Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial.
Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF.Objective: To determine the...
| Publicado en: | JAMA: Journal of the American Medical Association Vol. 320; no. 17; pp. 1764 - 1774 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
American Medical Association
11/6/2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=132918582&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 132918582 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00987484 AMA jtl: JAMA: Journal of the American Medical Association issn: 00987484 maglogo: N pubinfo: dt: 11/6/2018 vid: 320 iid: 17 pid: 30 pub: American Medical Association place: Chicago, Illinois artinfo: ui: 132918582 132918582 NLM30398602 132918582 10.1001/jama.2018.14852 NLM30398602 132918582 ppf: 1764 ppct: 10 formats: tig: atl: Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial. aug: au: Borlaug, Barry A. Anstrom, Kevin J. Lewis, Gregory D. Shah, Sanjiv J. Levine, James A. Koepp, Gabe A. Givertz, Michael M. Felker, G. Michael LeWinter, Martin M. Mann, Douglas L. Margulies, Kenneth B. Smith, Andrew L. Tang, W. H. Wilson Whellan, David J. Chen, Horng H. Davila-Roman, Victor G. McNulty, Steven Desvigne-Nickens, Patrice Hernandez, Adrian F. Braunwald, Eugene affil: Mayo Clinic, Rochester, Minnesota sug: subj: Heart Failure Drug Therapy Nitrites Therapeutic Use Exercise Tolerance Drug Effects Nitrites Pharmacodynamics Male Female Double-Blind Studies Nitrites Adverse Effects Crossover Design Heart Failure Physiopathology Stroke Volume Exercise Test Middle Age Inorganic Chemicals Therapeutic Use Administration, Inhalation Exercise Tolerance Physiology Human Treatment Failure Aged Inorganic Chemicals Pharmacodynamics Oxygen Consumption Validation Studies Comparative Studies Evaluation Research Multicenter Studies Randomized Controlled Trials Questionnaires Middle Aged: 45-64 years Aged: 65+ years Male Female ab: Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF.Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF.Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018.Interventions: Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks.Main Outcomes and Measures: The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks.Results: Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase.Conclusions and Relevance: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity.Trial Registration: ClinicalTrials.gov Identifier: NCT02742129. pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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