Elsevier

Journal of Cardiac Failure

Volume 27, Issue 9, September 2021, Pages 949-956
Journal of Cardiac Failure

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial

https://doi.org/10.1016/j.cardfail.2021.05.016Get rights and content

Highlights

  • The recent VICTORIA trial included 5050 patients with heart failure with reduced ejection fraction and a recent worsening heart failure event.

  • We analyzed the 2524 placebo patients in the trial to identify clinical variables associated with risk of clinical outcomes.

  • Independent predictors of increased clinical events included longer duration of heart failure, worse symptom class, prior myocardial infarction and laboratory values including the heart failure marker brain natriuretic peptide, liver tests, and chloride and uric acid levels.

ABSTRACT

Background

The prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction included high-risk patients with HF with reduced ejection fraction and a recent worsening HF event. The study participants had a high event rate despite the use of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group.

Methods and Results

Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association functional class II–IV) and an ejection fraction of less than 45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical end points, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, and nonlinearities. Optimism-corrected c-indices were calculated using 200 bootstrap samples. Over a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 patients (38.5%). Independent predictors of increased risk for the primary end point included HF characteristics (longer HF duration and worse New York Heart Association functional class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death.

Conclusions

Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data—including novel measures—performed well in high-risk patients with HF who were receiving excellent guideline-based clinical care.Clinical Trial Registration: Clinicaltrials.gov identifier, NCT02861534.Lay Summary: Patients with heart failure may benefit from tools that help clinicians to better understand a patient's risk for future events like hospitalization. Relatively few risk models have been created after the worsening of heart failure in a contemporary cohort. We provide insights on the risk factors for clinical events from a recent, large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.

Section snippets

Patient Cohort and Trial Overview

The VICTORIA trial design, baseline characteristics, and outcomes have been previously reported elsewhere.5,7,8 Briefly, VICTORIA was a multicenter, international, randomized, placebo-controlled trial that investigated the efficacy and safety of the soluble guanylate cyclase stimulator, vericiguat, on a background of evidence-based medical and device therapy in 5050 patients with chronic HFrEF (New York Heart Association [NYHA] functional class II–IV) and a recent worsening HF event. Eligible

Results

Table 1 presents the baseline characteristics of the study population. The median age of participants was 68 years, 23.9% were female, and 64.1% were White. The majority of patients were in NYHA functional classification II (59.3%) or III (39.4%) at the time of randomization with a median N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) of 2821 pg/mL. Supplemental Table 2 presents the numbers missing for the different variables with most variables having less than 2% missing data.

Discussion

The VICTORIA model identifies key prognostic variables for the high-risk cohort of patients with HFrEF with recent clinical worsening. These variables include many of those that are routinely known or collected at the time of HF hospitalization or outpatient worsening. Specifically, the clinical characteristics with independent prognostic usefulness for the primary end point of HF hospitalization or cardiovascular death included HF characteristics (longer HF duration and worse NYHA functional

Conclusions

Predictive models developed in a large diverse clinical trial with extensive clinical and laboratory data—including novel measures—performed well in high-risk patients with HF who were receiving excellent guideline-based clinical care. These models refining patient prognosis may further guide clinical decision-making and future clinical trial design.

Disclosures

The VICTORIA trial was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Bayer.

Dr Mentz reports research support and honoraria from Bayer and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Hillary Mulder has nothing to report. Dr Mosterd has nothing to report. Dr Sweitzer reports consulting fees from Merck. Dr. Senni has nothing to report. Dr Butler reports consulting fees from Bayer, Merck, Amgen, AstraZeneca,

Funding

The VICTORIA trial was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Bayer AG, Wuppertal, Germany.

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