Dr Ambarish Pandey:

Hello, my name is Dr Ambarish Pandey. I'm a Cardiologist and Associate Professor of Internal Medicine at UT Southwestern Medical Center in Dallas, Texas.

What gaps in heart failure management does the polypill strategy address?

Heart failure with reduced ejection fraction is common among older adults and is associated with a high burden of morbidity and mortality.

Management of heart failure relies upon taking guideline-recommended medical therapies that have been approved and have been shown to improve cardiovascular outcomes. However, there is a big implementation gap in uptake of these therapies, such that only 15% of patients who are eligible are on all the four pillars of therapy that are recommended by current guidelines.

Also, a lot of these patients have high burden of polypharmacy, so the adherence to these medications is low. We wanted to address this challenge of low uptake of guideline-recommended medical therapy and poor adherence to these medications among those who are prescribed by taking this novel approach of a polypill-based management of patients with heart failure with reduced ejection fraction.

What was the trial design and patient population?

So this was a randomised controlled trial, open label at two centers. We enrolled 212 participants who were patients with heart failure with reduced ejection fraction, with the ejection fraction less than 40%. Patients were randomised on a 1:1 fashion to a polypill that contained three of the four guideline-recommended medical therapies, which include metoprolol in a titratable formulation from 25 to 150, spironolactone, as well as an SGLT2 inhibitor, empagliflozin.

The usual care participants got their medications in a usual fashion, one pill, separate pills for each class of drug. And the primary outcome of the study was change in LV ejection fraction as assisted by cardiac MRI from baseline to 6-month follow up.

Our secondary outcomes of interest were quality of life, heart failure hospitalisation or ED visits, and a composite hierarchical endpoint assessed by a win ratio that included hospitalisation, mortality, quality of life, as well as adherence assessed by therapeutic drug monitoring and measuring serum blood levels of these drugs.

And we also looked at other outcomes of how well patients accepted and how well patients were taking these medicines in an implementation science fashion.

What were the key findings revealed at AHA 25?

So we observed that in our trial, at the end of six-month follow up, patients who were randomised to the polypill arm had higher left ventricular ejection fraction than those who were in the usual care arm, and then the absolute difference in ejection fraction was 3.4%.

And we also observed that patients in the polypill arm had a much less burden of readmission or heart failure related ED visits, and that risk was lowered by 60%. Patients in the polypill arm also had 10 points greater quality of life score as assessed by the Kansas City Cardiomyopathy Questionnaire.

And we also found that patients in the polypill arm had much greater adherence to the polypill medication than the usual care arm, as assisted by measuring serum drug levels in these patients.

What are the practical implications of these findings?

I think our study has important clinical implications.

The burden of non adherence, the burden of lack of uptake of evidence-based therapies in heart failure with reduced ejection fraction is high, and that is associated with worse outcomes. Our study findings identify a novel approach to managing these patients, whereby we can provide them a polypill that can reduce the pill burden and help better uptitrate these medications and improve adherence and lead to better clinical outcomes.

We need future studies that can actually test how to implement it, how to scale it up. Our polypill was a very unique intervention where we encapsulated the approved available therapies using a pharmacy. So it did not require recompounding, it just required encapsulation.

So we believe this is a scalable model that can be done in any pharmacy that has encapsulation abilities, and this needs to be tested in different implementation settings to identify the best approach to scale it up.