About

Dr. Caitrin W McDonough is an assistant professor in the Department of Pharmacotherapy and Translational Research at the University of Florida College of Pharmacy. She holds a B.S. in Biochemistry with a minor in chemistry from the University of Iowa, a Ph.D. in Molecular Medicine and Translational Science from Wake Forest University School of Medicine, and an M.S. in Biomedical Informatics from the University of Florida. Her postdoctoral fellowship was completed at the University of Florida in Cardiovascular Pharmacogenomics under the guidance of Dr. Julie Johnson. Her research focuses on identifying and predicting patients at high risk for cardiovascular disease. She employs multiple methods, including regression modeling and machine learning, to analyze data from various sources such as electronic health records, insurance claims, and ‘omics data. Her work aims to identify factors or signatures associated with adverse cardiovascular outcomes and drug response. Dr. McDonough is involved in NIH-funded projects utilizing data from the All of Us research program to study treatment-resistant hypertension, adverse cardiovascular outcomes after P2Y12 inhibitor treatment, and adverse outcomes with statin therapy. She is also a co-leader of the International Consortium for Antihypertensive Pharmacogenomic Studies, collaborating globally to advance the field of antihypertensive pharmacogenomics.

Research topics

• Medicine
• Internal medicine
• Biology
• Genetics
• Cardiology
• Bioinformatics
• Immunology

Selected publications

• Impact of Area-Level Socioeconomic Deprivation on Post-PCI Outcomes Stratified by P2Y12 Inhibitor Therapy

  JACC Advances · 2026-02-03

  articleOpen access

  BACKGROUND: Social deprivation influences postpercutaneous coronary intervention (PCI) outcomes, but whether it affects outcomes by antiplatelet therapy is unknown. OBJECTIVES: inhibitors following PCI was assessed. METHODS: inhibitor across 3 institutions. Social Deprivation Index (SDI) and Social Vulnerability Metric (SVM) were assigned using zip code tabulation areas. Multivariable Cox regression was used to evaluate the association between SDI and SVM (per unit increase) and risk for major atherothrombotic events (MAE) (death, myocardial infarction, stent thrombosis, ischemic stroke, or revascularization for unstable angina) and bleeding (Global Use of Strategies to Open Occluded Coronary Arteries Moderate-Severe) with clopidogrel and alternative therapy (eg, prasugrel or ticagrelor). RESULTS: Overall, 3,141 patients (mean age: 63 years; 33% female; 68% with acute coronary syndrome) were included. In clopidogrel-treated patients (n = 1,852), SDI was associated with higher risk for MAE (adjusted HR: 1.009; 95% CI: 1.001-1.016; P = 0.018) but not bleeding (adjusted HR: 1.001; 95% CI: 0.990-1.012; P = 0.838). In patients on alternative therapy (n = 1,289), SDI was associated with a higher risk for bleeding (adjusted HR: 1.014; 95% CI: 1.001-1.028; P = 0.048), but not MAE (adjusted HR: 0.998; 95% CI: 0.988-1.007; P = 0.652). SVM was not significantly associated with adverse outcomes with clopidogrel or alternative therapy after adjustment. CONCLUSIONS: inhibitor-related outcomes remains to be determined.

  PublisherDOI

• Impact of Area-Level Socioeconomic Deprivation on Post-PCI Outcomes Stratified by P2Y12 Inhibitor Therapy

  UNC Libraries · 2026-02-13

  articleOpen access
  PublisherDOI

• Impact of Area-Level Socioeconomic Deprivation on Post-PCI Outcomes Stratified by P2Y12 Inhibitor Therapy

  Open MIND · 2026-01-01

  article

• Evaluating the Evidence for <scp>CYP2C19</scp> Inhibitor Classifications: A Scoping Review

  Clinical Pharmacology & Therapeutics · 2025-05-20 · 4 citations

  review

  The Food and Drug Administration (FDA) Table of Inhibitors and the Flockhart Table™ are important references for identifying CYP2C19 inhibitors. Accurate inhibitor classification is essential for evaluating phenoconversion and managing drug-drug interactions. The objective of this study was to assess the concordance between inhibitor classifications according to the FDA and Flockhart tables and pharmacokinetic data from the primary literature. A scoping review of PubMed, product labels, and the Drug Interactions Database (DIDB®) up to April 2024 was conducted. Inhibitor-substrate pairs (e.g., fluoxetine-omeprazole) were assigned literature-reported classifications (i.e., weak, moderate, or strong) based on pharmacokinetic data. Concordance between literature-reported and listed classifications was evaluated. Of 90 inhibitor-substrate pairs identified, 66% involved sensitive substrates, which were the focus of our primary analysis. Among sensitive inhibitor-substrate pairs, 36% of FDA-listed and 45% of Flockhart-listed classifications were concordant with the literature. CYP2C19 phenotype appeared to impact concordance, with greater concordance among normal metabolizers for both FDA-listed (42%) and Flockhart-listed (50%) classifications. Steady state status and dosing also appeared to affect concordance. Discrepancies between listed and literature-reported classifications led to the following recommendations: (1) upgrade fluoxetine from moderate to strong in the Flockhart Table™, (2) upgrade fluconazole from moderate to strong in the Flockhart Table™, (3) downgrade omeprazole (and esomeprazole) from moderate to weak in the Flockhart Table™, and (4) include footnotes describing dose-dependent inhibition for fluvoxamine and fluconazole in both tables. These recommendations aim to improve the accuracy of CYP2C19 inhibitor classifications and the clinical utility of these tables.

  PublisherDOI

• Abstract 4364354: <i>CYP2C19-</i> Guided Therapy Antiplatelet Therapy Influences Outcomes After Percutaneous Coronary Intervention in Black Patients

  Circulation · 2025-11-03

  article

  Introduction: Cytochrome P450 2C19 ( CYP2C19 ) loss-of-function (LOF) genotypes reduce clopidogrel, but not prasugrel or ticagrelor, effectiveness following percutaneous coronary intervention (PCI). Accumulating evidence has demonstrated the clinical benefit of using CYP2C19 genotype to guide selection of P2Y12 inhibitor therapy after PCI. However, these studies have primarily included patients of European and East Asian ancestry. Therefore, there is a paucity of data on the impact of CYP2C19 -guided antiplatelet therapy on clinical outcomes in Black patients. Aim: We aimed to assess the impact of CYP2C19 -guided P2Y12 inhibitor selection on risk for major atherothrombotic events (MAE) among self-reported Black patients within one-year post-PCI. Methods: Black adults across five institutions who underwent PCI and clinical CYP2C19 genotyping for LOF alleles and were prescribed clopidogrel or an alternative P2Y12 inhibitor (prasugrel, ticagrelor) were included. The ultimate prescribing decision was at the prescriber’s discretion. Atherothrombotic events were manually abstracted from the electronic health record and adjudicated. The primary outcome, MAE (composite of all-cause mortality, myocardial infarction, ischemic stroke, stent thrombosis, or unstable angina requiring revascularization), was compared between patients treated with alternative P2Y12 inhibitors (irrespective of CYP2C19 status) versus LOF allele carriers treated with clopidogrel, and separately versus non-LOF carriers treated with clopidogrel, using multivariable Cox regression. Results: The study population consisted of 1,244 Black patients (mean age 61±12 years; 44% women; 70% with acute coronary syndrome), with 734 patients prescribed clopidogrel (170 LOF-carriers, 564 non-LOF-carriers) and 510 prescribed an alternative inhibitor. MAE rates were higher in the LOF-clopidogrel vs alternative inhibitor group (29.1 vs . 13.9 events per 100 PY; unadjusted HR: 0.49 [95%CI: 0.31-0.77], p=&lt;0.01; adjusted HR: 0.54 [95%CI: 0.32-0.91], p=0.02). MAE rates did not differ between the non-LOF-clopidogrel and alternative inhibitor groups (15.4 vs. 13.9 events per 100PY; unadjusted HR: 0.99 [95% CI:0.61-1.32], p=0.57; adjusted HR: 0.99 [95% CI:0.65-1.50], p=0.97). Conclusion: These data suggest that clopidogrel is as effective as alternative P2Y12 inhibitors in post-PCI Black patients without a CYP2C19 LOF allele, while alternative therapy improves outcomes in LOF allele carriers.

  PublisherDOI

• Evaluation of Potential Racial Disparities in CYP2C19‐Guided P2Y12 Inhibitor Prescribing After Percutaneous Coronary Intervention

  UNC Libraries · 2025-05-01

  articleOpen access

  Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared P2Y₁₂ inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI. Patients from 9 sites that performed clinical CYP2C19 genotyping after PCI were included. Alternative therapy (e.g., prasugrel or ticagrelor) was recommended for CYP2C19 no-function allele carriers, in whom clopidogrel is predicted to be less effective. The primary outcome was choice of P2Y₁₂ inhibitor (clopidogrel vs. alternative therapy) based on genotype. Of 3,342 patients included, 2,448 (73%) were White, and 659 (20%) were Black. More Black than White patients had a no-function allele (34.3% vs. 29.7%, P&nbsp;=&thinsp;0.024). At hospital discharge following PCI, 44.2% of Black and 44.0% of White no-function allele carriers were prescribed alternative therapy. At the time of the last follow-up within 12&thinsp;months, numerically fewer Black (51.8%) than White (56.7%) no-function allele carriers were prescribed alternative therapy (P&nbsp;=&nbsp;0.190). However, the difference was not significant after accounting for other factors associated with P2Y₁₂ inhibitor selection (odds ratio 0.79, 95% confidence interval 0.58-1.08). Alternative therapy use did not differ between Black (14.3%) and White (16.7%) patients without a no-function allele (P&nbsp;=&nbsp;0.232). Among real-world patients who received CYP2C19 testing after PCI, P2Y₁₂ inhibitor prescribing rates did not differ between Black and White patients. Our data suggest an absence of racial disparity in genotype-guided antiplatelet prescribing among patients receiving CYP2C19 testing.

  PublisherDOI

• Characterizing Alzheimer’s Disease and Related Dementia in a Hypertension Population Within the State of Florida Using Electronic Health Record–Based Data

  Clinical Pharmacology & Therapeutics · 2025-12-08 · 1 citations

  articleOpen accessSenior authorCorresponding

  Hypertension is a known modifiable risk factor for Alzheimer's disease and related dementia (ADRD). However, it is unknown how variance in hypertension control, antihypertensive medications, and social determinants of health, such as social deprivation index (SDI), influence the risk of developing ADRD. Validated hypertension computable phenotype algorithms were applied to electronic health record data from the OneFlorida Data Trust (1/1/2013-12/31/2016), to identify apparent treatment-resistant hypertension (aTRH), and hypertension-control levels (well-controlled hypertension, intermediate-controlled hypertension, uncontrolled hypertension). The primary outcome was a new ADRD diagnosis using validated ICD-9/10 codes. Multiple adjusted stepwise logistic regression models were used to identify factors associated with ADRD development. ADRD cumulative hazard incidence per hypertension control levels was assessed using the Nelson-Aalen estimator and log-rank test. A total of 57,273 hypertension patients with 6401 (11%) incident ADRD cases were included in the analysis. The average age was 67 years, with 57% females and 32% identifying as Black or African American. aTRH was a significant ADRD predictor (OR: 1.327, 95% CI: 1.234-1.427), compared to other hypertension phenotypes. aTRH was also significantly associated with a higher incidence of ADRD over time (P < 0.0001). Patients prescribed thiazide diuretics (OR: 0.894, 95% CI: 0.837-0.956) and fixed-dose combination medications (OR: 0.804, 95% CI: 0.732-0.882) had a lower risk of ADRD. A linear relationship between SDI quartiles and ADRD risk was found. aTRH was significantly associated with the development of ADRD. Our study also highlights the importance of comprehensive hypertension control and socioeconomic interventions in preventing or reducing ADRD risk in hypertension patients.

  PublisherOA PDFDOI

• <i>CYP2D6</i> Phenotypes and Emergency Department Visits Among Patients Receiving Opioid Treatment

  JAMA Network Open · 2025-07-28 · 4 citations

  articleOpen access

  Importance: Cytochrome P450 2D6 (CYP2D6) bioactivates hydrocodone, tramadol, codeine, and oxycodone to active metabolites that primarily provide analgesic activity. Reduced CYP2D6 activity may be associated with poor pain control. Objective: To evaluate associations of impaired CYP2D6 activity based on genotype or CYP2D6 inhibitors, alone and together, with analgesic activity of CYP2D6-metabolized opioids among patients with pain. Design, Setting, and Participants: This retrospective national, community-based cohort study used electronic health records and genetics data from the All of Us Research Program. Participants included adults prescribed at least 1 CYP2D6-metabolized opioid for more than 7 days between January 1, 2014, and December 31, 2022, with whole-genome sequencing data available. Analysis groups were defined by CYP2D6 phenotype, which was determined based on CYP2D6 genotype or CYP2D6 inhibitor-mediated phenoconversion. Statistical analysis was performed from July 1, 2023, to January 15, 2025. Exposures: CYP2D6-metabolized opioids, with or without concomitant CYP2D6 inhibitor exposure, based on prescription records and overlap with opioids. Main Outcomes and Measures: The primary outcome was occurrence of any pain-related emergency department (ED) visits during opioid treatment, up to 60 days after opioid initiation. The association between ED visits and CYP2D6 phenotype was assessed using inverse probability treatment weighting-adjusted logistic regression. Additional analyses were conducted by drug and isolating CYP2D6 genotype and inhibitors. Results: Among 31 669 patients (mean [SD] age, 51.2 [15.4] years; 66.5% women) prescribed CYP2D6-metabolized opioids, 15 960 had reduced CYP2D6 activity, and 15 709 had normal or high CYP2D6 activity based on genotype and inhibitors. A higher percentage of patients with reduced CYP2D6 activity (hereafter referred to as phenotypic intermediate metabolizers [pIMs] or phenotypic poor metabolizers [pPMs]) had experienced pain-related ED visits compared with patients with normal or high CYP2D6 activity (phenotypic normal metabolizers [pNMs] and phenotypic ultrarapid metabolizers [pUMs]) (2.1% vs 1.8%; inverse probability-weighted odds ratio, 1.19; 95% CI, 1.06-1.33). There were no significant differences in ED visits among CYP2D6 genotypic IMs or PMs vs NMs or UMs when testing all 4 drugs together. Among genotypic NMs, ED visits were more frequent among the individuals prescribed CYP2D6 inhibitors (inverse probability-weighted odds ratio, 1.49; 95% CI, 1.32-1.68). In analyses by medication, drug interactions were important for all 4 medications, while genotype associations were significant only for hydrocodone, tramadol, and codeine. Conclusions and Relevance: In this cohort study, reduced CYP2D6 activity was associated with increased ED visits among individuals treated with CYP2D6-metabolized opioids. This finding suggests that incorporating data on CYP2D6 genotype and accounting for drug interactions in opioid prescribing may improve pain management and reduce ED visits.

  PublisherOA PDFDOI

• Use of<scp>CYP2D6</scp>Inhibitors with<scp>CYP2D6</scp>Opioids: Association with Emergency Department Visits for Pain

  Clinical Pharmacology & Therapeutics · 2024-05-26 · 9 citations

  articleOpen access

  Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6-dependent opioids while on CYP2D6-inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6-dependent opioids utilizing electronic health records data from the University of Florida Health (2015-2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine-treated patients exposed to CYP2D6-inhibitor antidepressants (n = 7,043) had a higher crude rate of pain-related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6-inhibitor antidepressant-exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27-2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control.

  PublisherOA PDFDOI

• Characterizing apparent treatment resistant hypertension in the United States: insights from the <i>All of Us</i> Research Program

  Journal of the American Medical Informatics Association · 2024-08-24 · 5 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND: Hypertension (HTN) remains a significant public health concern and the primary modifiable risk factor for cardiovascular disease, which is the leading cause of death in the United States. We applied our validated HTN computable phenotypes within the All of Us Research Program to uncover prevalence and characteristics of HTN and apparent treatment-resistant hypertension (aTRH) in United States. METHODS: Within the All of Us Researcher Workbench, we built a retrospective cohort (January 1, 2008-July 1, 2023), identifying all adults with available age data, at least one blood pressure (BP) measurement, prescribed at least one antihypertensive medication, and with at least one SNOMED "Essential hypertension" diagnosis code. RESULTS: We identified 99 461 participants with HTN who met the eligibility criteria. Following the application of our computable phenotypes, an overall population of 81 462 were further categorized to aTRH (14.4%), stable-controlled HTN (SCH) (39.5%), and Other HTN (46.1%). Compared to participants with SCH, participants with aTRH were older, more likely to be of Black or African American race, had higher levels of social deprivation, and a heightened prevalence of comorbidities such as hyperlipidemia and diabetes. Heart failure, chronic kidney disease, and diabetes were the comorbidities most strongly associated with aTRH. β-blockers were the most prescribed antihypertensive medication. At index date, the overall BP control rate was 62%. DISCUSSION AND CONCLUSION: All of Us provides a unique opportunity to characterize HTN in the United States. Consistent findings from this study with our prior research highlight the interoperability of our computable phenotypes.

  PublisherOA PDFDOI

Recent grants

• Hypertension Prediction and Identification in All of Us

  NIH · $305k · 2023–2025

• INTEGRATIVE DATA APPROACHES FOR RESISTANT HYPERTENSION IDENTIFICATION AND PREDICTION

  NIH · $486k · 2018–2022

• NIH Grant F31MH069136

  NIH · $63k · 2006

Frequent coauthors

• Julie A. Johnson

  University of North Carolina at Chapel Hill

  335 shared

• Yan Gong

  University of Florida

  316 shared

• Rhonda M. Cooper‐DeHoff

  University of Florida

  270 shared

• John G. Gums

  University of Florida

  232 shared

• Eric Boerwinkle

  The University of Texas Health Science Center at Houston

  225 shared

• Stephen T. Turner

  Australian Regenerative Medicine Institute

  213 shared

• Amber L. Beitelshees

  University of Maryland, Baltimore

  166 shared

• Kent R. Bailey

  Mayo Clinic

  141 shared

Education

• B.S., Biochemistry (with a minor in chemistry)

  University of Iowa

• Ph.D., Molecular Medicine and Translational Science

  Wake Forest University School of Medicine