A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial

Flávio D Fuchs, Sandra C Fuchs, Leila B Moreira, Miguel Gus, Antônio C Nóbrega, Carlos E Poli-de-Figueiredo, Décio Mion, Luiz Bortolotto, Fernanda Consolim-Colombo, Fernando Nobre, Eduardo Barbosa Coelho, José F Vilela-Martin, Heitor Moreno Jr, Evandro José Cesarino, Roberto Franco, Andréa Araujo Brandão, Marcos R de Sousa, Antônio Luiz Pinho Ribeiro, Paulo Cesar Jardim, Abrahão Afiune Neto, Luiz César N Scala, Marco Mota, Hilton Chaves, João Guilherme Alves, Dario C Sobral Filho, Ricardo Pereira e Silva, José A Figueiredo Neto, Maria Cláudia Irigoyen, Iran Castro, André Avelino Steffens, Rosane Schlatter, Renato Bandeira de Mello, Francisca Mosele, Flávia Ghizzoni, Otávio Berwanger, Flávio D Fuchs, Sandra C Fuchs, Leila B Moreira, Miguel Gus, Antônio C Nóbrega, Carlos E Poli-de-Figueiredo, Décio Mion, Luiz Bortolotto, Fernanda Consolim-Colombo, Fernando Nobre, Eduardo Barbosa Coelho, José F Vilela-Martin, Heitor Moreno Jr, Evandro José Cesarino, Roberto Franco, Andréa Araujo Brandão, Marcos R de Sousa, Antônio Luiz Pinho Ribeiro, Paulo Cesar Jardim, Abrahão Afiune Neto, Luiz César N Scala, Marco Mota, Hilton Chaves, João Guilherme Alves, Dario C Sobral Filho, Ricardo Pereira e Silva, José A Figueiredo Neto, Maria Cláudia Irigoyen, Iran Castro, André Avelino Steffens, Rosane Schlatter, Renato Bandeira de Mello, Francisca Mosele, Flávia Ghizzoni, Otávio Berwanger

Abstract

Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.

Methods/design: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.

Discussion: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil.

Clinical trials registration number: ClinicalTrials.gov: NCT00971165.

Figures

Figure 1
Figure 1
Flow chart of the PREVER-Treatment trial, describing the selection, randomization and follow-up process.
Figure 2
Figure 2
Summary of the PREVER-Treatment trial key practical aspects.
Figure 3
Figure 3
PREVER-Treatment trial cardiovascular outcomes.

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Source: PubMed

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