Case study: De-risking clinical development and driving therapeutic innovation in heart failure

Despite advances in guideline-directed medical therapy, heart failure (HF) readmission rates have worsened over the past decade. Optimizing acute inpatient decongestion is critical in mitigating HF morbidity and mortality, but few new treatment strategies have emerged in recent years. Loop diuretics remain the cornerstone of treatment, requiring careful and frequent dosing adjustments to remove fluid without overtaxing the kidneys – a challenging balance to strike.

Challenges in evolving treatments for heart failure

The lack of treatment evolution for HF is partly due to the difficulty and cost of studying complex inpatient interventions in depth. The best source of real-world data (RWD) on patients with HF, the Acute Decompensated Heart Failure National Registry (ADHERE), is nearly 20 years old. Creating ADHERE took four years and tens of millions of dollars, making regular updates or replication challenging.

Since ADHERE, researchers have used clinical trials and registries to study decongestion outcomes, but these sources have limitations.

TREAT-AHF identifies need for safer and more effective treatments

Reprieve Cardiovascular enlisted researchers from organizations including Stanford University, Kaiser Permanente San Francisco Medical Center, and Vanderbilt University Medical Center to study contemporary HF decongestion strategies and identify clinical predictors of weight loss in HF hospitalizations in the US.

Using Truveta Data, comprised of complete EHR data – including notes and images – linked with SDOH, mortality, and claims data, they developed the TREAT-AHF (Trajectory and Response to Emergently Administered Therapy for Acute Heart Failure) registry, describing baseline variables associated and benchmarking against ADHERE and GWTG-HF (Get With The Guidelines Heart Failure).

The researchers were able to study more than 165,000 ADHF patient journeys – which is approximately three times the number of patients in the ADHERE registry – to understand real-world outcomes and patient care trends. In addition, they also analyzed more than 10,000 ADHF patients as a concurrent real-world control in conjunction with Pilot RCT.

Overall, the findings suggest that contemporary decongestion during acute HF hospitalization remains suboptimal, indicating a need for safer and more effective diuretic strategies. The analysis found that changes in body weight, a common marker for clinical decongestion, have not significantly changed in the past 20 years.

TREAT-AHF patients had higher frequencies of cardiovascular comorbidities, facility disposition, and inotrope use, suggesting a potentially higher-risk population than prior registry analyses. As a result, inpatient mortality and median length of stay observed in TREAT-AHF were higher than those seen in ADHERE and GWTG-HF.

There was also a significant uptake in use of novel therapies, including ARNi and SGLT2i, during the study period. These therapies were not reflected in older registry data, which could impact efforts to ensure patient safety during clinical trials.

The power of RWD from EHRs in elevating research and patient care

The analysis required deep clinical context at the patient level (e.g., lab values, inpatient medication administrations, biometric, procedural, comorbidity, and length of stay data), nationally representative data, sufficient scale, and a dynamic analytics platform – highlighting the power of complete, clean, and timely EHR data.?The findings also showcase the potential for real-world evidence to prompt changes in HF treatment decisions and clinical guidelines.

For the full findings and insight into what made the study possible, download the case study.