Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

Abstract

BackgroundBlood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.MethodsThis is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, 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 sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.DiscussionThe early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial RegistrationClinical Trials NCT00970931.

Predicting the Risk of Incident Hypertension in a Korean Middle‐Aged Population: Korean Genome and Epidemiology Study

“…Recent clinical trials indicate that suitable interventions such as lifestyle modification programs or medications are effective strategies for individuals with prehypertension . However, such intervention programs may incur high costs that place a burden on patients, their families, and the national health care system.…”

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER‐Prevention Randomized Clinical Trial

“…All participants signed an informed consent form prior to participation in the trial. This study was registered at http://ClinicalTrials.gov (NCT00970931) and ReBEC (Registro Brasileiro de Ensaios Clinicos), and its detailed rationale and methods have been published elsewhere …”

Antihypertensive Therapy Versus Alternative Therapeutic Options for Prehypertension: an evidence-based Approach

“…The utility of pharmacologic agents in primary prevention of CV events in patients with pre-HTN is further being tested [46]. More randomized placebo control trials with perhaps specific BP goal/targets and longer follow-up are needed to establish the utility of therapeutic modalities, particularly pharmacologic interventions for safely reducing BP and improving target organ damage, CV morbidity and mortality in patients with pre-HTN.…”