Adherence Through Digital Health: Evaluating Randomized Engagement in Heart Failure

Heart failure is a common chronic condition associated with hospitalization, impaired quality of life, and premature death. Guideline-directed medical therapy (GDMT) can reduce the risk of cardiovascular death and worsening heart failure, but patients must continue to refill and take these medications to receive their full benefit. Medication nonadherence remains common and contributes to a gap between the benefits observed in clinical trials and those achieved in routine care. The ADHERE-HF study is a pragmatic, prospective, open-label, patient-level randomized clinical trial designed to evaluate whether digital outreach improves refill of overdue GDMT medications among adults with heart failure. The study will compare a text-first digital outreach strategy with usual care and will be conducted through existing health system pharmacy operations.

Eligible participants will be randomized in a 1:1 ratio to digital outreach or usual care. Randomization will be stratified by ejection fraction category and by whether the participant has opted in to pharmacy text outreach at the time of randomization. Participants assigned to digital outreach who have opted in to pharmacy text messaging will receive interactive two-way text messages. These messages notify participants that they may be due for a medication refill, allow them to verify their identity, and provide options to request mail-order delivery or pharmacy pickup. Participants may also report that they do not intend to refill or request assistance. Responses indicating medication, cost, dosing, or other concerns may be referred to pharmacy staff for follow-up. Participants assigned to digital outreach who have not opted in to pharmacy text messaging will receive an interactive automated telephone call. The call allows participants to verify their identity and select among refill options using the telephone keypad. Participants may request refill at their usual pharmacy, use or establish mail-order delivery, or transfer to a pharmacy representative for assistance. Participants assigned to usual care will receive no additional study-specific outreach. They will continue to receive routine pharmacy refill communications and other standard health system services. Participants will remain assigned to their randomized strategy for 12 months. If any eligible GDMT medication becomes overdue during follow-up, participants in the digital outreach group may receive another outreach contact. Outreach modality will be based on the participant's pharmacy text opt-in status at the time of each contact.

The primary outcome is refill of at least one GDMT medication that was overdue at randomization within 14 days of the outreach date. Secondary outcomes include refill within 28 days, the proportion of overdue medications refilled, time to first refill, mail-order fulfillment, medication adherence and persistence at 6 and 12 months, heart failure hospitalization, and all-cause mortality. All outcomes will be obtained from routinely collected pharmacy dispensing, electronic health record, administrative, and digital communication data.

The study has no study-specific visits or direct participant contact by the investigative team. This study is designed to generate actionable evidence within a learning health system by determining whether scalable digital outreach improves refill and adherence to guideline-directed heart failure medications and whether the strategy should be implemented more broadly.