Should Polypills Be Used for Heart Failure With Reduced Ejection Fraction?

Ambarish Pandey, MD, MSCS; Neil Keshvani, MD; Thomas J. Wang, MD


Circulation. 2022;146(4):276-278. 

In This Article

Abstract and Introduction


Heart failure (HF) is the leading cause of hospitalization among older adults and a major cause of morbidity and mortality. Use of guideline-directed medical therapies (GDMT), including β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, can substantially reduce heart failure–related morbidity and all-cause mortality.[1] Accordingly, practice guidelines from all major societies recommend early initiation of multiple classes of GDMT.

Nonetheless, <25% of patients are prescribed a renin-angiotensin receptor antagonist, β-blocker, and mineralocorticoid receptor antagonist in combination, and <1% receive at least 4 medications (including sodium-glucose cotransporter-2 inhibitors) at target doses.[2] Black individuals and individuals of lower socioeconomic status are least likely to receive GDMT, exacerbating disparities in HF outcomes. For instance, in the CHAMP-HF registry (Change the Management of Patients With Heart Failure), 50% to 90% of Black patients received no GDMT or less than half the target doses.[2] Fewer than 15% underwent initiation and titration over 12 months. Likewise, low rates of GDMT are observed among individuals with total household incomes <$50 000.

Addressing gaps in the use of GDMT has substantial potential to produce short- and long-term measurable benefits. In the IMPROVE HF registry (Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting), programs aimed at improving GDMT use resulted in a mean increase in left ventricular ejection fraction from 26% to 32% in 2 years, with one-third of patients observing a 10% increase in left ventricular ejection fraction. Furthermore, observations from the SCD-HeFT trial (Sudden Cardiac Death in Heart Failure) demonstrated early improvements in left ventricular ejection fraction recorded within 3 to 7 months of treatment initiation in 67% of patients treated with β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. These changes have been subsequently associated with lower mortality rates and rehospitalization for HF. Both underprescribing and low rates of adherence contribute to gaps in HF with reduced ejection fraction (HFrEF) care, driven by complex medication regimens, high out-of-pocket costs, and large pill burdens. Interventions aimed at improving the use of GDMT with improved care integration, patient education, and self-management tools have had limited success.[1] Another approach is clearly needed.