Skip to main content
SpringerLink
Log in

Compliance, Persistence, Healthcare Resource Use, and Treatment Costs Associated with Aliskiren plus ARB versus ACE Inhibitor plus ARB Combination Therapy

In US Patients with Hypertension

  • Original Research Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

Evidence is currently equivocal on the added benefits of dual blockade of the renin-angiotensin-aldosterone system with the combination of either an ACE inhibitor (ACEI) plus an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) or aliskiren, the first-in-class direct renin inhibitor, plus an ARB.

Objective

To compare the compliance, persistence, healthcare resource utilization, and healthcare costs associated with aliskiren plus ARB versus ACEI plus ARB combination therapies among adult patients diagnosed with hypertension.

Methods

Patients (aged ≥18 years) initiated on either combination therapy were identified in the Market-Scan Commercial and Medicare Supplemental Databases (1 July 2007 to 30 June 2008). The ARB components considered were candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan. The ACEI components included benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. Outcomes measured during the 6-month study period included the proportion of days covered (PDC), treatment discontinuation, healthcare resource utilization, and changes in healthcare costs (study period minus 6-month baseline values). Risk-adjusted differences in outcomes between treatments and associated 95% confidence intervals (CIs) were estimated using multivariate regression models, controlling for demographics, region, co-morbidities, prescription drug use, and resource utilization during the baseline period.

Results

Adjusting for baseline characteristics, aliskiren plus ARB patients (n= 1395) demonstrated a significantly higher PDC (67.0% vs 54.3%; difference 12.7%; 95% CI 10.6, 14.7) and a significantly lower discontinuation rate (50.4% vs 68.6%; odds ratio 0.46; 95% CI 0.40, 0.54) than ACEI plus ARB patients (n=16 507). Aliskiren plus ARB patients had significantly fewer all-cause hospitalizations (adjusted incidence rate ratio [IRR] 0.73; 95% CI 0.61,0.86) and significantly fewer all-cause emergency room (ER) visits (adjusted IRR 0.72; 95% CI 0.61, 0.85) than ACEI plus ARB patients. Compared with ACEI plus ARB therapy, aliskiren plus ARB therapy was associated with significantly larger increases in prescription costs by $US264 post therapy initiation (95% CI 153, 375), but with non-significantly greater reductions in total healthcare costs by -$583 (95% CI −2409, 1242) [2008 values].

Conclusion

In adult hypertensive patients, treatment with aliskiren plus ARB was associated with significantly better compliance/persistence and fewer hospitalizations and ER visits compared with ACEI plus ARB therapy. Reductions in total healthcare costs were non-significantly different between patients treated with aliskiren plus ARB versus ACEI plus ARB, despite the increased prescription costs associated with aliskiren plus ARB therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Chobanian AV, Bakris GL, Black HR, et al., and the National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. US Department of Health and Human Services, National Institute of Health [online]. Available from URL: http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf [Accessed 2010 Apr 15].

  2. Law MR, Wald NJ, Morris JK, et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326: 1427–31.

    Article  PubMed  CAS  Google Scholar 

  3. European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–53.

    Article  Google Scholar 

  4. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429–35.

    Article  Google Scholar 

  5. Pfeffer MA, Braunwald E, Moye LA, et al., the SAVE Investigators. 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.

    Article  PubMed  CAS  Google Scholar 

  6. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–75.

    Article  PubMed  CAS  Google Scholar 

  7. Bosch J, Lonn E, Pogue J, et al., HOPE/HOPE-TOO Study Investigators. Long-term effects of ramipril on cardiovascular events and on diabetes: results of the HOPE study extension. Circulation 2005; 112: 1339–46.

    Article  PubMed  Google Scholar 

  8. Lewis EJ, Hunsicker LG, Clarke WR, et al., Collaborative Study Group. 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.

    Article  PubMed  CAS  Google Scholar 

  9. Cohn JN. Reducing cardiovascular risk by blockade of the renin-agiotensin-aldosterone system. Adv Ther 2007; 24: 1290–304.

    Article  PubMed  CAS  Google Scholar 

  10. Azizi M, Linhart A, Alexander J, et al. Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients. J Hypertens 2000; 18: 1139–47.

    Article  PubMed  CAS  Google Scholar 

  11. Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 2005; 45: 880–6.

    Article  PubMed  CAS  Google Scholar 

  12. Unger T. Targeting cardiovascular protection: the concept of dual renin-angiotensin system control. Medscape J Med 2008; 10 Suppl.: S4.

    PubMed  Google Scholar 

  13. Bomback AS, Toto R. Dual blockade of the renin-angiotensin-aldosterone system: beyond the ACE inhibitor and angiotensin-II receptor blocker combination. Am J Hypertens 2009; 22: 1032–40.

    Article  PubMed  CAS  Google Scholar 

  14. Dusing R, Sellers F. ACE inhibitors, angiotensin receptor blockers and direct renin inhibitors in combination: a review of their role after the ONTARGET trial. Curr Med Res Opin 2009; 25: 2287–301.

    Article  PubMed  Google Scholar 

  15. Liebson PR, Amsterdam EA. Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET): implications for reduced cardiovascular risk. Prev Cardiol 2009; 12: 43–50.

    Article  PubMed  Google Scholar 

  16. Ong HT. Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers especially useful for cardiovascular protection? J Am Board Fam Med 2009; 22: 686–97.

    Article  PubMed  Google Scholar 

  17. Slagman MCJ, Navis G, Laverman GD. Dual blockade of the renin-angiotensin-aldosterone system in cardiac and renal disease. Curr Opin Nephrol Hypertens 2010; 19: 140–52.

    Article  PubMed  CAS  Google Scholar 

  18. The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–59.

    Article  Google Scholar 

  19. Mann JFE, Schmieder RE, McQueen M, et al., ONTARGET investigators. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Messerli FH. The sudden demise of dual renin-angiotensin system blockade or the soft science of the surrogate end point. J Am Coll Cardiol 2009; 53: 468–70.

    Article  PubMed  CAS  Google Scholar 

  22. Pimenta E, Oparil S. Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors. Ther Clin Risk Manag 2009; 5: 459–64.

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Andersen K, Weinberger MH, Egan B, et al. Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial. J Hypertens 2008; 26: 589–99.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  28. MarketScan Research Databases [online]. Available from URL: http://thom sonreuters.com/products_services/healthcare/healthcare_products/Pharma ceuticals/mktscan_res_db [Accessed 2010 Nov 5].

  29. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992: 45; 613–9.

    Article  PubMed  CAS  Google Scholar 

  30. Green PJ. Penalized likelihood for general semi-parametric regression models. Int Stat Rev 1987; 55: 245–59.

    Article  Google Scholar 

  31. Ruppert D, Wand MP, Carroll RJ. Semiparametric regression. New York: CUP, 2003.

    Book  Google Scholar 

  32. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Funding for this research was provided by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Joanne Chang, Weiyi Yang, Kristijan H. Kahler, Thomas Fellers, and John Orloff are employees of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Arielle G. Bensimon, Andrew P. Yu, Chun-Po Steve Fan, and Eric Q. Wu are employees of Analysis Group, Inc., Boston, MA, USA, which received funding for this study.

We would like to thank Amy Rudolph, PhD, Ricardo A. Rocha, MD, Craig Plauschinat, PharmD, Marjorie Gatlin, MD, Kim A. Heithoff, ScD, Jean Lian, PhD, and Chris Zacker, PhD, for their critical review of the manuscript.

Author information

Authors and Affiliations

  1. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

    Joanne Chang, Weiyi Yang, Kristijan H. Kahler, Thomas Fellers & John Orloff

  2. Analysis Group, Inc., 111 Huntington Ave, 10th Floor, Boston, Massachusetts, 02199, USA

    Arielle G. Bensimon, Andrew P. Yu, Chun-Po Steve Fan &  Eric Q. Wu PhD

Authors
  1. Joanne Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiyi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristijan H. Kahler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Fellers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John Orloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arielle G. Bensimon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andrew P. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chun-Po Steve Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eric Q. Wu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric Q. Wu PhD.

Appendix 1

Appendix 1

Unadjusted comparisons of 6-month healthcare outcomes among patients with hypertension who received aliskiren plus angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) vs ACE inhibitor (ACEI) plus ARB therapy.

figure U1figure U1

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, J., Yang, W., Kahler, K.H. et al. Compliance, Persistence, Healthcare Resource Use, and Treatment Costs Associated with Aliskiren plus ARB versus ACE Inhibitor plus ARB Combination Therapy. Am J Cardiovasc Drugs 11, 21–32 (2011). https://doi.org/10.2165/11586570-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11586570-000000000-00000

Keywords

Search

Navigation