Randomized Controlled Trial of Alert-Based Computerized Decision Support for Patients With Peripheral Artery Disease Not Prescribed Lipid-Lowering Therapy (PAD-ALERT)

This single-center, 400-patient, randomized controlled trial assesses the impact of a patient- and provider-facing EPIC Best Practice Advisory (BPA; alert-based computerized decision support tool) to increase guideline-directed utilization of statin and statin-alternative oral LDL-C lowering therapies in patients with PAD who are not being prescribed LDL-C-lowering therapy.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Vascular Diseases; Dyslipidemias; Peripheral Artery Disease
• Intervention / Treatment: Behavioral: Computer Alert

Detailed Description

A Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine recommends a low-density lipoprotein cholesterol (LDL-C) goal reduction of greater than 50% from baseline and a target of 55 mg/dL in patients with peripheral artery disease (PAD). An analysis of 1982 provider visits of patients with PAD in national outpatient databases in the U.S. between 2005-2012 showed that a statin was prescribed in only 33.1% of patients (Berger JS, Ladapo JA. J Am Coll Cardiol. 2017;69:2293-2300). Data from Europe demonstrates marginally better adherence to guidelines with 40% of patients with PAD prescribed a statin (Subherwal S, et al. Circulation. 2012;126:1345).

Explanations for underutilization of LDL-C-lowering therapy in patients with PAD include clinician knowledge gaps regarding evidence-based clinical practice guideline recommendations, provider inertia, the need for prior authorization for some agents, statin intolerance, and statin hesitancy. Statin intolerance is defined as the inability to tolerate a dose of statin required to sufficiently reduce cardiovascular risk and has been estimated to affect up to 15% of patients treated with statins (Banach M, et al. Arch Med Sci 2015;11:1-23 and Banach M, et al. Expert Opin Drug Saf 2015;14:935-55). While numerous statin options exist and non-statin oral options for LDL-C lowering, such as ezetimibe and bempedoic acid, are widely available, lack of awareness and inconsistent implementation contribute to underutilization in patients at high-risk for cardiovascular events, such as those with PAD. Bempedoic acid, with or without ezetimibe, is a newer option for LDL-C lowering that offers a lower prevalence of musculoskeletal side effects than statins (Diabetes Ther. 2021 Jul;12(7):1779-1789). However, familiarity with this option remains limited outside of Preventive Cardiology and Lipid Clinics.

The failure to achieve guideline-directed LDL-C targets due to clinician knowledge gaps, provider inertia, the need for prior authorization, statin intolerance, and statin hesitancy in the PAD population demonstrates similar clinical obstacles to other areas of cardiovascular medicine in which quality of care was impacted by provider and patient knowledge gaps. An alert-based computerized decision support (CDS) approach has been shown to be effective in such circumstances and could be similarly effective for optimizing lipid management in patients with PAD.

This single-center, 400-patient, randomized controlled trial assesses the impact of a patient- and provider-facing EPIC Best Practice Advisory (BPA; alert-based computerized decision support tool) to increase guideline-directed utilization of statin and statin-alternative oral LDL-C lowering therapies in patients with PAD who are not being prescribed LDL-C-lowering therapy.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gregory Piazza; Phone Number: 6177326984; Email: gpiazza@bwh.harvard.edu
• Study Contact Backup: Name: Candrika D Kharaini; Phone Number: 6177326984; Email: cdkhairani@@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Gregory Piazza, MD, MS; Phone Number: 617-732-6984; Email: gpiazza@bwh.harvard.edu
      • Contact: Email: gpiazza@bwh.harvard.edu
      • Principal Investigator: Gregory Piazza, MD, MS
      • Sub-Investigator: Samuel Goldhaber, MD
      • Sub-Investigator: Ron Blankstein, MD
      • Sub-Investigator: Jorge Plutzky, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients ≥ 18 years old
• Seen in Cardiovascular Medicine Clinic, Primary Care, Podiatry, Vascular Surgery, and Diabetology
• Medical history entry, visit diagnosis, or problem list entry of PAD
• Not prescribed LDL-C-lowering therapy

Exclusion Criteria:

• Patients taking a statin, ezetimibe, bempedoic acid, a PCSK9 inhibitor, inclisiran or a combination will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alert; Alert-based CDS will consist of an on-screen electronic alert that will notify the clinician that the patient has an indication for LDL-C-lowering therapy but is not prescribed any. The clinician will have the opportunity to proceed to an order template through which appropriate lipid-lowering can be prescribed. The clinician could also elect to learn more about current evidence-based recommendations for LDL-C lowering in the PAD population. Finally, the clinician could elect to proceed without ordering oral LDL-C-lowering therapy or reading evidence-based recommendations for LDL-C lowering but would have to provide a rationale for not doing so.	Behavioral: Computer Alert; On-screen alert-based decision support raising awareness of need for lipid-lowering therapy in patients with peripheral artery disease; Other Names: EPIC Best Practice Advisory
No Intervention: No Alert; No on-screen notification will be issued to the clinician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of prescription of oral LDL-C-lowering therapy	The frequency of prescription of oral LDL-C-lowering therapy will be assessed using a report from the medical record	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LDL-C level	Change in LDL-C level will be assessed via the medical record	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of all-cause mortality	The frequency will be assessed using a report from the medical record	6 months
Frequency of major adverse cardiovascular events	The frequency of major adverse cardiovascular events (including myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) will be assessed using a report from the medical record	6 months
Frequency of major adverse limb events	The frequency of major adverse limb events (including amputation and peripheral artery revascularization) will be assessed using a report from the medical record	6 months
Frequency of all-cause hospitalization	The frequency of all-cause hospitalization will be assessed using a report from the medical record	6 months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Esperion Therapeutics, Inc.
• Investigators: Principal Investigator: Gregory Piazza, BWH

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: March 3, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Dyslipidemia; Peripheral Vascular Disease; Peripheral Artery Disease; Computerized Decision Support
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Nutritional and Metabolic Diseases; Peripheral Arterial Disease; Dyslipidemias; Peripheral Vascular Diseases
• Other Study ID Numbers: 2022P002171

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Will consider IPD upon request.

Drug and device information, study documents

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