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

Abstract

BackgroundPrehypertension 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 ResultsThis 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).ConclusionsA 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.

Do thiazide diuretics reduce central systolic blood pressure in hypertension?

“…In addition, the influence of antihypertensive therapy leading to improvements in CSBP of patients with stage 1 hypertension cannot be excluded. 22 showed that the use of a fixed combination of low-dose chlorthalidone and amiloride also produced a substantial and highly significant reduction in the incidence of hypertension and a reduction in left ventricular mass in patients with prehypertension, These authors concluded that the use of low-dose diuretics in patients with prehypertension might be an effective option to reduce the burden of hypertension and its cardiovascular consequences.…”

Prehypertension: What to Do?

“…26 The study showed significant reduction in the risk of progression to manifest hypertension by 34.4%. The PREVER prevention trial 27 is the combination of chlorthalidone and amiloride in prehypertensive patients that effectively reduces the risk of incident hypertension and beneficially affects LV mass. After 18 months, the incidence of hypertension was 11.7% in the diuretic arm vs 19.5% in the placebo arm.…”

Non-pharmacological interventions for the prevention of hypertension in low-income and middle-income countries: protocol for a systematic review and meta-analysis

“…Some medications have also been tested through randomised controlled trials (RCTs) in the prehypertensive population to prevent the high prevalence of hypertension. 16 …”