Apparent Treatment-Resistant Hypertension Across the Spectrum of Heart Failure Phenotypes in the Swedish HF Registry

Jackson, Alice; Benson, Lina; Savarese, Gianluigi; Hage, Camilla; Jhund, Pardeep S.; Petrie, Mark C; Dahlström, Ulf; McMurray, John J.V.; Lund, Lars H.

doi:10.1016/j.jchf.2022.04.006

Cited by 7 publications

(12 citation statements)

References 28 publications

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“…8,12,13,16–18,27 Also consistent with observational and trial data, DELIVER participants with aTRH tended to have a more adverse metabolic profile (higher prevalence of diabetes, dyslipidemia, and obesity) and kidney profile, were less likely to have comorbid atrial fibrillation, and exhibited lower NT-proBNP levels (likely attributable to body mass index–related and atrial fibrillation–related effects). 16,17,27,28 These comorbidities might in part drive hypertension by mechanisms such as diabetes-related vascular and neurohormonal dysfunction, kidney disease–related volume excess, and obesity-related hyperaldosteronism. 8,29,30…”

Section: Discussionsupporting

confidence: 59%

“…Despite the exclusion of patients with severely uncontrolled (≥180 mm Hg) systolic BP and advanced chronic kidney disease (estimated glomerular filtration rate <25 mL·min·1.73 m 2 ), 8 the prevalence of aTRH in DELIVER was broadly commensurate with observations from contemporary epidemiologic studies and previous HF clinical trials. 8,12,13,16–18,27 Also consistent with observational and trial data, DELIVER participants with aTRH tended to have a more adverse metabolic profile (higher prevalence of diabetes, dyslipidemia, and obesity) and kidney profile, were less likely to have comorbid atrial fibrillation, and exhibited lower NT-proBNP levels (likely attributable to body mass index–related and atrial fibrillation–related effects). 16,17,27,28 These comorbidities might in part drive hypertension by mechanisms such as diabetes-related vascular and neurohormonal dysfunction, kidney disease–related volume excess, and obesity-related hyperaldosteronism.…”

Section: Discussionsupporting

confidence: 59%

“…Despite the exclusion of patients with severely uncontrolled (≥180 mm Hg) systolic BP and advanced chronic kidney disease (estimated glomerular filtration rate <25 mL•min•1.73 m 2 ), 8 the prevalence of aTRH in DELIVER was broadly commensurate with observations from con-temporary epidemiologic studies and previous HF clinical trials. 8,12,13,[16][17][18]27 Also consistent with observational and trial data, DELIVER participants with aTRH tended to have a more adverse metabolic profile (higher prevalence of diabetes, dyslipidemia, and obesity) and kidney profile, were Values shown represent the placeboadjusted mean change in systolic blood pressure (SBP) from baseline to month 1 (top) and from baseline to all values obtained postbaseline (bottom) throughout the trial duration. *Placeboadjusted SBP effects of dapagliflozin for each subgroup were estimated using a linear mixed-effects model using all SBP measurements throughout trial follow-up, including an interaction term for effect modification by baseline blood pressure (BP) category.…”

Section: Discussionmentioning

confidence: 53%

“…Third, although controlled aTRH has been defined by some as requiring ≥4 antihypertensive drugs to achieve target BP, 8 we elected not to focus on this group in this analysis due to the possibility of confounding by indication (ie, many patients may have been prescribed key pharmacotherapies for HF rather than hypertension). Fourth, consistent with previous analyses, 17,27 we did not evaluate participants without hypertension as a unique subgroup. Nearly all DELIVER participants had a previous diagnosis of hypertension or were on at least one antihypertensive medication.…”

Section: Study Limitationsmentioning

confidence: 73%

“…8,14,15 In HF, aTRH appears to be especially common among patients with HF with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF). [16][17][18] In populations of aTRH and chronic kidney disease, 19 sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to improve BP control and reduce the need for additional antihypertensive agents. 20 Previous analyses of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) have demonstrated that the benefits of SGLT2i in HFmrEF and HFpEF are consistent irrespective of baseline BP, and associated with modest BP-lowering effects (≈2 mm Hg) in this population.…”

mentioning

confidence: 99%

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Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The DELIVER Trial

Ostrominski,

Vaduganathan,

Selvaraj

et al. 2023

Circulation

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BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is prevalent and associated with adverse outcomes in heart failure with mildly reduced or preserved ejection fraction. Less is known about the potential role of sodium-glucose co-transporter 2 inhibition in this high-risk population. In this post hoc analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), we evaluated clinical profiles and treatment effects of dapagliflozin among participants with aTRH. METHODS: DELIVER participants were categorized on the basis of baseline blood pressure (BP), with aTRH defined as BP ≥140/90 mm Hg (≥130/80 mm Hg if diabetes) despite treatment with 3 antihypertensive drugs including a diuretic. Nonresistant hypertension was defined as BP above threshold but not meeting aTRH criteria. Controlled BP was defined as BP under threshold. Incidence of the primary outcome (cardiovascular death or worsening heart failure event), key secondary outcomes, and safety events was assessed by baseline BP category. RESULTS: Among 6263 DELIVER participants, 3766 (60.1%) had controlled BP, 1779 (28.4%) had nonresistant hypertension, and 718 (11.5%) had aTRH at baseline. Participants with aTRH had more cardiometabolic comorbidities and tended to have higher left ventricular ejection fraction and worse kidney function. Rates of the primary outcome were 8.7 per 100 patient-years in those with controlled BP, 8.5 per 100 patient-years in the nonresistant hypertension group, and 9.5 per 100 patient-years in the aTRH group. Relative treatment benefits of dapagliflozin versus placebo on the primary outcome were consistent across BP categories ( P interaction =0.114). Participants with aTRH exhibited the greatest absolute reduction in the rate of primary events with dapagliflozin (4.1 per 100 patient-years) compared with nonresistant hypertension (2.7 per 100 patient-years) and controlled BP (0.8 per 100 patient-years). Irrespective of assigned treatment, participants with aTRH experienced a higher rate of reported vascular events, including myocardial infarction and stroke, over study follow-up. Dapagliflozin modestly reduced systolic BP (by ≈1 to 3 mm Hg) without increasing risk of hypotension, hypovolemia, or other serious adverse events, irrespective of BP category, but did not improve the proportion of participants with aTRH attaining goal BP over time. CONCLUSIONS: aTRH was identified in >1 in 10 patients with heart failure and left ventricular ejection fraction >40% in DELIVER. Dapagliflozin consistently improved clinical outcomes and was well-tolerated, including among those with aTRH. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03619213.

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