Polypill Strategy for the Evidence-Based Management of Heart Failure With Reduced Ejection Fraction in an Underserved Patient Population

Heart failure poses a major public health challenge in the United States. It affects more than 6.2 million people and is the leading cause of hospitalization among older adults, with a growing prevalence among Black, Hispanic, and low-income populations.

Despite advances in the treatment of heart failure, the associated morbidity and mortality remain high. From the time of heart failure diagnosis, survival is approximately 50% at 5-years and 10% at 10-years.8 Improved mortality and hospitalization rates have been observed due to the advent of mortality-reducing HFrEF therapies and earlier diagnosis. Nonetheless, substantial gaps in the uptake of guideline-directed medical therapies (GDMT) exist. GDMT, which include beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA), have been demonstrated to reduce all-cause mortality by > 50% when used in combination. Nonetheless, fewer than 25% of eligible patients currently receive these medications at any dose, with socially disadvantaged groups having the lowest rates of utilization.

The polypill is an alternative management strategy. The polypill combines multiple evidence-based medications in a single pill, which reduces pill burden and improves adherence. Therapy with multiple medications can be conveniently initiated at an early stage of disease, increasing the overall therapeutic benefit accrued over time. This is particularly relevant in settings where patients experience barriers to care due to high cost burden with copays associated with medication initiation, frequent lab tests, and need for multiple follow up visits.

Polypills have been shown to be feasible and effective in multiple settings, including in the prevention and treatment of cardiovascular disease (CVD). They have been well tolerated and additionally demonstrate significant improvements in adherence when compared to usual therapies in randomized control trials. However, no randomized trial to date has evaluated a polypill strategy for the treatment of heart failure, a condition in which pill burden and adherence pose substantial challenges to management.

The proposed study is a single-center, randomized trial to test the feasibility and effectiveness of a polypill-based strategy for the treatment of HFrEF (EF ≤40%) in a low-income population. The setting for our proposed study is Parkland Hospital in Dallas, Texas, a large county hospital that serves a racially diverse, uninsured population. We will utilize 4 distinct polypill formulations to allow for up-titration of the beta-blocker component of the polypill. The pill will contain spironolactone 12.5 mg, empagliflozin 10 mg, and 25 mg, 50 mg, 100 mg, or 150 mg of metoprolol succinate. The once-daily polypill will be added to baseline therapy with a renin-angiotensin system antagonist (ACEI, ARB, or ARNI).