American Journal of Cardiovascular Drugs

, Volume 11, Issue 1, pp 21–32

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
  • Joanne Chang
  • Weiyi Yang
  • Kristijan H. Kahler
  • Thomas Fellers
  • John Orloff
  • Arielle G. Bensimon
  • Andrew P. Yu
  • Chun-Po Steve Fan
  • Eric Q. Wu
Original Research Article

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.

References

  1. 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].Google Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Cohn JN. Reducing cardiovascular risk by blockade of the renin-agiotensin-aldosterone system. Adv Ther 2007; 24: 1290–304.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 12.
    Unger T. Targeting cardiovascular protection: the concept of dual renin-angiotensin system control. Medscape J Med 2008; 10 Suppl.: S4.PubMedGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–59.CrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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].Google Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 30.
    Green PJ. Penalized likelihood for general semi-parametric regression models. Int Stat Rev 1987; 55: 245–59.CrossRefGoogle Scholar
  31. 31.
    Ruppert D, Wand MP, Carroll RJ. Semiparametric regression. New York: CUP, 2003.CrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Joanne Chang
    • 1
  • Weiyi Yang
    • 1
  • Kristijan H. Kahler
    • 1
  • Thomas Fellers
    • 1
  • John Orloff
    • 1
  • Arielle G. Bensimon
    • 2
  • Andrew P. Yu
    • 2
  • Chun-Po Steve Fan
    • 2
  • Eric Q. Wu
    • 2
  1. 1.Novartis Pharmaceuticals CorporationEast HanoverUSA
  2. 2.Analysis Group, Inc.BostonUSA

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