Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial

Figures

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  Fig. 1. CONSORT diagram. Flowchart illustrating study enrollment and randomization flowchart. EHR, electronic health record; ICD, implantable cardioverter defibrillator; MRI, magnetic resonance imaging.

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  Fig. 2. Clinical, patient-reported and hierarchical composite outcomes in the POLY-HF trial. a, Cumulative incidence of composite clinical HF events or death over 6 months of follow-up. The mean cumulative number of HF hospitalizations, ED visits or death per participant is shown, analyzed using the Andersen–Gill model for recurrent events. Numbers below the x axis indicate participants at risk at each timepoint. Adjusted HR, 0.41 (95% CI, 0.20–0.83); P = 0.013 (two-sided), with adjustment for age, sex, race, ethnicity, NYHA class, HF etiology, HF chronicity, eGFR and baseline NT-proBNP. b, KCCQ-OSS trajectories over 6 months by treatment group. Adjusted mean KCCQ-OSS scores with 95% CIs (dashed lines) at baseline and at 1, 3 and 6 months are shown, analyzed using linear mixed-effects models with maximum likelihood estimation. Higher scores indicate better health-related quality of life. Between-group comparison at 6 months: adjusted difference, 8.51 points (95% CI, 2.64–14.39); P = 0.005 (two-sided). c, Composite hierarchical endpoint calculated using the unmatched win ratio method with CIs derived from the log-transformed win ratio. The win ratio compares polypill versus enhanced usual…

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  Fig. 3. GDMT utilization and optimization over 6 months in the POLY-HF trial. a, Utilization of quadruple GDMT at any dose over 6 months by treatment group. The percentage of participants receiving all four GDMT classes (beta-blocker, RASi, MRA and SGLT2i) is shown at baseline and at 1, 3 and 6 months. Bars: proportion of participants receiving quadruple GDMT in each treatment arm; error bars: 95% CIs calculated using the Wilson score method. b, Utilization of optimal-dose quadruple GDMT over 6 months by treatment group. The percentage of participants receiving all four GDMT classes at optimal doses is shown, defined as ≥50% of target dose of beta-blocker and ACEi or ARB (or any dose of sacubitril/valsartan) and any dose of MRA and SGLT2i at baseline and at 1 month, 3 months and 6 months. Bars: proportion of participants receiving quadruple GDMT in each treatment arm; error bars: 95% CIs calculated using the Wilson score method. c, mHFC score over 6 months by treatment group. Mean mHFC scores are shown at baseline and at 1 month, 3 months and 6 months, with higher scores (range 0–100) indicating better medication optimization across the four GDMT components (beta-blocker, RASi, MRA and…

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  Extended Data Fig. 1. Individual-Level Changes in Left Ventricular Ejection Fraction From Baseline to 6 Months by Treatment Group. Individual-level changes in left ventricular ejection fraction (LVEF) by treatment arm. (A) Spaghetti plot depicting individual patient trajectories in LVEF (%) from baseline to 6 months for the Usual Care (red) and Polypill (blue) arms. (B) Waterfall plot of change in LVEF (ΔLVEF) from baseline to 6 months for each participant, ordered by magnitude of change and color-coded by treatment arm. The dashed line indicates the +15% super-responder threshold. Data are derived from n = 187 biologically independent participants with complete LVEF data at both baseline and 6 months (polypill, n = 93; enhanced usual care, n = 94).

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  Extended Data Fig. 2. Biomarker and Safety Laboratory Trajectories by Treatment Group. Longitudinal trajectories of (A) NT-proBNP (pg/mL), (B) log-transformed NT-proBNP, (C) serum creatinine (mg/dL), and (D) serum potassium (mEq/L) from baseline to 6 months in the polypill (blue) and enhanced usual care (red) groups. Points represent unadjusted mean values at each time point (baseline, 1 month, 3 months, and 6 months), and shaded bands represent 95% confidence intervals. Data are derived from n = 108 biologically independent participants in the polypill arm and n = 104 biologically independent participants in the enhanced usual care arm, with all available observations at each time point included in linear mixed-effects models with maximum likelihood estimation.

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  Extended Data Fig. 3. Self-Reported Medication Adherence by Treatment Group at Baseline and 6 Months. Distribution of self-reported medication adherence categories at baseline and 6 months in the enhanced usual care and polypill groups. Adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8), with scores categorized as high (score = 8), medium (score 6 to <8), or low (score <6). Stacked bars represent the proportion of participants in each adherence category at each time point. Data are derived from n = 108 biologically independent participants in the polypill arm and n = 104 biologically independent participants in the enhanced usual care arm at baseline; at 6 months, data were available for n = 95 in the polypill arm and n = 95 in the enhanced usual care arm.