Spironolactone and Resistant Hypertension in Heart Failure with Preserved Ejection Fraction

Patrick Rossignol, Brian Lee Claggett, Jiankang Liu, Orly Vardeny, Bertram Pitt, Faiez Zannad, Scott Solomon

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)407-414
Number of pages8
JournalAmerican journal of hypertension
Issue number4
StatePublished - Mar 10 2018

Bibliographical note

Funding Information:
The TOPCAT trial was funded by the National Heart, Lung, and Blood Institute.

Publisher Copyright:
© 2018 American Journal of Hypertension, Ltd.


  • Blood pressure
  • heart failure with preserved ejection fraction
  • hypertension
  • randomized trial
  • resistant hypertension
  • spironolactone.


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