Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial.

BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. RESULTS: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

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

BACKGROUND: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. METHODS AND RESULTS: This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). CONCLUSIONS: A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s.

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

OBJECTIVES: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. METHODS: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. RESULTS: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ±â€Š40.4 versus 16.2 ±â€Š26.7 mg, P = 0.09). CONCLUSION: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. CLINICAL TRIALS REGISTRATION NUMBER: NCT00971165.