Skip to main content

Advertisement

SpringerLink
Log in

Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community

  • Original Articles
  • Published:
Journal of General Internal Medicine Aims and scope Submit manuscript

Abstract

OBJECTIVE: To evaluate the dose-related benefit of angiotensin-converting enzyme (ACE) inhibitor therapy among older adults with heart failure and to evaluate whether low-dose ACE inhibitor therapy is better than none.

DESIGN: Observational cohort study.

SETTING: Community-dwelling older adults in Ontario, Canada.

PATIENTS/PARTICIPANTS: We identified 16,539 adults 66 years or older who survived 45 days following their first heart failure hospitalization discharge.

MEASUREMENT AND MAIN RESULTS: Multivariate techniques including propensity scores were used to study the association between the dose of ACE inhibitor therapy dispensed and 3 outcomes: survival, survival or heart failure rehospitalization, and survival or all-cause hospitalization at 1 year of follow-up. Logistic regression models explored the association between initial dose dispensed and subsequent dose reduction or drug cess-ation. Overall, 10,793 (65.3%) of patients were dispensed ACE inhibitor therapy, with more than a third (3,935; 36.5%) initiated on low-dose therapy. Relative to dispensing of low-dose ACE inhibitor therapy, nonuse was associated with increased mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.02 to 1.22). Dispensing medium-dose therapy provided a benefit similar to low-dose (HR, 0.94; CI, 0.86 to 1.03) and dispensing of high-dose therapy was associated with improved survival benefit (HR, 0.76; CI, 0.68 to 0.85). Relative to dispensing of low-dose ACE inhibitor therapy, dispensing high-dose conferred a benefit (HR, 0.87; CI, 0.80 to 0.95) on the composite outcome of 1-year mortality or heart failure hospitalization and the composite outcome of 1-year mortality or all-cause hospitalization (HR, 0.87; CI, 0.81 to 0.93). Relative to those dispensed low-dose ACE inhibitor therapy, those initially dispensed high-dose therapy were twice as likely to have their subsequent dose reduced or the therapy discontinued (odds ratio, 2.36; CI, 2.07 to 2.69).

CONCLUSION: Our findings suggest that when possible, older adults should be titrated to the higher doses of ACE inhibitor therapy evaluated in clinical trials. If older adults cannot tolerate higher doses, then low-dose ACE inhibitor therapy is superior to none. High-dose ACE inhibitor therapy is not as well tolerated as lower doses.

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.

Similar content being viewed by others

References

  1. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure); 2001. American College of Cardiology Website. Available at: http://www.acc.org/clinical/guidelines/failure/hf_index.htm. Accessed November 24, 2003.

  2. American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Guidelines for the evaluation and management of heart failure. J Am Coll Cardiol. 1995;26:1376–98.

    Article  Google Scholar 

  3. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293–302.

    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;316:1429–34.

    Article  Google Scholar 

  5. Captopril-Digoxin Multicenter Research Group. Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA. 1988;259:539–44.

    Article  Google Scholar 

  6. Advisory Council to Improve Outcomes Nationwide in Heart Failure. Consensus recommendations for the management of heart failure. Am J Cardiol. 1999;83(2A):1A-38A.

    Google Scholar 

  7. Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-coverting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999;100:2312–8.

    PubMed  CAS  Google Scholar 

  8. Nanas JN, Alexopoulos G, Anastasiou-Nana MI, et al. Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. J Am Coll Cardiol. 2000;36:2090–5.

    Article  PubMed  CAS  Google Scholar 

  9. Network Investigators. Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. Eur Heart J. 1998;19:481–9.

    Article  CAS  Google Scholar 

  10. Clement DL, De Buyzere M, Tomas M, Vanavermaete G, on behalf of the CHIPS investigators. Long-term effects of clinical outcome with low and high dose in the Captopril in Heart Insufficient Patients Study (CHIPS). Acta Cardiol. 1999;55:1–7.

    Article  Google Scholar 

  11. Krumholz HM, Wang Y, Parent EM, Mocalis J, Petrillo M, Radford MJ. Quality of care for elderly patients hospitalized with heart failure. Arch Intern Med. 1997;157:2242–7.

    Article  PubMed  CAS  Google Scholar 

  12. Forman DE, Chander RB, Lapane KL, Shah P, Stoukides J. Evaluating the use of angiotensin-converting enzyme inhibitors for older nursing home residents with chronic heart failure. J Am Geriatr Soc. 1998;46:1550–4.

    PubMed  CAS  Google Scholar 

  13. Chin MH, Wang JC, Zhang JZ, Lang RM. Utilization and dosing of angiotensin-converting enyme inhibitors for heart failure: effect of physician specialty and patient characteristics. J Gen Intern Med. 1997;12:563–6.

    Article  PubMed  CAS  Google Scholar 

  14. Alter DA, Naylor CD, Austin P, Tu JV. Effects of socioeconomic status on access to invasive cardiac procedures and on mortality after acute myocardial infarction. N Engl J Med. 1999;341:1359–67.

    Article  PubMed  CAS  Google Scholar 

  15. Rochon PA, Anderson GM, Tu JV, et al. Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose. J Am Geriatr Soc. 1999;47:954–9.

    PubMed  CAS  Google Scholar 

  16. Rochon PA, Anderson GM, Tu JV, et al. Use of beta-blocker therapy in the elderly following acute myocardial infarction. Can Med Assoc J. 1999;161:1403–8.

    CAS  Google Scholar 

  17. Naylor CD, Slaughter P. Cardiovascular Health and Services in Ontario. Toronto, Ontario: Institute for Clinical Evaluative Sciences (ICES); 1999.

    Google Scholar 

  18. Tu JV, Pashos CL, Naylor CD, et al. Use of cardiac procedures and outcomes in elderly patients with myocardial infarction in the United States and Canada. N Engl J Med. 1997;336:1500–5.

    Article  PubMed  CAS  Google Scholar 

  19. Tu J, Hannan EL, Anderson GM, et al. The fall and rise of carotid endarterectomy in the United States and Canada. N Engl J Med. 1998;339:1441–7.

    Article  PubMed  CAS  Google Scholar 

  20. Rochon PA, Tu JV, Anderson GM, et al. Rate of heart failure and 1-year survival for older people receiving low-dose beta-blocker therapy after myocardial infarction. Lancet. 2000;356:639–44.

    Article  PubMed  CAS  Google Scholar 

  21. Quan H, Parsons GA, Ghali WA. Validity of information on comorbidity derived from ICD-9-CCM administrative data. Med Care. 2002;40:675–85.

    Article  PubMed  Google Scholar 

  22. Barron HV, Viskin S, Lundstrom RJ, et al. Beta-blocker dosages and mortality after myocardial infarction: data from a large health maintenance organization. Arch Intern Med. 1998;158:449–53.

    Article  PubMed  CAS  Google Scholar 

  23. Konstam M, Dracup K, Baker D. Heart failure: evaluation and care of patients with left-ventricular systolic cysfunction. Rockville, Md: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services; 1994.

    Google Scholar 

  24. Canadian Pharmacists Association. Compendium of pharmaceuticals and specialities. 33rd ed. Ottawa, Ontario: Canadian Pharmacists Association; 1998.

    Google Scholar 

  25. Rochon PA, Fortin PR, Dear KBG, Minaker KL, Chalmers TC. Reporting of age data in clinical trials of arthritis: deficiencies and solutions. Arch Intern Med. 1993;153:243–8.

    Article  PubMed  CAS  Google Scholar 

  26. Charlson ME, Pompei PA, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

    Article  PubMed  CAS  Google Scholar 

  27. 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 

  28. Hosmer DW, Lemeshow S. Applied Survival Analysis. New York, NY: John Wiley and Sons; 1999.

    Google Scholar 

  29. Argesti A. Categorical Data Analysis. New York, NY: John Wiley and Sons; 1990.

    Google Scholar 

  30. Rubin D. Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127(8S):757–63.

    PubMed  CAS  Google Scholar 

  31. Uretsky BF, Shaver JA, Liang C et al. Modulation of hemodynamic effects with a converting enzyme inhibitor, lisinopril, with observations on long-term clinical, functional, and biochemical responses. Am Heart J. 1988;116:480–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Toronto, Canada

    Paula A. Rochon MD, MPH & Sudeep Gill MD

  2. Department of Health Policy, Management, and Evaluation, University of Toronto, Canada

    Paula A. Rochon MD, MPH, Susan E. Bronskill PhD, Muhammad Mamdani PharmD, MA, MPH, Geoffrey M. Anderson MD, PhD & Jack V. Tu MD, MSc, PhD

  3. Faculty of Pharmacy, University of Toronto, Canada

    Muhammad Mamdani PharmD, MA, MPH

  4. Institute for Clinical Evaluative Sciences, Sunnnybrook and Womens College Health Science Centre, Toronto, Ontario, Canada

    Paula A. Rochon MD, MPH, Kathy Sykora MSc, Susan E. Bronskill PhD, Muhammad Mamdani PharmD, MA, MPH, Geoffrey M. Anderson MD, PhD, Jack V. Tu MD, MSc, PhD & Andreas Laupacis MD

  5. Department of Medicine, Sunnnybrook and Womens College Health Science Centre, Toronto, Ontario, Canada

    Jack V. Tu MD, MSc, PhD & Andreas Laupacis MD

  6. Meyers Primary Care Institute, Fallon Healthcare System and University of Massachusetts Medical School, Worcester, Mass

    Jerry H. Gurwitz MD

  7. Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, 3560 Bathurst Street, M6A 2E1, Toronto, Ontario, Canada

    Paula A. Rochon MD, MPH & Sudeep Gill MD

Authors
  1. Paula A. Rochon MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathy Sykora MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susan E. Bronskill PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhammad Mamdani PharmD, MA, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Geoffrey M. Anderson MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jerry H. Gurwitz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sudeep Gill MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jack V. Tu MD, MSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andreas Laupacis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paula A. Rochon MD, MPH.

Additional information

Dr. Rochon was supported by an Investigator Award, Drs. Mamdani and Bronskill by New Investigator Awards, Dr. Gill by a Post-doctoral Award, Dr. Tu by a Canada Research Chair in Health Services Research, and Dr. Laupacis by a Senior Investigator Award, all from the Canadian Institutes for Health Research (CIHR).

This work was supported by the CIHR Chronic Disease New Emerging Team program (NET—54010) and the Physicians Services of Ontario. The NET program receives joint sponsorship from the Canadian Diabetes Association, the Kidney Foundation of Canada, the Heart and Stroke Foundation of Canada, and the CIHR Institutes of Nutrition, Metabolism, and Diabetes, and Circulatory and Respiratory Health.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rochon, P.A., Sykora, K., Bronskill, S.E. et al. Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community. J GEN INTERN MED 19, 676–683 (2004). https://doi.org/10.1111/j.1525-1497.2004.30328.x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1111/j.1525-1497.2004.30328.x

Key words

Search

Navigation