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

@article{pandey2026polypill,
  title = {{Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial}},
  author = {Ambarish Pandey and Neil Keshvani and Syed K. Rizvi and Fatemeh Khashami and Katarina Yaros and Muhammad Usman and Matthew W. Segar and Anand K. Jain and Juan David Coellar and Myriam Bustillo-Rubio and Zachary L. Cox and Jennifer T. Thibodeau and Chul Ahn and Deepak K. Gupta and Alvin Chandra and Mark H. Drazner and M. Tarique Hussain and Vlad Gabriel Zaha and Thomas J. Wang},
  journal = {Nature Medicine},
  year = {2026},
  month = jul,
  doi = {10.1038/s41591-026-04504-5},
  url = {https://doi.org/10.1038/s41591-026-04504-5},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial
AU  - Ambarish Pandey
AU  - Neil Keshvani
AU  - Syed K. Rizvi
AU  - Fatemeh Khashami
AU  - Katarina Yaros
AU  - Muhammad Usman
AU  - Matthew W. Segar
AU  - Anand K. Jain
AU  - Juan David Coellar
AU  - Myriam Bustillo-Rubio
AU  - Zachary L. Cox
AU  - Jennifer T. Thibodeau
AU  - Chul Ahn
AU  - Deepak K. Gupta
AU  - Alvin Chandra
AU  - Mark H. Drazner
AU  - M. Tarique Hussain
AU  - Vlad Gabriel Zaha
AU  - Thomas J. Wang
PY  - 2026
DA  - 2026/07/02
JO  - Nature Medicine
DO  - 10.1038/s41591-026-04504-5
UR  - https://doi.org/10.1038/s41591-026-04504-5
AB  - Heart failure with reduced ejection fraction carries a poor prognosis. Although guideline-directed medical therapy reduces morbidity and mortality, its real-world utilization is low. Accordingly, we conducted an open-label randomized trial (POLY-HF) at two centers enrolling a predominantly underserved population to test whether a polypill strategy improves cardiac function in heart failure. Adults with heart failure and left ventricular ejection fraction ≤40% were randomized to a once-daily polypill containing metoprolol succinate (25/50/100/150 mg), spironolactone 12.5 mg and empagliflozin 10 mg, or rapid uptitration of individual guideline-directed medical therapy medications ('enhanced usual care'). Participants also continued treatment with a renin-angiotensin system inhibitor or sacubitril/valsartan as a separate pill. The primary endpoint was ejection fraction as assessed by cardiac magnetic resonance imaging at 6 months. Secondary endpoints included clinical outcomes and adherence. We randomized 212 patients (median age 54 years, 22% female, 54% Black). Follow-up magnetic resonance imaging data were available for 187 (88%) participants who were included in the modified intention-to-treat analysis. Polypill treatment was associated with greater improvement in ejection fraction compared to enhanced usual care (between-group difference, 3.3 percentage points, 95% confidence interval, 0.2-6.4; P = 0.039), meeting the primary outcome. Individuals randomized to the polypill also had a 60% lower rate of heart failure hospitalizations or emergency department visits (adjusted rate ratio, 0.40; 95% confidence interval, 0.18-0.88; P = 0.024). Adherence, assessed by blood concentrations of metoprolol and spironolactone, was higher with polypill treatment than with enhanced usual care (79% versus 54%, P = 0.001). The polypill was well tolerated, with fewer adverse events with polypill treatment as compared to enhanced usual care. A polypill for heart failure was associated with a significant improvement in cardiac function as compared with enhanced usual care. ClinicalTrials.gov registration: NCT04633005 .
SN  - 1078-8956
SN  - 1546-170X
SN  - 1744-7933
ER  -