Skip to main content
SpringerLink
Log in

Safety and Prognostic Impact of Early Treatment with Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients with Acute Heart Failure

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

Abstract

Background

Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been recommended for patients with heart failure, their clinical and prognostic impact in the very acute phase of acute heart failure (AHF) is unclear, mainly because data on their safety and efficacy are lacking.

Methods

This study was a post hoc analysis of the REALITY-AHF trial. Patients with AHF who did not take an ACEI or ARB at admission were enrolled. Patients who received these medications within 48 h of admission were categorized as the ACEI/ARB group, and all other patients were categorized as the no ACEI/ARB group. The primary endpoint was a composite of all-cause death and heart failure readmission within 1 year of admission.

Results

Of the 1682 patients in the REALITY-AHF cohort, 900 were enrolled in this study, and 288 (32%) were included in the ACEI/ARB group. After propensity score matching, 152 pairs were evaluated, and no significant difference was found for in-hospital mortality, worsening renal function, or length of hospital stay. The ACEI/ARB group had significantly higher event-free survival (hazard ratio 0.51; 95% confidence interval 0.32–0.82; p = 0.006).

Conclusions

Early initiation of ACEIs/ARBs within 48 h of admission for hospitalized patients with AHF was not associated with adverse events and correlated with improved outcomes at 1 year from admission.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. 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 

  2. SOLVD Investigators, Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. 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 

  3. Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992;327:669–77.

    Article  CAS  Google Scholar 

  4. Gheorghiade M, Hall V, Lakier JB, Goldstein S. Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure. J Am Coll Cardiol. 1989;13:134–42.

    Article  CAS  Google Scholar 

  5. Annane D, Bellissant E, Pussard E, Asmar R, Lacombe F, Lanata E, et al. Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema. Circulation. 1996;94:1316–24.

    Article  CAS  Google Scholar 

  6. Sigurdsson A, Swedberg K. Left ventricular remodelling, neurohormonal activation and early treatment with enalapril (CONSENSUS II) following myocardial infarction. Eur Heart J. 1994;15(Suppl B):14–9 (discussion 26–30).

    Article  Google Scholar 

  7. Latini R, Tognoni G, Maggioni AP, Baigent C, Braunwald E, Chen ZM, et al. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting. J Am Coll Cardiol. 2000;35:1801–7.

    Article  CAS  Google Scholar 

  8. Matsue Y, Damman K, Voors AA, Kagiyama N, Yamaguchi T, Kuroda S, et al. Time-to-furosemide treatment and mortality in patients hospitalized with acute heart failure. J Am Coll Cardiol. 2017;69:3042–51.

    Article  Google Scholar 

  9. Kondo T, Okumura T, Matsue Y, Shiraishi A, Kagiyama N, Yamaguchi T, et al. Specialty-related differences in the acute-phase treatment and prognosis in patients with acute heart failure—insights from REALITY-AHF. Circ J. 2018;83:174–81.

    Article  Google Scholar 

  10. Kuroda S, Damman K, Ter Maaten JM, Voors AA, Okumura T, Kida K, et al. Very early diuretic response after admission for acute heart failure. J Card Fail. 2019;25:12–9.

    Article  Google Scholar 

  11. Yamaguchi T, Kitai T, Miyamoto T, Kagiyama N, Okumura T, Kida K, et al. Effect of optimizing guideline-directed medical therapy before discharge on mortality and heart failure readmission in patients hospitalized with heart failure with reduced ejection fraction. Am J Cardiol. 2018;121:969–74.

    Article  Google Scholar 

  12. Kagiyama N, Kitai T, Hayashida A, Yamaguchi T, Okumura T, Kida K, et al. Prognostic value of BNP reduction during hospitalization in patients with acute heart failure. J Card Fail. 2019;1:1. https://doi.org/10.1016/j.cardfail.2019.04.004.

    Article  Google Scholar 

  13. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88:107–15.

    Article  CAS  Google Scholar 

  14. Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials. Circulation. 2015;132:302–61.

    Article  Google Scholar 

  15. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  CAS  Google Scholar 

  16. Metra M, Nodari S, Parrinello G, Bordonali T, Bugatti S, Danesi R, et al. Worsening renal function in patients hospitalised for acute heart failure: clinical implications and prognostic significance. Eur J Heart Fail. 2008;10:188–95.

    Article  Google Scholar 

  17. Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011;10:150–61.

    Article  Google Scholar 

  18. Haukoos JS, Lewis RJ. The propensity score. JAMA. 2015;314:1637.

    Article  CAS  Google Scholar 

  19. SOLVD Investigators, Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327:685–91.

    Article  Google Scholar 

  20. Masoudi FA, Rathore SS, Wang Y, Havranek EP, Curtis JP, Foody JM, et al. National patterns of use and effectiveness of angiotensin-converting enzyme inhibitors in older patients with heart failure and left ventricular systolic dysfunction. Circulation. 2004;110:724–31.

    Article  CAS  Google Scholar 

  21. Sanam K, Bhatia V, Bajaj NS, Gaba S, Morgan CJ, Fonarow GC, et al. Renin-angiotensin system inhibition and lower 30-day all-cause readmission in medicare beneficiaries with heart failure. Am J Med. 2016;129:1067–73.

    Article  CAS  Google Scholar 

  22. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128:e240–327.

    Google Scholar 

  23. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail. 2016;18:891–975.

    Article  Google Scholar 

  24. Cleland JG, Dargie HJ, Ball SG, Gillen G, Hodsman GP, Morton JJ, et al. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state. Br Heart J. 1985;54:305–12.

    Article  CAS  Google Scholar 

  25. Shirakabe A, Hata N, Kobayashi N, Shinada T, Tomita K, Tsurumi M, et al. Prognostic impact of acute kidney injury in patients with acute decompensated heart failure. Circ J. 2013;77:687–96.

    Article  CAS  Google Scholar 

  26. Yuan BH, Robinette JB, Conger JD. Effect of angiotensin II and norepinephrine on isolated rat afferent and efferent arterioles. Am J Physiol Physiol. 1990;258:F741–50.

    Article  CAS  Google Scholar 

  27. Schroten NF, Damman K, Hemmelder MH, Voors AA, Navis G, Gaillard CAJM, et al. Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction). Am Heart J. 2015;169(693–701):e3.

    Google Scholar 

  28. Voors AA, Davison BA, Felker GM, Ponikowski P, Unemori E, Cotter G, et al. Early drop in systolic blood pressure and worsening renal function in acute heart failure: renal results of Pre-RELAX-AHF. Eur J Heart Fail. 2011;13:961–7.

    Article  Google Scholar 

  29. Cotter G, Metra M, Davison BA, Jondeau G, Cleland JGF, Bourge RC, et al. Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe? Eur J Heart Fail. 2018;20:317–22.

    Article  CAS  Google Scholar 

  30. Hodsman GP, Isles CG, Murray GD, Usherwood TP, Webb DJ, Robertson JI. Factors related to first dose hypotensive effect of captopril: prediction and treatment. Br Med J (Clin Res Ed). 1983;286:832–4.

    Article  CAS  Google Scholar 

  31. Panzenbeck MJ, Loughnan CL, Madwed JB, Winquist RJ, Fogal SE. Captopril-induced hypotension is inhibited by the bradykinin blocker HOE-140 in Na(+)-depleted marmosets. Am J Physiol. 1995;269:H1221–8.

    PubMed  CAS  Google Scholar 

  32. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777–81.

    Article  CAS  Google Scholar 

  33. Zhang Q, Chen Y, Liu Q, Shan Q. Effects of renin–angiotensin–aldosterone system inhibitors on mortality, hospitalization, and diastolic function in patients with HFpEF. Herz. 2016;41:76–86.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Kameda Medical Center, Chiba, Japan

    Kenji Yoshioka, Shunsuke Kuroda & Akihiko Matsumura

  2. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Kenji Yoshioka, Shunsuke Kuroda & Kenzo Hirao

  3. Department of Cardiovascular Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan

    Yuya Matsue

  4. Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Yuya Matsue

  5. Department of Cardiology, Japanese Red Cross Musashino Hospital, Tokyo, Japan

    Tetsuo Yamaguchi

  6. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan

    Takeshi Kitai

  7. Department of Cardiology, The Sakakibara Heart Institute of Okayama, Okayama, Japan

    Nobuyuki Kagiyama

  8. Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan

    Takahiro Okumura

  9. Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan

    Keisuke Kida

  10. Department of Cardiology, Himeji Cardiovascular Center, Himeji, Japan

    Shogo Oishi

  11. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan

    Eiichi Akiyama

  12. Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan

    Satoshi Suzuki

  13. Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Masayoshi Yamamoto

Authors
  1. Kenji Yoshioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuya Matsue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tetsuo Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takeshi Kitai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nobuyuki Kagiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takahiro Okumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Keisuke Kida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shogo Oishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eiichi Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Satoshi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masayoshi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shunsuke Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Akihiko Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kenzo Hirao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuya Matsue.

Ethics declarations

Funding

This study was partly supported by a Grant-in-Aid for Early-Career Scientists (Grant no. 18K15862) and The Cardiovascular Research Fund, Tokyo, Japan.

Conflict of interest

Dr. Yuya Matsue has received an honorarium and grants from Otsuka Pharmaceutical Co. Kenji Yoshioka, Tetsuo Yamaguchi, Takeshi Kitai, Nobuyuki Kagiyama, Takahiro Okumura, Keisuke Kida, Shogo Oishi, Eiichi Akiyama, Satoshi Suzuki, Masayoshi Yamamoto, Shunsuke Kuroda, Akihiko Matsumura, and Kenzo Hirao have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 345 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshioka, K., Matsue, Y., Yamaguchi, T. et al. Safety and Prognostic Impact of Early Treatment with Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients with Acute Heart Failure. Am J Cardiovasc Drugs 19, 597–605 (2019). https://doi.org/10.1007/s40256-019-00355-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-019-00355-3

Search

Navigation