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Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial

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A Correction to this article was published on 01 March 2021

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Abstract

Aims

To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus.

Methods

In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30–70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion.

Results

Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment.

Conclusions

Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension.

Trial registration

Clinical trials registration number: NCT00971165

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Availability of data and material (data transparency)

All datasets on which the conclusions of the paper rely will be available to in publicly available repository (https://www.lume.ufrgs.br/).

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Funding

This study was funded by grants from the Department of Science and Technology (DECIT), Health Ministry; National Council of Research (CNPq) and Agency for Funding of Studies and Projects (FINEP; Number 01080606/01), Science and Technology Ministry; Funding of Incentive to Research of Hospital de Clinicas de Porto Alegre (FIPE-HCPA: GPPG 08-621), all in Brazil. The sponsors had no participation in the design and conduct of the study, preparation and approval of the manuscript.

Author information

Authors and Affiliations

  1. Division of Cardiology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande Do Sul, INCT PREVER, CPC, 5º. and Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil

    Flávio D. Fuchs, Miguel Gus, Felipe C. Fuchs & Sandra C. Fuchs

  2. Hospital Universitário Júlio Müller, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil

    Luiz C. N. Scala

  3. Faculdade de Medicina São José Do Rio Preto, São José do Rio Preto, SP, Brazil

    José F. Vilela-Martin

  4. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA

    Paul K. Whelton

  5. Faculdade de Medicina Hospital São Lucas, PUCRS, Porto Alegre, RS, Brazil

    Carlos E. Poli-de-Figueiredo

  6. Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brazil

    Ricardo Pereira E Silva

  7. Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP, Brazil

    Luiz A. Bortolotto & Fernanda M. Consolim-Colombo

  8. Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande Do Sul, Porto Alegre, RS, Brazil

    Rosane P. Schlatter & Leila B. Moreira

  9. Faculdade de Ciências Farmacêuticas, USP Ribeirão Preto, Ribeirão Prêto, SP, Brazil

    José E. Cesarino

  10. Instituto de Cardiologia, Av. Princesa Isabel, Porto Alegre, RS, 395, Brazil

    Iran Castro

  11. Hospital Universitário Universidade Federal do Maranhão, São Luís, MA, Brazil

    José A. Figueiredo Neto

  12. Universidade Federal de Pernambuco, Recife, PE, Brazil

    Hilton Chaves

  13. Universidade Federal de Pelotas, Pelotas, RS, 96010-610, Brazil

    André A. Steffens

  14. Instituto de Medicina Integral Prof Fernando Figueira, Recife, PE, Brazil

    João G. Alves

  15. Universidade Do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Andréa A. Brandão

  16. Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Marcos R. de Sousa

  17. Hospital das Clínicas de Goiânia, Universidade Federal de Goiás, Goiânia, GO, Brazil

    Paulo C. Jardim

  18. Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil

    Roberto S. Franco

  19. Hospital do Coração de Alagoas, Maceió, AL, Brazil

    Marco M. Gomes

  20. Anis Rassi Hospital, Goiânia, GO, Brazil

    Abrahão Afiune Neto

  21. Hospital Universitário Procape, Recife, PE, Brazil

    Dario C. Sobral Filho

  22. Hospital Universitário Antônio Pedro, UFF, Niterói, RJ, Brazil

    Antônio C. Nóbrega

  23. Faculdade de Medicina de Ribeirão Preto, USP Ribeirão Preto, Ribeirão Prêto, SP, Brazil

    Fernando Nobre

  24. Instituto de Pesquisa, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil

    Otávio Berwanger

Authors
  1. Flávio D. Fuchs
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  2. Luiz C. N. Scala
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  3. José F. Vilela-Martin
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  4. Paul K. Whelton
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  5. Carlos E. Poli-de-Figueiredo
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  6. Ricardo Pereira E Silva
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  7. Miguel Gus
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  8. Luiz A. Bortolotto
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  9. Fernanda M. Consolim-Colombo
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  12. Iran Castro
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  13. José A. Figueiredo Neto
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  14. Hilton Chaves
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  17. Andréa A. Brandão
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  18. Marcos R. de Sousa
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  19. Paulo C. Jardim
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  20. Leila B. Moreira
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  21. Roberto S. Franco
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  22. Marco M. Gomes
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  23. Abrahão Afiune Neto
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  26. Antônio C. Nóbrega
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  27. Fernando Nobre
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  28. Otávio Berwanger
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  29. Sandra C. Fuchs
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Contributions

SCF and FDF have full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. All of the authors made substantial contributions to the conception of the study, and/or the acquisition, analysis, or interpretation of study data, and/or drafting or revision of the manuscript, and all authors approved the final version of the manuscript and agreed to be accountable for all aspects of the study.

Corresponding author

Correspondence to Sandra C. Fuchs.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the Hospital de Clinicas de Porto Alegre (GPPG 08-621), which is accredited by the Office of Human Research Protections as an Institutional Review Board, and by the ethics committee at each medical center. The PREVER-Treatment trial was conducted in 21 academic medical centers in Brazil, and was approved by the Research Ethics Board of each participant institution.

Informed consent

Eligible participants were enrolled in the trial and gave written informed consent prior to their inclusion in the study.

Additional information

Managed by Massimo Porta.

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Hilton Chaves, Abrahão Afiune Neto: in memorial.

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Fuchs, F.D., Scala, L.C.N., Vilela-Martin, J.F. et al. Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial. Acta Diabetol 58, 215–220 (2021). https://doi.org/10.1007/s00592-020-01611-8

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  • DOI: https://doi.org/10.1007/s00592-020-01611-8

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