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Guideline-directed medical therapies (GDMT) for patients living with heart failure with reduced ejection fraction (HFrEF), used in combination at recommended doses, result in significant improvements in cardiac function, quality of life, and survival. However, busy clinicians treating stable patients with chronic diseases often "leave well enough alone". This clinical inertia results in GDMT underuse and a missed opportunity to achieve attainable health goals. The EPIC-HF trial tested effects of patient activation through a brief video and 1-page checklist sent to patients just prior to a clinic visit; the PROMPT-HF trial tested tailored alerts delivered to clinicians during clinic visits. Both electronic health record tools increased the appropriate use of GDMT while taking into consideration patients' preferences and overall medical care. Yet, neither EPIC-HF nor PROMPT-HF were implemented widely. The I-I-CAPTAIN-HF study—Implementation and Interaction of Clinician And Patient-facing Tools Aiming to Intensify Neurohormonal medicines for Heart Failure with reduced ejection fraction—will implement and test the EPIC-HF and PROMPT-HF tools at 5 diverse health systems across the United States in a type-2 hybrid implementation-effectiveness, cluster randomized trial. Funded by the Patient-Centered Outcomes Research Institute, the 5-year study started in March 2024. Aim 1 will modify and implement the EPIC-HF and PROMPT-HF tools at 5 health systems through participatory work with a multi-level team. The Practical, Robust Implementation and Sustainability Model (PRISM) will guide the delivery of implementation strategies that respect mandatory aspects of the interventions and explore helpful adaptations. Prototypes of interoperable, next-generation, "plug-and-play" versions of the tools will leverage advanced interoperability standards such as the Health Level Seven International (HL7) SMART-on-FHIR and CDS Hooks standards. Aim 2 will test the effectiveness and the interaction of the EPIC-HF and PROMPT-HF tools to improve GDMT prescribing from before to after clinic visits using a 2 × 2 factorial design randomized at the clinician-level. About 200 clinicians and 2000 patients will be enrolled to either usual care, EPIC-HF, PROMPT-HF, or both. Aim 3 will evaluate ongoing implementation of both tools to promote broad dissemination. Formal evaluation using PRISM will include patient and clinician surveys and interviews to understand optimal intervention design and delivery, as well as adaptations to contextual factors, that will lead to broad, effective, and sustained use of these clinical tools to improve GDMT use. We anticipate the lessons learned from I-I-CAPTAIN-HF about how to best use the EPIC-HF and PROMPT-HF tools will improve patient-clinician interactions, address therapeutic inertia, and enhance patient-centered prescribing for the growing number of people living with HFrEF. [ABSTRACT FROM AUTHOR]