Preemptive Pharmacogenetic-guided Metoprolol Management for PostoperativeAtrial Fibrillation in Cardiac Surgery

Study Overview
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Brief Summary
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Metoprolol is frequently administered to cardiac surgery patients to reduce the incidence of postoperative atrial fibrillation (PoAF). Metoprolol is metabolized by the enzyme CYP2D6, which is known to have many mutations that could influence a patient's ability to metabolize the drug. In this prospective clinical trial, the investigators will determine the genotype of CYP2D6 for patients undergoing cardiac surgery, provide an altered dosing recommendation for metoprolol, then report the relative effectiveness in managing PoAF for each pharmacogenetic- guided dosing category. The investigators will also explore the effects of personalized metoprolol dosing recommendations on outcomes in hospital length of stay, cost, and provider participation.

Official Title
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Preemptive Pharmacogenetic- Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The PREEMPTIVE- Pilot Trial

Conditions
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Post-operative Atrial Fibrillation

Intervention / Treatment
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* Other: Guided Metoprolol Management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years Scheduled for surgical procedure (coronary artery bypass graft and/or valve repair/replacement) at Vanderbilt University Medical Center Exclusion Criteria: History of allergic reactions or contraindications to beta-blockers Patients with persistent atrial fibrillation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacogenetic-guided metoprolol management<br> | Other: Guided Metoprolol Management<br>* CYP2D6 Genotyping: Consented patients will have blood drawn for genotyping prior to surgery. Patients will be classified as poor metabolizers, intermediate metabolizers, extensive (normal) metabolizers, or ultrafast metabolizers. Pharmacogenetic- Guided Metoprolol Management: A best practice advisory will be integrated into institutional clinical decision support systems for metoprolol dosing based on metabolic status of each patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of post-operative atrial fibrillation | Incidence of post-operative atrial fibrillation measured with post-operative electrocardiogram or rhythm strip, or at least two of the following: documentation in the progress notes, nursing notes, discharge summary, and change in medication. | From the end of anesthesia up to hospital discharge; usually 3-4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of genome tailored prescription changes | Rate of genome tailored prescription changes as measured by the proportion of patients in whom metoprolol prescription is based on CYP2D6 metabolizer status. | From the end of anesthesia up to hospital discharge; usually 3-4 days | 
| Length of hospital stay | Length of hospital stay (in days) after surgery | From end of surgery to hospital discharge; usually 3-4 days | 
| Overall cost of treatment |  | From end of surgery to hospital discharge; usually 3-4 days | 
| Cost of interventions to control or treat post-operative atrial fibrillation |  | From end of anesthesia to hospital discharge; usually 3-4 days | 
| Incidence of adverse drug events |  | From end of anesthesia to hospital discharge; usually 3-4 days | 
| Proportion of clinical decision support tool recommendations that were acknowledged and accepted by provider |  | From end of anesthesia to hospital discharge; usually 3-4 days | 
| Proportion of clinical decision support tool recommendations that were acknowledged but ignored by the provider. |  | From end of anesthesia to hospital discharge; usually 3-4 days | 
| Reasons for non-adherence to recommendations | Reasons for non-adherence to recommendations; prepopulated choices including 1. clinically inappropriate recommendation 2. provider preference 3. Other (free text option). | From end of anesthesia to hospital discharge; usually 3-4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metoprolol, CYP2D6, Genotype, Phenotype