Adherence to Dyslipidemia Therapy: Harnessing Evidence From Randomized Evaluations in AtheroSclerotic CardioVascular Disease (ADHERE-ASCVD)

Adherence to Dyslipidemia Therapy: Harnessing Evidence From Randomized Evaluations in AtheroSclerotic CardioVascular Disease (ADHERE-ASCVD)

The goal of the ADHERE-ASCVD study is to evaluate and optimize patient-facing messaging strategies to improve statin refill and adherence among adults with atherosclerotic cardiovascular disease (ASCVD) or diabetes.

The main questions it aims to answer are:

1. Do different outreach methods (such as text messages, secure portal messages, or email) increase short-term statin refill compared to usual care?
2. Among patients who do not initially refill their prescription, does changing the outreach method improve refill rates?

The team with operational partners will evaluate the comparitive effectivessness of multiple messaging strategies delivered through existing health system communication channels, including SMS (text messaging), secure patient portal messages, non-secure email, and usual care (no additional outreach).

Participants

• Receive an initial outreach message encouraging statin refill (or usual care) Be monitored for statin refill within 14 days
• Potentially receive a second outreach message using the same or a different communication method if they do not initially refill their prescription
• Have their medication refill patterns tracked over time, including longer-term adherence outcomes

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes; ASCVD
• Intervention / Treatment: Behavioral: SMS (Initial Outreach); Behavioral: SMS (Follow-up for Non-responders); Behavioral: Secure Portal Message (Follow-up for Non-responders); Behavioral: Non-secure Email (Follow-up for Non-responders); Behavioral: Secure Portal Message (Initial Outreach); Behavioral: Non-secure Email (Initial Outreach)

Detailed Description

Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death worldwide. Statins can reduce ASCVD events by 25%, yet nearly half of high-risk adults remain untreated, and adherence is poor. Since statin adherence impacts quality metrics like Medicare Stars ratings, even small gains in refill rates can boost health plan performance. However, no data driven approaches exist to optimize statin adherence.

The ADHERE-ASCVD study is a pragmatic, Prospective Randomized Open-label Blinded End-point (PROBE) randomized clinical trial designed to evaluate and optimize patient-facing messaging strategies to improve statin refill and adherence. The project leverages a two-stage Sequential Multiple Assignment Randomized Trial (SMART) design to evaluate both initial outreach strategies and adaptive follow-up approaches among patients with suboptimal statin adherence.

In the first stage, eligible participants will be randomized to one of four outreach strategies: secure portal message, SMS (text message), non-secure email, or usual care (no proactive outreach). The primary response window is 14 days following message delivery, during which statin refill will be ascertained using pharmacy dispensing records. Participants who refill within this window will be classified as responders and will not receive further study intervention.

Participants who do not refill within 14 days will be classified as non-responders and re-randomized in a second stage to receive one of three follow-up strategies: (1) continued outreach using the same communication modality ("stay"), (2) outreach using an alternative modality ("switch"), or (3) usual care with no additional outreach. For the initial implementation phase, message content will remain consistent across stages within each modality, and the intervention focuses on evaluating modality and sequencing rather than content optimization.

The primary estimands correspond to (1) first-stage effects comparing outreach modalities, (2) conditional second-stage effects among non-responders comparing stay, switch, and usual care strategies, and (3) dynamic treatment regime (DTR) effects comparing embedded adaptive sequences of interventions. DTR effects will be estimated using inverse-probability-weighted estimators that account for sequential randomization.

In addition to estimating average treatment effects, the study will develop predictive models to characterize treatment effect heterogeneity across patient subgroups. The modeling framework focuses on estimating differences in response across messaging strategies conditional on baseline patient characteristics. Model evaluation will emphasize calibration of predicted treatment contrasts and the identification of clinically meaningful differences between strategies that can inform targeted outreach.

This study is designed to generate actionable evidence within a learning health system by identifying optimal messaging strategies and sequences for improving statin refill and adherence, and enabling future deployment of targeted, data-driven outreach approaches.

• Study Type: Interventional
• Enrollment (Estimated): 22000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ankeet S Bhatt, MD, MBA, ScM; Phone Number: 415-407-1754; Email: Ankeet.S.Bhatt@kp.org
• Study Contact Backup: Name: Mirasol M Apostol-Largeteau, MPH; Phone Number: 415-407-1754; Email: Mirasol.M.Apostol-Largeteau@kp.org

Study Locations

• United States
  • California
    • Pleasant Hill, California, United States, 94588
      • Kaiser Permenante Northern California
      • Contact: Ankeet Bhatt, MD, MBA, ScM; Phone Number: 4154706571; Email: ankeet.s.bhatt@kp.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥18 years
2. Active Kaiser Permanente Northern California (KPNC) membership
3. Diagnosis of atherosclerotic cardiovascular disease (ASCVD) or diabetes and inclusion in the Preventing Heart Attacks and Strokes Everyday (PHASE) Registry
4. No statin prescription fill within the prior 3 months
5. Statin adherence <80% in the prior 12 months
6. Active kp.org account within the past 12 months
7. Valid email address and text-capable phone number on file

Exclusion Criteria

1. Documented allergic reaction or contraindication to statin therapy
2. Receiving hospice care
3. Medicare beneficiaries
4. Other exclusions applied per operational standard practice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SMS/SMS; Participants in this arm will receive an initial SMS (text message) encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a second SMS.	Behavioral: SMS (Initial Outreach); Participants will receive an initial SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.; Behavioral: SMS (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.
Experimental: SMS/Secure Portal Message; Participants in this arm will receive an initial SMS (text message) encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a secure portal message.	Behavioral: SMS (Initial Outreach); Participants will receive an initial SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.; Behavioral: Secure Portal Message (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up secure portal message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.
Experimental: SMS/Non-secure Email; Participants in this arm will receive an initial SMS (text message) encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a non-secure email.	Behavioral: SMS (Initial Outreach); Participants will receive an initial SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.; Behavioral: Non-secure Email (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.
Experimental: SMS/Usual Care; Participants in this arm will receive an initial SMS (text message) encouraging statin refill. Participants who do not refill their prescription within 14 days will receive no additional outreach (usual care).	Behavioral: SMS (Initial Outreach); Participants will receive an initial SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.
Experimental: Secure Portal Message/Secure Portal Message; Participants in this arm will receive an initial secure portal message encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a second secure portal message.	Behavioral: Secure Portal Message (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up secure portal message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.; Behavioral: Secure Portal Message (Initial Outreach); Participants will receive an initial secure message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.
Experimental: Secure Portal Message/SMS; Participants in this arm will receive an initial secure portal message encouraging statin refill. Participants who do not refill their prescription within 14 days will receive an SMS (text message).	Behavioral: SMS (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.; Behavioral: Secure Portal Message (Initial Outreach); Participants will receive an initial secure message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.
Experimental: Secure Portal Message/Non-secure Email; Participants in this arm will receive an initial secure portal message encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a non-secure email.	Behavioral: Non-secure Email (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.; Behavioral: Secure Portal Message (Initial Outreach); Participants will receive an initial secure message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.
Experimental: Secure Portal Message/Usual Care; Participants in this arm will receive an initial secure portal message encouraging statin refill. Participants who do not refill their prescription within 14 days will receive no additional outreach (usual care).	Behavioral: Secure Portal Message (Initial Outreach); Participants will receive an initial secure message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.
Experimental: Non-secure Email/Non-secure Email; Participants in this arm will receive an initial non-secure email encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a second non-secure email.	Behavioral: Non-secure Email (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.; Behavioral: Non-secure Email (Initial Outreach); Participants will receive an initial non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.
Experimental: Non-secure Email/SMS; Participants in this arm will receive an initial non-secure email encouraging statin refill. Participants who do not refill their prescription within 14 days will receive an SMS (text message).	Behavioral: SMS (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up SMS (text message) encouraging statin refill. Messages may include reminder prompts and interactive features implemented through automated keyword-triggered responses that provide refill instructions or educational information.; Behavioral: Non-secure Email (Initial Outreach); Participants will receive an initial non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.
Experimental: Non-secure Email/Secure Portal Message; Participants in this arm will receive an initial non-secure email encouraging statin refill. Participants who do not refill their prescription within 14 days will receive a secure portal message.	Behavioral: Secure Portal Message (Follow-up for Non-responders); Participants who do not refill their prescription within 14 days of the initial outreach will receive a follow-up secure portal message through the kp.org patient portal encouraging statin refill. Messages are delivered within the secure portal environment and may include informational and reminder content.; Behavioral: Non-secure Email (Initial Outreach); Participants will receive an initial non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.
Experimental: Non-secure Email/Usual Care; Participants in this arm will receive an initial non-secure email encouraging statin refill. Participants who do not refill their prescription within 14 days will receive no additional outreach (usual care).	Behavioral: Non-secure Email (Initial Outreach); Participants will receive an initial non-secure email encouraging statin refill. Emails may include informational content and reminders but are delivered outside of the secure patient portal.
No Intervention: Usual Care/Usual Care; Participants in this arm will receive usual care with no proactive outreach during the study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Statin refill after message delivery	Proportion of participants who refill a statin prescription following message delivery (first-stage intervention) or, among non-responders, following second-stage messaging. Refill status will be determined using pharmacy dispensing records.	Within 14 days after each stage of message delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to statin refill	Time from message delivery (first-stage or second-stage, as applicable) to statin refill, measured using pharmacy dispensing records. Participants who do not refill will be censored at disenrollment, death, or end	Up to 30 days after each stage of message delivery
Statin refill	Proportion of participants who refill a statin prescription following message delivery (first-stage or second-stage, as applicable), based on pharmacy dispensing records.	Within 30 days after message delivery
Statin persistence	Proportion of participants who remain persistent with statin therapy, defined as continuous statin use without a gap exceeding 60 days between prescription fills.	At 6 months and 12 months post randomization.
Statin adherence (proportion of days covered)	Adherence to statin therapy measured as the proportion of days covered (PDC), defined as the number of days with statin supply available divided by the number of days in the observation period. Adherence will be assessed as both a continuous measure and as a binary indicator using a threshold of ≥80%.	At 6 months and 12 months post randomization.

Collaborators and Investigators

• Sponsor: Kaiser Permanente

Study record dates

Study Major Dates

• Study Start (Estimated): April 14, 2026
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: statin; ASCVD; statin therapy; SMART design; patient outreach; ASCVD management; messaging strategies
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Enzymes; Enzymes and Coenzymes; Transferases; Alkyl and Aryl Transferases; Spermine Synthase
• Other Study ID Numbers: ADHERE-ASCVD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No