A Randomized trial assessing Efficacy and safety of Mineralocorticoid receptor Antagonist therapy compared to Standard antihypertensive Therapy in hypErtension with low Renin (REMASTER): rationale and study design

J Hum Hypertens. 2024 Sep;38(9):663-668. doi: 10.1038/s41371-024-00931-4. Epub 2024 Jul 18.

Abstract

Low-renin hypertension affects 1 in 4 people with hypertension, but the optimal management of this condition is not known. We hypothesize that a large proportion of people with low-renin hypertension is mediated by excess mineralocorticoid receptor (MR) activation and that targeted treatment with an MR antagonist (MRA) will be beneficial. This randomized, single-blinded, titration-to-effect aims to investigate whether targeted treatment in low-renin hypertension with MRA is better compared to standard antihypertensives in terms of blood pressure control and end-organ protection. Adults with hypertension, who are treatment naïve or are receiving up to two antihypertensive agents and have a low direct renin concentration <10 mU/L will be included. Participants with severe hypertension, a secondary cause of hypertension, pregnant, breastfeeding, with moderate-severe cardiovascular and chronic kidney disease, or on medications that confound interpretation of the plasma direct renin or aldosterone concentrations will be excluded. Eligible participants will be randomized 1:1 to either MRA therapy (spironolactone) or standard anti-hypertensive therapy (perindopril+/- amlodipine) for 48 weeks. Anti-hypertensives will be up-titrated every 12 weeks until target blood pressure is achieved. The primary objective will be to determine the total defined daily dose of antihypertensives required to achieve the target blood pressure and change in mean clinic systolic blood pressure at week 48. Current hypertension guidelines do not have specific recommendations for the choice of anti-hypertensive medications for people with low-renin hypertension. The results of this trial could guide future hypertension guidelines.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Antihypertensive Agents* / adverse effects
  • Antihypertensive Agents* / therapeutic use
  • Blood Pressure / drug effects
  • Female
  • Humans
  • Hypertension* / diagnosis
  • Hypertension* / drug therapy
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists* / therapeutic use
  • Randomized Controlled Trials as Topic
  • Renin* / antagonists & inhibitors
  • Renin* / blood
  • Single-Blind Method
  • Spironolactone / adverse effects
  • Spironolactone / therapeutic use
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Renin
  • Spironolactone