Spironolactone and Resistant Hypertension in Heart Failure With Preserved Ejection Fraction

Am J Hypertens. 2018 Mar 10;31(4):407-414. doi: 10.1093/ajh/hpx210.


Background: Recent evidence suggests that the mineralocorticoid receptor antagonist spironolactone should be the preferred fourth-line antihypertensive treatment in resistant hypertension (RHTN). Whether spironolactone improves blood pressure (BP) control in heart failure with preserved ejection fraction (HFpEF) and RHTN is unknown.

Methods: We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs. placebo. We evaluated the effects of spironolactone vs. placebo on BP reduction in this group and related this to the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure.

Results: We identified 403 participants in the Americas with RHTN. Compared to people without RHTN, those with RHTN were more frequently women, non-White, diabetics, with a higher left ventricular ejection fraction and body mass index, and a lower hemoglobin concentration. In the RHTN group, spironolactone resulted in a decrease of SBP: -6.1 (-8.9, -3.3); P < 0.001 and diastolic BP: -2.9 (-4.6, -1.2); P = 0.001 mm Hg during the first 8 months. BP became controlled after 4 weeks in 63% of patients receiving spironolactone vs. 46% receiving placebo (P = 0.003), with similar responses at 8 weeks, 4 and 8 months. Patients with RHTN derived similar overall benefit from spironolactone on the primary outcomes as those without.

Conclusions: In HFpEF patients with RHTN, spironolactone lowered BP substantially and was associated with similar benefit as those without RHTN.

Clinical trials registration: Trial Number NCT00094302 (ClinicalTrials.gov identifier).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Argentina
  • Blood Pressure / drug effects*
  • Brazil
  • Canada
  • Drug Resistance
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / mortality
  • Heart Failure / physiopathology*
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Hypertension / physiopathology
  • Male
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Risk Factors
  • Spironolactone / adverse effects
  • Spironolactone / therapeutic use*
  • Stroke Volume*
  • Time Factors
  • Treatment Outcome
  • United States
  • Ventricular Function, Left*


  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone

Associated data

  • ClinicalTrials.gov/NCT00094302