Improving Implementation of Guideline-Recommended LDL-C Management in High-Risk Cardiovascular Patients

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in the United States. Although clinical guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) lowering for patients at high cardiovascular risk, many patients do not receive recommended LDL-C monitoring, lipid-lowering therapy (LLT) intensification, or achieve LDL-C treatment goals in routine clinical practice. This study is designed to evaluate the effectiveness and implementation of evidence-based strategies intended to improve guideline-recommended lipid management in high-risk cardiovascular patients.

This is a multicenter, hybrid Type II implementation-effectiveness study using a prospective stepped-wedge design with a retrospective comparator cohort. Participating cardiology practices will transition from pre-implementation standard care to implementation of one or more evidence-based strategies designed to improve LDL-C management. The study will evaluate both clinical effectiveness outcomes and implementation outcomes using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.

The study population includes adults with recent myocardial infarction (MI), coronary stent placement or a coronary artery calcium (CAC) score of 300 or greater who receive care at participating cardiovascular practices. A retrospective cohort meeting the same eligibility criteria will serve as the baseline comparator. The retrospective and prospective cohorts will be non-overlapping.

The study will be conducted in approximately five cardiovascular practice sites within the United States. During the retrospective phase, electronic health record (EHR) data and chart review will be used to evaluate historical LDL-C management and cardiovascular outcomes. These data will be used to generate clinician performance scorecards that provide feedback regarding adherence to guideline-recommended care.

All participating sites will implement clinician scorecards. Sites may additionally implement one or more evidence-based strategies, including:

* Passive electronic health record best practice alerts that notify clinicians about guideline-recommended LDL-C management.
* Physician education focused on contemporary cardiovascular risk reduction and guideline-directed lipid management.
* Patient education resources regarding LDL-C, cardiovascular risk, medication adherence, and lifestyle modification.
* An Advanced Practice Provider (APP) care pathway that provides additional patient follow-up, education, and care coordination.

Patients will receive routine clinical care according to local practice standards. Clinical data will be collected from the EHR at baseline and during follow-up. Prospective participants will be followed for up to 12 months after the index visit, with assessments performed at approximately 3, 6, and 12 months. Data collection may include lipid measurements, medication use, blood pressure, smoking status, cardiovascular events, healthcare utilization, and implementation-related measures.

The primary objective is to evaluate whether implementation of these evidence-based strategies improves LDL-C testing, LLT initiation or intensification, and achievement of guideline-recommended LDL-C goals at 6 months compared with the retrospective baseline cohort. Secondary objectives include assessing these outcomes at 3 and 12 months, evaluating additional cardiovascular risk factor management measures, and examining implementation outcomes including reach, acceptability, adoption, fidelity, and cost.

Implementation outcomes will be evaluated using quantitative and qualitative methods. Reach will assess the proportion and characteristics of patients receiving implementation strategies. Adoption will assess clinician utilization of the strategies. Acceptability will be evaluated through patient and clinician surveys. Implementation fidelity will be assessed through implementation logs documenting adaptations, barriers, and facilitators. Cost analyses will evaluate resources required to deploy the strategies across participating sites.

The study is expected to enroll up to approximately 500 patients per site, with an anticipated total enrollment of approximately 3,000 patients across five sites. Power analyses based on clustered regression models indicated that the planned sample size is sufficient to detect clinically meaningful improvements in LLT intensification and related outcomes while accounting for clustering by site and relevant patient-level covariates.

The retrospective cohort will serve as the baseline comparator for the prospective implementation cohort. Analyses will account for clustering of patients within participating sites and adjust for relevant patient characteristics, including demographics, comorbidities, baseline lipid levels, and medication use.

Primary effectiveness outcomes will be analyzed using mixed-effects regression and time-to-event methods. LLT initiation or intensification will be evaluated using mixed-effects logistic regression models. LDL-C testing and LDL-C goal attainment will be analyzed using time-to-event approaches, including Kaplan-Meier methods and Cox proportional hazards models.

Secondary outcomes, including smoking cessation, blood pressure goal attainment, use of glucose-lowering therapies among eligible patients, and implementation outcomes, will be assessed using appropriate mixed-effects, time-to-event, descriptive, and qualitative analytic methods. Implementation data will be analyzed according to the RE-AIM framework. Descriptive analyses will compare outcomes across sites and combinations of implementation strategies. Qualitative thematic analysis will be used to evaluate implementation experiences and barriers documented in implementation logs and other narrative data sources.

All analyses will be conducted on de-identified data, and study findings will be used to evaluate the effectiveness, feasibility, and potential scalability of multilevel implementation strategies intended to improve cardiovascular risk reduction and LDL-C management in high-risk cardiovascular populations.

Primary outcomes

• Binary indicator of LDL-C <55 mg/dL for patients with a recent MI or coronary stent and <70 mg/dL for patients undergoing PCI with no MI and/or ischemic heart disease or with a CAC score of at least 300 at 6-month post visit, with time to event. [Within 6-months post qualifying event.]: LDL-C level/goal attainment per guidelines. LDL-C laboratory testing.
• Binary indicator of patients who received LDL-C testing, with time to event. [Up to 365 days following qualifying event.]: LDL-C laboratory testing.
• Binary indicator of patients in whom lipid lowering therapy was initiated/intensified within the first six months after index event. [Within 6-months post qualifying event.]: Any change in prescriptions/dosages of lipid lowering medications (statins, ezetimibe, BAS, PCSK9 inhibitors, bempedoic acid +/- ezetimibe, fibrates, prescription OM3FA).

Secondary outcomes

• Persistence of cardiovascular risk goals after being discharged from the APP pathway strategy: Prescription of GLP1/SGLT2 inhibitors [Up to 365 days following qualifying event.]: Prescription or removal of GLP1/SGLT2 inhibitor medications.
• Persistence of cardiovascular risk after discharge from the APP pathway strategy: Cardiac Rehab [Up to 365 days following qualifying event.]: Binary indication of whether cardiac rehab was ordered and initiated.
• Persistence of cardiovascular risk after discharge from the APP pathway strategy: Blood Pressure [Up to 365 days following qualifying event.]: Self-reported home measurement or in-office measurement of blood pressure.
• Persistence of cardiovascular risk after discharge from the APP pathway strategy: BMI [Up to 365 days following qualifying event.]: Height in inches and weight in pounds as measured during office visit will be combined to report BMI in lbs/in\^2.
• Persistence of cardiovascular risk after discharge from the APP pathway strategy: Smoking Status [Up to 365 days following qualifying event.]: Binary indicator of smoking status.
• Binary indicator of LDL-C <55 mg/dL for patients with a recent MI or coronary stent and <70 mg/dL patients undergoing PCI with no MI and/or ischemic heart disease and for those with a CAC score > 300 at 3- and 12-month post visit, with time to event. [Up to 365 days following qualifying event.]: LDL-C laboratory testing, LDL-C level/goal attainment per guidelines.
• Binary indicator of patients in whom LLT was initiated/intensified at the 3- and 12-month visits post-index. [Up to 365 days following qualifying event.]: Any change in prescriptions/dosages of lipid lowering medications (statins, ezetimibe, BAS, PCSK9 inhibitors, bempedoic acid +/- ezetimibe, fibrates, prescription OM3FA).
• Binary indicator of patients with noted transition to non-smoking status, with time to event. [Up to 365 days following qualifying event.]: Subset of smokers at index event.
• Binary indicator of any prescribed GLP1 agonist or SGLT2 inhibitor within 3, 6, and 12-month follow-up periods post qualifying event. [Up to 365 days following qualifying event.]: Subset of diagnosed diabetics and pre-diabetics at index. Any changes in prescriptions/dosages of GLP1, SGLT2i medications.
• Percentage of patients who achieved their blood pressure goal. [Up to 365 days following qualifying event.]: Time to event analyses.
• Implementation outcome: Acceptability [From the implementation initiation through study completion, approximately 20 months.]: Patient and clinician ratings of acceptability of strategies measured via survey.
• Implementation Outcome: Reach [From the implementation initiation through study completion, approximately 20 months.]: Proportion of patients who received an implementation strategy, which strategy(ies), and their characteristics.
• Implementation Outcome: Adoption [From the implementation initiation through study completion, approximately 20 months.]: Proportion of clinicians who used a strategy and their characteristics.
• Implementation Outcome: Fidelity [From the implementation initiation through study completion, approximately 20 months.]: Adaptations to how strategies are implemented across healthcare sites (descriptive via logs).
• Implementation Outcome: Cost [From the implementation initiation through study completion, approximately 20 months.]: The cost of each strategy deployed at each site via a profit/loss statement.

Other outcomes

• Adverse clinical outcomes across follow-up (e.g., type of event, date of event) [Up to 365 days following qualifying event.]: Stroke, MI, PCI, CABG, hospitalization for UA, death (CV or any death)
• Adverse reactions to LLT (e.g., type of reaction, date of reaction) [Up to 365 days following qualifying event.]: EHR data on adverse reactions to LLTs.
• Reasons why LLT was not initiated/intensified per EHR notes from data pull/chart review. [Up to 365 days following qualifying event.]
• Whether measuring Lp(a) altered LLT intensification [Up to 365 days following qualifying event.]: Lp(a) laboratory testing
• Descriptive analysis comparing differences among sites implementing a strategy/combination of strategies and outcomes (LDL-C testing, LLT intensification, LDL-C goal attainment) [6- and 12-months post qualifying event.]: Number and type of strategies per site. Summary of primary outcomes per site.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients who were discharged from the hospital with a recent acute myocardial infarction (MI) (identified by catheterization records and with > 50% stenosis) or coronary stent (if they are very-high risk).
* Patients discharged from the hospital without a recent acute MI following Percutaneous Coronary Intervention (PCI) and/or with ischemic heart disease if they are high but not very high risk, or with a CAC score > 300 and aged 40-75.
* Patients aged 40-75 years old with CAC score > 300.

Exclusion Criteria:

\- Age under 18 years.