis with enalapril. Transplantation 1994; 57: 1059–1063.

    Article  CAS  Google Scholar 

  20. Midtvedt K, Hartmann A, Holdaas H, Fauchald P . Efficacy of nifedipine or lisinopril in the treatment of hypertension after renal transplantation: a double-blind randomised comparative trial. Clin Transplant 2001; 15: 426–431.

    Article  CAS  Google Scholar 

  21. Radevski I, Skudicky D, Candy G, Sathekge S, Strugo V, Sareli P . Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension. Am J Hypertens 1999; 12: 194–203.

    Article  CAS  Google Scholar 

  22. Oparil S, Aurup P, Snavely D, Goldberg A . Efficacy and safety of losartan/hydrochlorothiazide in patients with severe hypertension. Am J Cardiol 2001; 87: 721–726.

    Article  CAS  Google Scholar 

  23. Oparil S, Levine JH, Zuschke CA, Gradman AH, Ripley E, Jones DW et al. Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators. Am J Cardiol 1999; 84: 289–293.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by Novartis Pharma AG.

Author information

Authors and Affiliations

  1. Technical University Dresden, Heart Center, University Hospital, Dresden, Germany

    R H Strasser

  2. Department of Internal Medicine, La Paz Hospital, Madrid, Spain

    J G Puig

  3. 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary

    C Farsang

  4. Novartis Pharma AG, Basel, Switzerland

    M Croket & H van Ingen

  5. Novartis Institutes for Biomedical Research, Cambridge, MA, USA

    J Li

Authors
  1. R H Strasser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J G Puig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Farsang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Croket
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H van Ingen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R H Strasser.

Additional information

Trial registry: This trial is registered at ClinicalTrials.gov with trial identifier NCT00219050.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Strasser, R., Puig, J., Farsang, C. et al. A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension. J Hum Hypertens 21, 780–787 (2007). https://doi.org/10.1038/sj.jhh.1002220

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1002220

Keywords

This article is cited by

Search

Advanced search

Quick links