Flávio D Fuchs1, Luiz C N Scala2, José F Vilela-Martin3, Paul K Whelton4, Carlos E Poli-de-Figueiredo5, Ricardo Pereira E Silva6, Miguel Gus1, Luiz A Bortolotto7, Fernanda M Consolim-Colombo7, Rosane P Schlatter8, José E Cesarino9, Iran Castro10, José A Figueiredo Neto11, Hilton Chaves12, André A Steffens13, João G Alves14, Andréa A Brandão15, Marcos R de Sousa16, Paulo C Jardim17, Leila B Moreira8, Roberto S Franco18, Marco M Gomes19, Abrahão Afiune Neto20, Felipe C Fuchs1, Dario C Sobral Filho21, Antônio C Nóbrega22, Fernando Nobre23, Otávio Berwanger24, Sandra C Fuchs25. 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. 2. Hospital Universitário Júlio Müller, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil. 3. Faculdade de Medicina São José Do Rio Preto, São José do Rio Preto, SP, Brazil. 4. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. 5. Faculdade de Medicina Hospital São Lucas, PUCRS, Porto Alegre, RS, Brazil. 6. Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brazil. 7. Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP, Brazil. 8. Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande Do Sul, Porto Alegre, RS, Brazil. 9. Faculdade de Ciências Farmacêuticas, USP Ribeirão Preto, Ribeirão Prêto, SP, Brazil. 10. Instituto de Cardiologia, Av. Princesa Isabel, Porto Alegre, RS, 395, Brazil. 11. Hospital Universitário Universidade Federal do Maranhão, São Luís, MA, Brazil. 12. Universidade Federal de Pernambuco, Recife, PE, Brazil. 13. Universidade Federal de Pelotas, Pelotas, RS, 96010-610, Brazil. 14. Instituto de Medicina Integral Prof Fernando Figueira, Recife, PE, Brazil. 15. Universidade Do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. 16. Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. 17. Hospital das Clínicas de Goiânia, Universidade Federal de Goiás, Goiânia, GO, Brazil. 18. Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil. 19. Hospital do Coração de Alagoas, Maceió, AL, Brazil. 20. Anis Rassi Hospital, Goiânia, GO, Brazil. 21. Hospital Universitário Procape, Recife, PE, Brazil. 22. Hospital Universitário Antônio Pedro, UFF, Niterói, RJ, Brazil. 23. Faculdade de Medicina de Ribeirão Preto, USP Ribeirão Preto, Ribeirão Prêto, SP, Brazil. 24. Instituto de Pesquisa, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. 25. 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. sfuchs@hcpa.edu.br.
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.
RCT Entities:
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.
Entities:
Keywords:
Amiloride; Chlorthalidone; Diabetes; Drug treatment; Hypertension; Losartan
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