Effect of Vericiguat on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction (HFpEF) | Cardiology | JN Learning | AMA Ed Hub [Skip to Content]
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Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection FractionThe VITALITY-HFpEF Randomized Clinical Trial

Educational Objective
To learn the effect of treatment with vericiguat on quality of life and functional limitations in patients with heart failure with preserved ejection fraction.
1 Credit CME
Key Points

Question  Does vericiguat improve the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure and preserved ejection fraction (HFpEF)?

Findings  In this randomized clinical trial, 789 patients with HFpEF after recent HF decompensation were randomized to receive vericiguat, 15 mg/d; vericiguat, 10 mg/d; or placebo. After 24 weeks, the mean changes in the KCCQ PLS (range, 0-100; higher values indicate better functioning) were 5.5 points in the 15-mg/d vericiguat group, 6.5 points in the 10-mg/d vericiguat group, and 6.9 points in the placebo group; differences between either vericiguat dosage and placebo were not statistically significant.

Meaning  Vericiguat did not improve the KCCQ PLS at 24 weeks in patients with HFpEF.

Abstract

Importance  Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life.

Objective  To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Design, Setting, and Participants  Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019.

Interventions  Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1.

Main Outcomes and Measures  The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks.

Results  Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro–brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was −1.5 (95% CI, −5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was −0.5 (95% CI, −4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was −5.5 m (95% CI, −19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was −1.8 m (95% CI, −16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively.

Conclusions and Relevance  Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ.

Trial Registration  ClinicalTrials.gov Identifier: NCT03547583

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Article Information

Corresponding Author: Paul W. Armstrong, MD, 4-120 Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada (paul.armstrong@ualberta.ca).

Accepted for Publication: August 6, 2020.

Correction: This article was corrected for errors in figure labeling on February 2, 2021.

Author Contributions: Dr Armstrong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Armstrong, Lam, Anstrom, Ezekowitz, Hernandez, O’Connor, Pieske, Ponikowski, Shah, Solomon, Voors, Vlajnic, Carvalho, Bamber, Blaustein, Roessig, Butler.

Acquisition, analysis, or interpretation of data: Armstrong, Lam, Anstrom, Ezekowitz, Hernandez, O’Connor, Pieske, Ponikowski, Voors, She, Vlajnic, Carvalho, Bamber, Blaustein, Roessig, Butler.

Drafting of the manuscript: Armstrong, Lam, Anstrom, Ezekowitz, She, Vlajnic, Roessig, Butler.

Critical revision of the manuscript for important intellectual content: Armstrong, Lam, Anstrom, Ezekowitz, Hernandez, O’Connor, Pieske, Ponikowski, Shah, Solomon, Voors, Vlajnic, Carvalho, Bamber, Blaustein, Roessig, Butler.

Statistical analysis: Armstrong, Anstrom, She, Vlajnic, Bamber.

Obtained funding: Armstrong, Blaustein.

Administrative, technical, or material support: Carvalho, Bamber, Butler.

Supervision: Armstrong, Anstrom, O’Connor, Pieske, Ponikowski, Bamber, Blaustein, Roessig, Butler.

Conflict of Interest Disclosures: Dr Armstrong reported receiving personal fees from Merck and Bayer during the conduct of the study as well as grants from Sanofi-Aventis Recherche & Developpement, Boehringer Ingelheim, and CSL Limited and personal fees from AstraZeneca and Novartis. Dr Lam reported receiving personal fees from Bayer during the conduct of the study as well as grants from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma and personal fees from Abbott Diagnostics, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Biofourmis, Boehringer Ingelheim, Boston Scientific, Corvia Medical, Cytokinetics, Darma, Eko.ai, JanaCare, Janssen Research & Development, Medtronic, Menarini Group, Merck, MyoKardia, Novartis, Novo Nordisk, Radcliffe Group, Roche Diagnostics, Stealth BioTherapeutics, The Corpus, Vifor Pharma, and WebMD. In addition, Dr Lam has a patent pending on a method for diagnosis and prognosis of chronic heart failure (PCT/SG2016/050217) and a patent issued for a clinical workflow that recognizes and analyses 2D and Doppler echocardiogram images for automated cardiac measurements and diagnosis, prediction, and prognosis of heart disease (16/216,929). Dr Lam is also cofounder and nonexecutive director of EKo.ai Pte Ltd. Dr Ezekowitz reported receiving personal fees from Bayer and Merck during the conduct of the study as well as grants and personal fees from American Regent, Novartis, AstraZeneca, Boehringer Ingelheim, Amgen, and Cytokinetics (additional disclosures available online at https://thecvc.ca). Dr Hernandez reported receiving personal fees from Bayer and Merck during the conduct of the study as well as grants and personal fees from AstraZeneca and Novartis and personal fees from Amgen and Cytokinetics. Dr O’Connor reported receiving consulting for Bayer, Bristol Myers Squibb Foundation, and Dey. Dr Pieske reported receiving personal fees from Merck and Bayer during the conduct of the study as well as personal fees from Novartis, Servier, Medscape, and Bristol Myers Squibb. Dr Ponikowski reported receiving personal fees from Merck during the conduct of the study as well as receiving personal fees from and participating in clinical trials for Amgen, Boehringer Ingelheim, Servier, AstraZeneca, RenalGuardSolution, and Cibiem; receiving grants and personal fees from and participating in clinical trials for Vifor Pharma; and receiving personal fees from Pfizer and Respicardia. Dr Shah reported receiving personal fees from Bayer during the conduct of the study as well as grants and personal fees from Actelion, AstraZeneca, Novartis, and Pfizer; grants from Corvia; and personal fees from Cyclerion, Amgen, Boehringer Ingelheim, Cardiora, Cytokinetics, MyoKardia, Merck, Shifamed, Eisai, Ionis, Novo Nordisk, Sanofi, and Tenax. Dr Solomon reported receiving personal fees from Bayer during the conduct of the study as well as grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, Neurotronik, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Respicardia, Sanofi Pasteur, and Theracos and personal fees from Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Sanofi Pasteur, Tenaya, Dinaqor, Tremeau, CellProThera, and Moderna. Dr Voors reported receiving personal fees from Merck and Bayer during the conduct of the study as well as personal fees from AstraZeneca, Cytokinetics, Novartis, and MyoKardia and grants and personal fees from Boehringer Ingelheim, Novo Nordisk, and Roche Diagnostics. Ms Vlajnic is an employee of Bayer. Dr Carvalho is an employee of Bayer. Mr Bamber is an employee of Bayer. Dr Blaustein reported receiving personal fees from Merck during the conduct of the study and is an employee of Merck. Dr Roessig is an employee of Bayer. Dr Butler reported receiving personal fees from Bayer and Merck during the conduct of the study as well as personal fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, BerlinCures, Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Limited, and Vifor. No other disclosures were reported.

Funding/Support: Funding for this research was provided by Bayer and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc.

Role of the Funder/Sponsor: The sponsors, in collaboration with the steering committee, participated in the design and conduct of the study and the collection, management, analysis, and interpretation of the data. Preparation, review, and approval of the manuscript and the decision to submit the manuscript for publication were undertaken by the steering committee. The sponsors did not have the right to veto publication or to control the decision regarding the choice of journal for submission.

Group Information: The members of the VITALITY-HFpEF Study Group are listed in eAppendix 1 in Supplement 3.

Data Sharing Statement: See Supplement 4.

Additional Contributions: Elizabeth E. S. Cook, BA, an employee of the Duke Clinical Research Institute, and Cecilia Freitas, MD, MSc, PhD, an employee of Bayer, provided editorial assistance. No compensation outside of their regular salaries was received.

References
1.
Dunlay  SM , Roger  VL , Redfield  MM .  Epidemiology of heart failure with preserved ejection fraction.   Nat Rev Cardiol. 2017;14(10):591-602. doi:10.1038/nrcardio.2017.65PubMedGoogle ScholarCrossref
2.
Gheorghiade  M , Marti  CN , Sabbah  HN ,  et al; Academic Research Team in Heart Failure.  Soluble guanylate cyclase: a potential therapeutic target for heart failure.   Heart Fail Rev. 2013;18(2):123-134. doi:10.1007/s10741-012-9323-1PubMedGoogle ScholarCrossref
3.
Stasch  JP , Pacher  P , Evgenov  OV .  Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease.   Circulation. 2011;123(20):2263-2273. doi:10.1161/CIRCULATIONAHA.110.981738PubMedGoogle ScholarCrossref
4.
Pieske  B , Maggioni  AP , Lam  CSP ,  et al.  Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the Soluble Guanylate Cyclase Stimulator in Heart Failure Patients With Preserved EF (SOCRATES-PRESERVED) study.   Eur Heart J. 2017;38(15):1119-1127. doi:10.1093/eurheartj/ehw593PubMedGoogle ScholarCrossref
5.
Filippatos  G , Maggioni  AP , Lam  CSP ,  et al.  Patient-reported outcomes in the Soluble Guanylate Cyclase Stimulator in Heart Failure Patients With Preserved Ejection Fraction (SOCRATES-PRESERVED) study.   Eur J Heart Fail. 2017;19(6):782-791. doi:10.1002/ejhf.800PubMedGoogle ScholarCrossref
6.
Butler  J , Lam  CSP , Anstrom  KJ ,  et al.  Rationale and design of the VITALITY-HFpEF trial.   Circ Heart Fail. 2019;12(5):e005998. doi:10.1161/CIRCHEARTFAILURE.119.005998PubMedGoogle Scholar
7.
Green  CP , Porter  CB , Bresnahan  DR , Spertus  JA .  Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure.   J Am Coll Cardiol. 2000;35(5):1245-1255. doi:10.1016/S0735-1097(00)00531-3PubMedGoogle ScholarCrossref
8.
Flynn  KE , Piña  IL , Whellan  DJ ,  et al; HF-ACTION Investigators.  Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial.   JAMA. 2009;301(14):1451-1459. doi:10.1001/jama.2009.457PubMedGoogle ScholarCrossref
9.
O’Connor  CM , Whellan  DJ , Lee  KL ,  et al; HF-ACTION Investigators.  Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.   JAMA. 2009;301(14):1439-1450. doi:10.1001/jama.2009.454PubMedGoogle ScholarCrossref
10.
Little  R , Yau  L .  Intent-to-treat analysis for longitudinal studies with drop-outs.   Biometrics. 1996;52(4):1324-1333. doi:10.2307/2532847PubMedGoogle ScholarCrossref
11.
Ratitch  B , O’Kelly  M . Implementation of pattern-mixture models using standard SAS/STAT procedures. In: Proceedings of PharmaSUG2011 Conference. Paper SP04. Accessed May 13, 2020. https://www.pharmasug.org/proceedings/2011/SP/PharmaSUG-2011-SP04.pdf
12.
Armstrong  PW , Pieske  B , Anstrom  KJ ,  et al; VICTORIA Study Group.  Vericiguat in patients with heart failure and reduced ejection fraction.   N Engl J Med. 2020;382(20):1883-1893. doi:10.1056/NEJMoa1915928PubMedGoogle ScholarCrossref
13.
Redfield  MM , Anstrom  KJ , Levine  JA ,  et al; NHLBI Heart Failure Clinical Research Network.  Isosorbide mononitrate in heart failure with preserved ejection fraction.   N Engl J Med. 2015;373(24):2314-2324. doi:10.1056/NEJMoa1510774PubMedGoogle ScholarCrossref
14.
Borlaug  BA , Anstrom  KJ , Lewis  GD ,  et al; National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.  Effect of inorganic nitrite vs placebo on exercise capacity among patients with heart failure with preserved ejection fraction: the INDIE-HFpEF randomized clinical trial.   JAMA. 2018;320(17):1764-1773. doi:10.1001/jama.2018.14852PubMedGoogle ScholarCrossref
15.
Redfield  MM , Chen  HH , Borlaug  BA ,  et al; RELAX Trial.  Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.   JAMA. 2013;309(12):1268-1277. doi:10.1001/jama.2013.2024PubMedGoogle ScholarCrossref
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