Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial

Figures

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  Fig. 1. Kaplan-Meier curve for 180-day all-cause mortality in the overall study population

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  Fig. 2. a Forest plots of the treatment effect for 180-day all-cause mortality per clinical characteristic. Subgroups were defined by median (if continuous) or by category (if categorical). No significant interactions with treatment were observed for subgroups defined by clinical characteristics. Abbreviations: BMI, body mass index; LVEF, left ventricular ejection fraction; HFPEF, heart failure with preserved ejection fraction; COPD, chronic obstructive pulmonary disease; ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; MRA, mineralocorticoid receptor antagonist. b Forest plots of the treatment effect for 180-day all-cause mortality per biomarker level. Subgroups were defined by median. Forest plots demonstrated significant treatment interactions with ESAM (p = 0.045), GDF-15 (p = 0.035), neuropilin (p = 0.001), red blood cell count (p = 0.004), ST2 (p = 0.002), TNF-R1α (p = 0.028), and uric acid (p = 0.033). Abbreviations: ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; CRP, C-reactive protein; ESAM, endothelial cell selective adhesion molecule; GDF-15, growth differentation factor; LTBR, lymphotoxin beta receptor; NGAL, neutrophil…

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  Fig. 3. Subpopulation Treatment Effect Pattern Plot analysis of the treatment effects of rolofylline vs. placebo treatment effect measured by hazard ratio (<1 rolofylline better than placebo), with corresponding 95% confidence interval bands. y-axis: hazard ratio, x-axis: subpopulations by median. a TNF-R1α, tumor necrosis factor receptor 1 alpha levels (ng/mL) p value = 0.0128; b ST2 levels (ng/mL) p value = 0.0162; c neuropilin levels (ng/mL) p value = 0.0024. d WAP-4C, WAP four-disulfide core domain protein HE4 levels (ng/mL) p value = 0.002; e Total cholesterol (mmol/L) p value = 0.0192. f Potassium (mmol/L) p value = 0.0252

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  Fig. 4. a Kaplan-Meier survival curves according to points subgroup. Unadjusted Kaplan-Meier survival curves according to total points based on biomarker response score chart. Log rank ≤0.0001. b Unadjusted Kaplan-Meier estimates of survival in patients with four points, according to treatment group. Log rank = 0.0178. c Unadjusted Kaplan-Meier estimates of survival in patients with three points, according to treatment group. Log rank = 0.638. d Unadjusted Kaplan-Meier estimates of survival in patients with two points, according to treatment group. Log rank = 0.247. e Unadjusted Kaplan-Meier estimates of survival in patients with one point, according to treatment. Log rank = 0.304. f Unadjusted Kaplan-Meier estimates of survival in patients with zero points, according to treatment. Log rank = 0.0015