Skip to main content
SpringerLink
Log in

Treatment with Optimal Dose Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Has a Positive Effect on Long-Term Survival in Older Individuals (Aged >70 Years) and Octogenarians with Systolic Heart Failure

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background

Heart failure with reduced ejection fraction (HFrEF) is a disease of older people, but the target doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are unknown.

Objective

To evaluate the association of ACEI/ARB dose level with long-term survival in stable older patients (aged >70 years) and octogenarian outpatients with HFrEF.

Population and Methods

A total of 138 outpatients aged >70 years (35.5 % > 80 years), with an LVEF <40 % and who were clinically stable on optimal therapy were followed up for 3 years. The ACEI/ARB doses were categorized as: none (0), low (1–50 % target dose), and high (50–100 % target dose). The Cox regression survival model was adjusted for age, ischemic etiology, and renal function.

Results

ACEIs/ARBs were prescribed to 91.3 % of patients, and 52.9 % received the high dose. Survival improved with increasing ACEI/ARB dose level in the total population (Hazard Ratio [HR] = 0.67; 95 % confidence interval [CI] 0.55–0.82; p < 0.001), older patients aged >70 years (HR = 0.65; 95 % CI 0.51–0.83; p < 0.001), and octogenarians (HR = 0.71; 95 % CI 0.51–0.99; p = 0.045). The low (HR = 0.35; 95 % CI 0.16–0.76; p = 0.008) and high doses (HR = 0.13; 95 % CI 0.06–0.32; p < 0.001) improved survival compared with not receiving ACEIs/ARBs. The high dose was associated with a better survival than the low dose in the total population (HR = 0.35; 95 % CI 0.19–0.67; p = 0.001) and in a propensity score-matched cohort (HR = 0.41; 95 % CI 0.16–1.02; p = 0.056). In octogenarians, all dose levels were associated with improved survival compared with not receiving ACEIs/ARBs, but there was no difference between ACEI/ARB doses.

Conclusion

The achieved optimal dose of ACEIs/ARBs in ambulatory older people with HFrEF is associated with long-term survival.

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

Fig. 1

Similar content being viewed by others

References

  1. Miani D, Fresco C, Lucci D, et al. Italian Survey on Acute Heart Failure Investigators. Clinical characteristics, management, and prognosis of octogenarians with acute heart failure admitted to cardiology wards: results from the Italian Survey on Acute Heart Failure. Am Heart J. 2009;158:126–32.

    Article  PubMed  Google Scholar 

  2. Havranek EP, Masoudi FA, Westfall KA, et al. Spectrum of heart failure in older patients: results from the National Heart Failure Project. Am Heart J. 2002;143:412–7.

    Article  PubMed  Google Scholar 

  3. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. New Engl J Med. 2006;355:251–9.

    Article  CAS  PubMed  Google Scholar 

  4. Cowie MR, Wood DA, Coats AJ, et al. Incidence and aetiology of heart failure; a population-based study. Eur Heart J. 1999;20:421–8.

    Article  CAS  PubMed  Google Scholar 

  5. Zachariah D, Taylor J, Rowell N, et al. Drug therapy for heart failure in older patients: what do they want? J Geriatr Cardiol. 2015;12:165–73.

    PubMed  PubMed Central  Google Scholar 

  6. McMurray JJ, Adamopoulos S, Anker SD, ESC Committee for Practice Guidelines, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69.

    Article  CAS  PubMed  Google Scholar 

  7. Barywani SB, Ergatoudes C, Schaufelberger M, et al. Does the target dose of neurohormonal blockade matter for outcome in systolic heart failure in octogenarians? Int J Cardiol. 2015;187:666–72.

    Article  PubMed  Google Scholar 

  8. Heywood JT, Fonarow GC, Yancy CW, et al. Comparison of medical therapy dosing in outpatients cared for in cardiology practices with heart failure and reduced ejection fraction with and without device therapy: report from IMPROVE HF. Circ Heart Fail. 2010;3:596–605.

    Article  PubMed  Google Scholar 

  9. Heywood JT, Fonarow GC, Yancy CW, et al. Influence of renal function on the use of guideline-recommended therapies for patients with heart failure. Am J Cardiol. 2010;105:1140–6.

    Article  PubMed  Google Scholar 

  10. Maggioni AP, Dahlström U, Filippatos G, et al. The heart failure pilot survey (ESCHF Pilot). Eur J Heart Fail. 2010;12:1076–84.

    Article  PubMed  Google Scholar 

  11. Gheorghiade M, Albert NM, Curtis AB, et al. Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. Congest Heart Fail. 2012;18:9–17.

    Article  CAS  PubMed  Google Scholar 

  12. Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106:2194–9.

    Article  PubMed  Google Scholar 

  13. Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26:215–25.

    Article  CAS  PubMed  Google Scholar 

  14. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–16.

    Article  CAS  PubMed  Google Scholar 

  15. Svensson M, Gustafsson F, Galatius S, et al. How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure? J Card Fail. 2004;10:297–303.

    Article  CAS  PubMed  Google Scholar 

  16. Verbrugge FH, Dupont M, De Vusser P, et al. Response to cardiac resynchronization therapy in elderly patients (≥70 years) and octogenarians. Eur J Heart Fail. 2013;15:203–10.

    Article  PubMed  Google Scholar 

  17. Metra M, Dei Cas L, Massie BM. Treatment of heart failure in the elderly: never say it’s too late. Eur Heart J. 2009;30:391–3.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Konstam MA, Neaton JD, Dickstein K, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomized, double-blind trial. Lancet. 2009;374:1840–8.

    Article  CAS  PubMed  Google Scholar 

  20. Witt CT, Kronborg MB, Nohr EA, et al. Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival. Eur Heart J Cardiovasc Pharmacother. 2015;1:182–8.

    Article  PubMed  Google Scholar 

  21. Steinberg BA, Cannon CP, Hernandez AF, et al. Medical therapies and invasive treatments for coronary artery disease by body mass: the “obesity paradox” in the Get With The Guidelines database. Am J Cardiol. 2007;100:1331–5.

    Article  PubMed  Google Scholar 

  22. Cullington D, Goode KM, Clark AL, Cleland JG. Heart rate achieved or betablocker dose in patients with chronic heart failure: which is the better target? Eur J Heart Fail. 2012;14:737–47.

    Article  CAS  PubMed  Google Scholar 

  23. Masoudi FA, Havranek EP, Wolfe P, et al. Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Am Heart J. 2003;146:250–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are thankful to Miss Ana Paula Pinto for administrative support.

Author information

Authors and Affiliations

  1. Heart Failure Unit, Cardiology Department, Pulido Valente Hospital, Lisbon North Hospital Centre, Alameda Linhas de Torres, 1769-001, Lisboa, Portugal

    Luis Sargento, Susana Longo, Nuno Lousada & Roberto Palma dos Reis

  2. Department of Internal Medicine, Pulido Valente Hospital, Lisbon North Hospital Centre, Lisbon, Portugal

    Andre Vicente Simões

Authors
  1. Luis Sargento
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Vicente Simões
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susana Longo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nuno Lousada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto Palma dos Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luis Sargento.

Ethics declarations

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Luis Sargento, André Vicente Simões, Susana Longo, and Roberto Palma dos Reis declare that they have no conflicts of interest that might be relevant to the contents of the manuscript.

Ethical approval

All studies included in this pooled analysis were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the studies.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 30 kb)

40266_2016_393_MOESM2_ESM.jpg

(A) The 3-year death rate according to the ACEI/ARB dose levels, in all cohorts and according to the age subgroups. (B) Adjusted survival curve in all populations according to the ACEI/ARB dose level (0, <50 % TD, 50–99 % TD, and TD). ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, CI confidence interval, HR hazard ratio, TD target dose (JPEG 157 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sargento, L., Simões, A.V., Longo, S. et al. Treatment with Optimal Dose Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Has a Positive Effect on Long-Term Survival in Older Individuals (Aged >70 Years) and Octogenarians with Systolic Heart Failure. Drugs Aging 33, 675–683 (2016). https://doi.org/10.1007/s40266-016-0393-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-016-0393-y

Keywords

Search

Navigation