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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

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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.

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Acknowledgments

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

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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

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  1. Luis Sargento
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  2. Andre Vicente Simões
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  4. Nuno Lousada
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Corresponding author

Correspondence to Luis Sargento.

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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.

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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)

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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

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