Polypill improves LVEF and increases GDMT use in HFrEF

AHA 2025 – In POLY-HF among HFrEF patients with low socioeconomic status, the use of a GDMT polypill improved clinical outcomes, quality of life, medication adherence, and GDMT utilization compared with enhanced usual care.

This summary is based on the presentation of Ambarish Pandey, MD (Dallas, TX, USA) at the AHA Scientific Sessions 2025 - A Polypill Strategy for Heart Failure with Reduced Ejection Fraction: The POLY-HF Trial.

Introduction and methods

Only 15% of patients with HFrEF are treated with all 4 GDMT classes, suggesting polypharmacy is a problem for this population. Although polypills combining multiple medications have proven effective for the treatment of other CVD, it is a challenge to fit the individualized medication doses required for HF therapy into a one-size-fits-all pill.

The POLY-HF (Polypill Strategy for Heart Failure With Reduced Ejection Fraction) trial was a pragmatic, open-label, phase 2 RCT conducted at 2 hospitals in Dallas, TX, USA. In this trial, 212 patients with HFrEF (LVEF ≤40%) not receiving target GDMT doses were randomized to either the use of an over-encapsulated polypill (consisting of metoprolol succinate, empagliflozin, and spironolactone) once daily plus individual ARNI prescription or enhanced usual care (i.e., GDMT initiation and uptitration). The ARNI was not included in the polypill as this was a twice-daily medication. Of the study population, >80% were of self-reported Black race or Hispanic ethnicity and ~70% were uninsured or received county-sponsored health insurance coverage.

The primary endpoint was the change in LVEF as measured by cardiac MR from baseline to 6 months. Secondary endpoints included quality of life as measured with the KCCQ – Overall Summary Score (OSS), HF hospitalizations, emergency department visits, and all-cause mortality.

Main results

• At baseline, 44% of the patients randomized to the polypill (n=108) were on quadruple GDMT at any dose, compared with 52% of the patients assigned to enhanced usual care (n=104).
• During follow-up, LVEF (confirmed by both cardiac MR and ultrasound) improved in both treatment groups, with a greater increase in the polypill group: LVEF increased from 29.7% at baseline to 39.9% at 6 months in the polypill group and from 28.9% to 36.5% enhanced usual-care group (between-group difference at 6 months: 3.4 percentage points; P=0.024).
• The cumulative number of HF hospitalizations, emergency department visits, or mortality was 60% lower in the polypill group than the enhanced usual-care group by 7 months (P<0.05).
• At 6 months, the KCCQ-OSS was 71.8 in the polypill group versus 63.3 in the control group (difference: 8.5; 95%CI: 2.64–14.39; P=0.005), which is a clinically meaningful difference in quality of life.
• GDMT use at optimal doses was higher in the polypill group than the control group at 6 months (71% vs. 42%; P<0.05). A gradual increase in GDMT use at optimal doses was observed over time, with significant between-group differences also at 1 and 3 months (both P<0.05).
• Medication adherence based on serum levels of metoprolol and spironolactone was 79.3% in the polypill group and 54.3% in the control group (P<0.05).

Conclusion

The POLY-HF trial among HFrEF patients with low socioeconomic status showed the use of a GDMT polypill increased LVEF at 6 months, reduced the occurrence of HF events or mortality, and improved quality of life, medication adherence, and GDMT utilization, compared with enhanced usual care.

- Our reporting is based on the information provided at the AHA Scientific Sessions 2025 -