Skip to main content
SpringerLink
Log in

Angiotensin-converting-enzyme inhibitors in hemodynamic congestion: a meta-analysis of early studies

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Aim

Major clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in congestive heart failure (HF). Prior to these seminal findings hemodynamic effects of ACE inhibitors were examined in small studies. We aimed to review these studies systematically and meta-analyze the effects of ACE inhibitors on hemodynamics in HF.

Methods and results

We identified studies investigating the acute hemodynamic effect of ACE inhibitors in naïve patients with congestive heart failure by searching PubMed and the Cochrane Central Register of Controlled Trials. We extracted the changes in hemodynamic measures and their standard errors from study reports or calculated these values from baseline and post-medication measurements. Data were pooled using random effects models. In total, 41 studies with 46 independent cohorts consisting of 676 patients were included. ACE inhibitor treatment reduced pulmonary capillary wedge pressure by 7.3 (95% confidence interval 6.4–8.2) mmHg and right atrial pressure by 3.7 (95% confidence interval 1.3–6.1) mmHg in patients with HF. Cardiac index increased by 0.4 (95% confidence interval 0.2–0.6) ml/min/m2. Changes in hemodynamic measures were strongly connected to each other in weighted simple linear regression models.

Conclusion

Angiotensin-converting enzyme-inhibitors acutely reduced cardiac filling pressures and increased cardiac output in patients with congestive heart failure who were naïve for these drugs. These data indicate that ACE inhibitors exhibit a strong decongesting effect in congestive heart failure. In light of their impact on long-term prognosis, ACE inhibitors should also be considered as decongesting drugs in stable patients.

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
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ACE:

Angiotensin-converting enzyme

CI:

Cardiac index

HF:

Heart failure

IPD:

Individual patient data

MAP:

Mean arterial pressure

PCWP:

Pulmonary capillary wedge pressure

RAAS:

Renin–angiotensin–aldosterone system

RAP:

Right atrial pressure

SVR:

Systemic vascular resistance

References

  1. Ponikowski P, Voors AA, Anker SD et al (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 18:891–975

    Article  Google Scholar 

  2. Gheorghiade M, Follath F, Ponikowski P et al (2010) Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail 12:423–433

    Article  Google Scholar 

  3. Gotzmann M, Hauptmann S, Hogeweg M et al (2019) Hemodynamics of paradoxical severe aortic stenosis: insight from a pressure-volume loop analysis. Clin Res Cardiol. https://doi.org/10.1007/s00392-019-01423-z

    Article  PubMed  Google Scholar 

  4. Miller WL (2016) Fluid volume overload and congestion in heart failure: time to reconsider pathophysiology and how volume is assessed. Circ Heart Fail 9:e002922

    Article  CAS  Google Scholar 

  5. Hartupee J, Mann DL (2017) Neurohormonal activation in heart failure with reduced ejection fraction. Nat Rev Cardiol 14:30–38

    Article  CAS  Google Scholar 

  6. Kobayashi M, Rossignol P, Ferreira JP et al (2018) Prognostic value of estimated plasma volume in acute heart failure in three cohort studies. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1385-1

    Article  PubMed  Google Scholar 

  7. Ondetti MA, Rubin B, Cushman DW (1977) Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science 196:441–444

    Article  CAS  Google Scholar 

  8. Lipkin DP, Poole-Wilson PA (1985) Treatment of chronic heart failure: a review of recent drug trials. Br Med J (Clin Res Ed 291:993–996

    Article  CAS  Google Scholar 

  9. Group CTS (1987) Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 316:1429–1435

    Article  Google Scholar 

  10. Packer M (1992) The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 20:248–254

    Article  CAS  Google Scholar 

  11. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097

    Article  Google Scholar 

  12. Chatterjee K, Rouleau JL, Parmley WW (1982) Haemodynamic and myocardial metabolic effects of captopril in chronic heart failure. Br Heart J 47:233–238

    Article  CAS  Google Scholar 

  13. Nigri A, Mangieri E, Martuscelli E et al (1989) Hemodynamic and clinical effects of captopril in patients with severe congestive heart failure. Cardiologia 34:525–529

    CAS  PubMed  Google Scholar 

  14. Stevenson LW, Tillisch JH (1986) Maintenance of cardiac output with normal filling pressures in patients with dilated heart failure. Circulation 74:1303–1308

    Article  CAS  Google Scholar 

  15. Fallick C, Sobotka PA, Dunlap ME (2011) Sympathetically mediated changes in capacitance: redistribution of the venous reservoir as a cause of decompensation. Circ Heart Fail 4:669–675

    Article  Google Scholar 

  16. Investigators S, Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 325:293–302

    Article  Google Scholar 

  17. Investigators S, Yusuf S, Pitt B, Davis CE, Hood WB Jr, Cohn JN (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327:685–691

    Article  Google Scholar 

  18. Publication Committee for the VI (2002) Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287:1531–1540

    Google Scholar 

  19. Mitrovic V, Seferovic PM, Simeunovic D et al (2006) Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J 27:2823–2832

    Article  CAS  Google Scholar 

  20. Teerlink JR, Metra M, Felker GM et al (2009) Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet 373:1429–1439

    Article  CAS  Google Scholar 

  21. Ponikowski P, Mitrovic V, Ruda M et al (2014) A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure. Eur Heart J 35:431–441

    Article  CAS  Google Scholar 

  22. O’Connor CM, Starling RC, Hernandez AF et al (2011) Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med 365:32–43

    Article  Google Scholar 

  23. Packer M, O’Connor C, McMurray JJV et al (2017) Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure. N Engl J Med 376:1956–1964

    Article  CAS  Google Scholar 

  24. (2017) Novartis provides update on phase III study of RLX030 (serelaxin) in patients with acute heart failure. Press release of Novartis, Cambridge. https://www.novartis.com/news/media-releases/novartis-provides-update-phase-iii-study-rlx030-serelaxin-patients-acute-heart. Accessed 1 Oct 2018

  25. Zile MR, Bennett TD, St John Sutton M et al (2008) Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation 118:1433–1441

    Article  Google Scholar 

  26. IntHout J, Ioannidis JP, Borm GF, Goeman JJ (2015) Small studies are more heterogeneous than large ones: a meta-meta-analysis. J Clin Epidemiol 68:860–869

    Article  Google Scholar 

Download references

Funding

Universitätsklinikum Schleswig–Holstein, Universität zu Lübeck, and Herzzentrum Leipzig.

Author information

Author notes

  1. Cor de Wit and Reinhard Vonthein shared senior authorship.

Authors and Affiliations

  1. Medizinische Klinik II/Kardiologie, Angiologie, Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Alexander Jobs, Suzanne de Waha-Thiele & Ingo Eitel

  2. German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany

    Alexander Jobs, Suzanne de Waha-Thiele, Ingo Eitel & Cor de Wit

  3. Klinik für Innere Medizin/Kardiologie, Herzzentrum Leipzig-Universitätsklinik, Strümpellstr. 39, 04289, Leipzig, Germany

    Alexander Jobs & Holger Thiele

  4. Medizinische Klinik I/Kardiologie, Angiologie und internistische Intensivmedizin, RWTH Aachen, Aachen, Germany

    Amr Abdin

  5. Institut für Physiologie, Universität zu Lübeck, Lübeck, Germany

    Cor de Wit

  6. Institut für Medizinische Biometrie und Statistik, ZKS Lübeck, Universität zu Lübeck, Lübeck, Germany

    Reinhard Vonthein

Authors
  1. Alexander Jobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amr Abdin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suzanne de Waha-Thiele
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ingo Eitel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Holger Thiele
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cor de Wit
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Reinhard Vonthein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander Jobs.

Ethics declarations

Conflict of interest

No conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 2736 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jobs, A., Abdin, A., de Waha-Thiele, S. et al. Angiotensin-converting-enzyme inhibitors in hemodynamic congestion: a meta-analysis of early studies. Clin Res Cardiol 108, 1240–1248 (2019). https://doi.org/10.1007/s00392-019-01456-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-019-01456-4

Keywords

Search

Navigation