Publications by authors named "Rhonda M Cooper-DeHoff"

186 Publications

Tracking Blood Pressure Control Performance and Process Metrics in 25 US Health Systems: The PCORnet Blood Pressure Control Laboratory.

J Am Heart Assoc 2021 11 6;10(21):e022224. Epub 2021 Oct 6.

University of California San Francisco San Francisco CA.

Background The National Patient-Centered Clinical Research Network Blood Pressure Control Laboratory Surveillance System was established to identify opportunities for blood pressure (BP) control improvement and to provide a mechanism for tracking improvement longitudinally. Methods and Results We conducted a serial cross-sectional study with queries against standardized electronic health record data in the National Patient-Centered Clinical Research Network (PCORnet) common data model returned by 25 participating US health systems. Queries produced BP control metrics for adults with well-documented hypertension and a recent encounter at the health system for a series of 1-year measurement periods for each quarter of available data from January 2017 to March 2020. Aggregate weighted results are presented overall and by race and ethnicity. The most recent measurement period includes data from 1 737 995 patients, and 11 956 509 patient-years were included in the trend analysis. Overall, 15% were Black, 52% women, and 28% had diabetes. BP control (<140/90 mm Hg) was observed in 62% (range, 44%-74%) but varied by race and ethnicity, with the lowest BP control among Black patients at 57% (odds ratio, 0.79; 95% CI, 0.66-0.94). A new class of antihypertensive medication (medication intensification) was prescribed in just 12% (range, 0.6%-25%) of patient visits where BP was uncontrolled. However, when medication intensification occurred, there was a large decrease in systolic BP (≈15 mm Hg; range, 5-18 mm Hg). Conclusions Major opportunities exist for improving BP control and reducing disparities, especially through consistent medication intensification when BP is uncontrolled. These data demonstrate substantial room for improvement and opportunities to close health equity gaps.
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http://dx.doi.org/10.1161/JAHA.121.022224DOI Listing
November 2021

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients.

Metabolites 2021 Sep 21;11(9). Epub 2021 Sep 21.

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.

Plasma renin activity (PRA) is a predictive biomarker of blood pressure (BP) response to antihypertensives in European-American hypertensive patients. We aimed to identify the metabolic signatures of baseline PRA and the linkages with BP response to β-blockers and thiazides. Using data from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) trial, multivariable linear regression adjusting for age, sex and baseline systolic-BP (SBP) was performed on European-American individuals treated with metoprolol ( = 198) and chlorthalidone ( = 181), to test associations between 856 metabolites and baseline PRA. Metabolites with a false discovery rate (FDR) < 0.05 or < 0.01 were tested for replication in 463 European-American individuals treated with atenolol or hydrochlorothiazide. Replicated metabolites were then tested for validation based on the directionality of association with BP response. Sixty-three metabolites were associated with baseline PRA, of which nine, including six lipids, were replicated. Of those replicated, two metabolites associated with higher baseline PRA were validated: caprate was associated with greater metoprolol SBP response (β = -1.7 ± 0.6, = 0.006) and sphingosine-1-phosphate was associated with reduced hydrochlorothiazide SBP response (β = 7.6 ± 2.8, = 0.007). These metabolites are clustered with metabolites involved in sphingolipid, phospholipid, and purine metabolic pathways. The identified metabolic signatures provide insights into the mechanisms underlying BP response.
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http://dx.doi.org/10.3390/metabo11090645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466669PMC
September 2021

Potential of Minocycline for Treatment of Resistant Hypertension.

Am J Cardiol 2021 10 1;156:147-149. Epub 2021 Aug 1.

Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida.

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http://dx.doi.org/10.1016/j.amjcard.2021.07.004DOI Listing
October 2021

Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies.

Clin Pharmacol Ther 2021 09 15;110(3):723-732. Epub 2021 Aug 15.

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (β-blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide-like diuretics, n = 3,516; ACE-inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115). One signal reached genome-wide significance in the β-blocker-SNP interaction analysis (rs139945292, Interaction P = 1.56 × 10 ). rs139945292 was validated through BP response to β-blockers, with the T-allele associated with less BP reduction (systolic BP response P = 6 × 10 , Beta = 3.09, diastolic BP response P = 5 × 10 , Beta = 1.53). The T-allele was also associated with increased adverse cardiovascular risk within the β-blocker treated patients' subgroup (P = 2.35 × 10 , odds ratio = 1.57, 95% confidence interval = 1.23-1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in β-blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50 kb upstream gene NTM (neurotrimin). No SNPs attained genome-wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE-inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in β-blocker treated patients. Further investigation into this region is warranted.
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http://dx.doi.org/10.1002/cpt.2355DOI Listing
September 2021

Multi-Institutional Implementation of Clinical Decision Support for and Genotyping in Antihypertensive Management.

J Pers Med 2021 May 27;11(6). Epub 2021 May 27.

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

(1) Background: Clinical decision support (CDS) is a vitally important adjunct to the implementation of pharmacogenomic-guided prescribing in clinical practice. A novel CDS was sought for the , , and genes to guide optimal selection of antihypertensive medications among the African American population cared for at multiple participating institutions in a clinical trial. (2) Methods: The CDS committee, made up of clinical content and CDS experts, developed a framework and contributed to the creation of the CDS using the following guiding principles: 1. medical algorithm consensus; 2. actionability; 3. context-sensitive triggers; 4. workflow integration; 5. feasibility; 6. interpretability; 7. portability; and 8. discrete reporting of lab results. (3) Results: Utilizing the principle of discrete patient laboratory and vital information, a novel CDS for , , and was created for use in a multi-institutional trial based on a medical algorithm consensus. The alerts are actionable and easily interpretable, clearly displaying the purpose and recommendations with pertinent laboratory results, vitals and links to ordersets with suggested antihypertensive dosages. Alerts were either triggered immediately once a provider starts to order relevant antihypertensive agents or strategically placed in workflow-appropriate general CDS sections in the electronic health record (EHR). Detailed implementation instructions were shared across institutions to achieve maximum portability. (4) Conclusions: Using sound principles, the created genetic algorithms were applied across multiple institutions. The framework outlined in this study should apply to other disease-gene and pharmacogenomic projects employing CDS.
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http://dx.doi.org/10.3390/jpm11060480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226809PMC
May 2021

New Drugs Approved in 2020.

Am J Med 2021 09 30;134(9):1096-1100. Epub 2021 Apr 30.

Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville. Electronic address:

In 2020, the US Food and Drug Administration approved 53 novel drugs. Thirty-six of the 53 (68%) drugs were reviewed and approved through an expedited review pathway, and 31 of the 53 (58%) were approved for treatment of a rare disease. This review includes a summary of the novel drugs approved by the US Food and Drug Administration in 2020.
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http://dx.doi.org/10.1016/j.amjmed.2021.03.034DOI Listing
September 2021

Association of 1-Year Blood Pressure Variability With Long-term Mortality Among Adults With Coronary Artery Disease: A Post Hoc Analysis of a Randomized Clinical Trial.

JAMA Netw Open 2021 04 1;4(4):e218418. Epub 2021 Apr 1.

Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville.

Importance: Accumulating evidence indicates that higher blood pressure (BP) variability from one physician office visit to the next (hereafter referred to as visit-to-visit BP variability) is associated with poor outcomes. Short-term measurement (throughout 1 year) of visit-to-visit BP variability in high-risk older patients may help identify patients at increased risk of death.

Objective: To evaluate whether short-term visit-to-visit BP variability is associated with increased long-term mortality risk.

Design, Setting, And Participants: The US cohort of the International Verapamil SR-Trandolapril Study (INVEST), a randomized clinical trial of 16 688 patients aged 50 years or older with hypertension and coronary artery disease, was conducted between September 2, 1997, and December 15, 2000, with in-trial follow-up through February 14, 2003. The study evaluated a calcium antagonist (sustained-release verapamil plus trandolapril) vs β-blocker (atenolol plus hydrochlorothiazide) treatment strategy. Blood pressure measurement visits were scheduled every 6 weeks for the first 6 months and biannually thereafter. Statistical analysis was performed from September 2, 1997, to May 1, 2014.

Exposures: Visit-to-visit systolic BP (SBP) and diastolic BP variability during the first year of enrollment using 4 different BP variability measures: standard deviation, coefficient of variation, average real variability, and variability independent of the mean.

Main Outcomes And Measures: All-cause death, assessed via the US National Death Index, beginning after the exposure assessment period through May 1, 2014.

Results: For the present post hoc analysis, long-term mortality data were available on 16 688 patients (9001 women [54%]; mean [SD] age, 66.5 [9.9] years; 45% White patients, 16% Black patients, and 37% Hispanic patients). During a mean (SD) follow-up of 10.9 (4.2) years, 5058 patients (30%) died. All 4 variability measures for SBP were significantly associated with long-term mortality after adjustment for baseline demographic characteristics and comorbidities. After comparison of lowest vs highest variability measure quintiles, the magnitude of the association with death remained statistically significant even after adjustment for baseline demographic characteristics and comorbidities (average real variability: adjusted hazard ratio [aHR], 1.18; 95% CI, 1.08-1.30; standard deviation: aHR, 1.14; 95% CI, 1.04-1.24; coefficient of variation: aHR, 1.15; 95% CI, 1.06-1.26; variability independent of the mean: aHR, 1.15; 95% CI, 1.05-1.25). The signal was stronger in women compared with men. Associations of diastolic BP variability measures with death were weaker than for SBP and were not significant after adjustment.

Conclusions And Relevance: This study suggests that, in a large population of older patients with hypertension and coronary artery disease, short-term visit-to-visit SBP variability was associated with excess long-term mortality, especially for women. Efforts to identify and minimize visit-to-visit SBP variability may be important in reducing excess mortality later in life.

Trial Registration: ClinicalTrials.gov Identifier: NCT00133692.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085725PMC
April 2021

Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

PLoS One 2021 23;16(4):e0248080. Epub 2021 Apr 23.

Department of Population Health Sciences, Division of Health System Innovation and Research, University of Utah School of Medicine, Salt Lake City, UT, United States of America.

Background: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses.

Methods And Findings: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days).

Conclusions: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248080PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064574PMC
May 2021

Optimal systolic blood pressure and reduced long-term mortality in older hypertensive women with prior coronary events - An analysis from INVEST☆.

Int J Cardiol Hypertens 2020 Dec 16;7:100052. Epub 2020 Sep 16.

Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.

Background: Hypertension and coronary artery disease (CAD) are a prevalent combination in older women, however limited data are available to guide blood pressure (BP) management. We hypothesized that older women with hypertension and CAD may not derive long-term benefit by achieving systolic BP (SBP) < 130 mmHg.

Methods: We analyzed long-term all-cause mortality data from the International Verapamil SR/Trandolapril Study (INVEST), stratified by risk attributable to clinical severity of CAD (women with prior coronary events of myocardial infarction or revascularization considered high risk, all others at low risk) and by age group (50-64 or ≥65 years). The prognostic impact of achieving mean in-trial SBP <130 (referent group) was compared with 130-139 and ≥ 140 mmHg using Cox proportional hazards, adjusting for demographic and clinical characteristics.

Results: SBPs <130, 130-139, and ≥140 were achieved in 2960, 3024, and 3232 women, respectively. Among high-risk women aged ≥65 years, those achieving SBP 130-139 mmHg had lower mortality up to 16.7 years later than those with SBP <130 (hazard ratio [HR] 0.81, 95% CI 0.69-0.96). High-risk women aged 50-64 achieving SBP 130-139 had a similar mortality risk as those with SBP <130 (HR 1.21, 95% CI 0.87-1.68), while those achieving SBP ≥140 mmHg had a higher mortality risk than SBP < 130 (HR 1.92, 95% CI 1.37-2.68). A similar pattern was observed among low-risk women ≥65 and <65 years old.

Conclusion: Among women ≥65 years old with hypertension and prior coronary events, in-trial SBP between 130 and 139 mmHg was associated with lower mortality over the long term versus SBP <130 mmHg.
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http://dx.doi.org/10.1016/j.ijchy.2020.100052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009246PMC
December 2020

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.

Genet Med 2021 07 29;23(7):1185-1191. Epub 2021 Mar 29.

Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, MD, USA.

Purpose: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions.

Methods: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation.

Results: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression.

Conclusion: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.
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http://dx.doi.org/10.1038/s41436-021-01118-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263480PMC
July 2021

Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.

Eur Heart J 2021 05;42(18):1742-1756

Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, 1462 Clifton Road NE, Atlanta, GA 30322, USA.

Aims: Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.

Methods And Results: We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.

Conclusion: The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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http://dx.doi.org/10.1093/eurheartj/ehab107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244638PMC
May 2021

Rationale and design of the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial.

Am Heart J 2021 07 18;237:90-103. Epub 2021 Mar 18.

Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL.

Background: Approximately half of all women with anginal symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) referred for coronary angiography have elevated risk for major adverse cardiac events (MACE), poor quality of life and resource consumption. Yet, guidelines focus on symptom management while clinical practice typically advocates only reassurance. Pilot studies of INOCA subjects suggest benefit with intensive medical therapy (IMT) that includes high-intensity statins and angiotensin converting enzyme inhibitors (ACE-I) or receptor blockers (ARB) to provide the rationale for a randomized pragmatic trial to limit MACE.

Methods: The Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) of a pragmatic strategy of IMT vs usual care (UC) in 4,422 symptomatic women with INOCA (NCT03417388) in approximately 70 United States sites. The hypothesis is that IMT will reduce the primary outcome of first occurrence of MACE by 20% vs. UC at ∼2.5 year followup. Secondary outcomes include quality of life, time to return to "duty"/work, healthcare utilization, angina, cardiovascular death and individual primary outcome components over 3 years follow-up. The study utilizes web-based data capture, e-consents, single IRB and centralized pharmacy distribution of strategy medications directly to patients' homes to reduce site and patient burden. A biorepository will collect blood samples to assess potential mechanisms.

Conclusions: The results of this trial will provide important data necessary to inform guidelines regarding how best to manage this growing and challenging population of women with INOCA.
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http://dx.doi.org/10.1016/j.ahj.2021.03.011DOI Listing
July 2021

Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center.

Cardiooncology 2021 Mar 18;7(1):10. Epub 2021 Mar 18.

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, PO Box 100486, 1345 Center Drive, Gainesville, FL, 32610-0486, USA.

Background: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center.

Methods: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment.

Results: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006).

Conclusions: This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.
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http://dx.doi.org/10.1186/s40959-021-00097-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977591PMC
March 2021

Race-Specific Comparisons of Antihypertensive and Metabolic Effects of Hydrochlorothiazide and Chlorthalidone.

Am J Med 2021 07 9;134(7):918-925.e2. Epub 2021 Jan 9.

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida; Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, Florida. Electronic address:

Background: Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites vs blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients.

Methods: We compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks; 25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional 6 weeks) of PEAR-2 (n = 326) clinical trials, in 17-65-year-old mild-moderate uncomplicated hypertensive whites and blacks.

Results: Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval, 0.07-0.37; P = 3.4e).

Conclusion: Compared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting that the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks.
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http://dx.doi.org/10.1016/j.amjmed.2020.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243781PMC
July 2021

Implications of Polymorphisms in the BCKDK and GATA-4 Gene Regions on Stable Warfarin Dose in African Americans.

Clin Transl Sci 2021 03 16;14(2):492-496. Epub 2020 Dec 16.

Department of Pharmacotherapy & Translational Research, Center for Pharmacogenomics & Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

VKORC1 and CYP2C9 genotypes explain less variability in warfarin dose requirements in African Americans compared with Europeans. Variants in BCKDK and GATA-4 gene regions, purported to regulate VKORC1 and CYP2C9 expression, have been shown to play an important role in warfarin dose requirements in Europeans and Asians, respectively. We sought to determine whether rs56314408 near BCKDK or GATA-4 rs2645400 influence warfarin dose requirements in 200 African Americans. Unlike the strong linkage disequilibrium (LD) between rs56314408 and VKORC1 rs9923231 in Europeans, they were not in LD in African Americans. No associations were found on univariate analysis. On multivariable analysis, rs56314408 was associated (P = 0.027) with dose in a regression model excluding VKORC1 rs9923231, and GATA-4 rs2645400 was associated (P = 0.032) with dose in a model excluding CYP2C (CYP2C9*2, *3, *5, *6, *8, and *11, CYP2C rs12777823) variants. Neither variant contributed to dose in the model that included both VKORC1 rs9923231 and CYP2C variants. Our results do not support contributions of the studied variants to warfarin dose requirements in African Americans. However, they illustrate the value of studies in African descent populations, who have low LD in their genome, in teasing out genetic variation underlying drug response associations. They also emphasize the importance of confirming associations in persons of African ancestry.
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http://dx.doi.org/10.1111/cts.12939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993290PMC
March 2021

Optimizing Precision of Hypertension Care to Maximize Blood Pressure Control: A Pilot Study Utilizing a Smartphone App to Incorporate Plasma Renin Activity Testing.

Clin Transl Sci 2021 03 30;14(2):617-624. Epub 2020 Nov 30.

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

Only half of patients with hypertension (HTN) respond to any given antihypertensive medication. Heterogeneity in pathophysiologic pathways underlying HTN is a major contributor. Personalizing antihypertensive therapy could improve blood pressure (BP) reduction. The objective of this study was to assess the effect of pragmatic implementation of a personalized plasma renin activity (PRA)-based smartphone app on improving BP reduction. Patients with untreated or treated but uncontrolled HTN were recruited. BP and PRA were measured at baseline with final BP measured at 6 months. Patient's information was entered into the app and treatment recommendations were returned. Clinicians were at liberty to follow or disregard the app's recommendations. BP levels and percent BP control among patients whose clinicians did and did not follow the app's recommendations were compared using independent t-test and Fisher's exact test, respectively. Twenty-nine European American patients were included (38% women) with mean age of 52 ± 9 years and median PRA of 1.3 ng/mL/hr (interquartile range 0.5-3.1 ng/mL/hr). Participants whose clinicians followed the app's recommendations (n = 16, 55%) as compared with those whose clinicians did not (n = 13, 45%), had a greater reduction in 6-month systolic BP (-15 ± 21 vs. -3 ± 21 mm Hg; adjusted-P = 0.1) and diastolic BP (-8 ± 8 vs. -1 ± 8 mm Hg; adjusted-P = 0.04). BP control at 6 months tended to be greater among patients whose clinicians accepted the app's recommendations vs. those whose clinicians did not (63% vs. 23%, P = 0.06). This pilot study demonstrates that acceptance of the app's recommendations was associated with a greater BP reduction. Future studies to confirm these pilot findings are warranted.
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http://dx.doi.org/10.1111/cts.12922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993275PMC
March 2021

Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.

CPT Pharmacometrics Syst Pharmacol 2020 12 3;9(12):678-685. Epub 2020 Nov 3.

Department of Pharmacotherapy and Translation Research, Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2-2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25-1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25-1.5 vs. 2-2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (-10.8 ± 5.5) vs. 2-2.25 (-7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25-1.5 (-9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.
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http://dx.doi.org/10.1002/psp4.12563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762806PMC
December 2020

Attended vs unattended systolic blood pressure measurement: A randomized comparison in patients with cardiovascular disease.

J Clin Hypertens (Greenwich) 2020 11 20;22(11):1987-1992. Epub 2020 Sep 20.

Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, Gainesville, FL, USA.

Recent clinical guidelines recommend lower blood pressure (BP) goals for most patients, and recent trends have favored use of automated unattended BP measurements in the office setting to minimize observer error and white-coat effects. Patients attending a routinely scheduled CVD clinic visit were prospectively randomized to BP measured using an attended, followed by an unattended method, or vice versa, after a controlled rest period. All study BP measurements were obtained in triplicate using the automated Omron HEM-907XL BP monitor, and averaged. The outcome was difference in SBP. Routinely measured clinic BP from the same visit was extracted from the medical record, and compared with attended and unattended BP. A total of 102 patients were randomized, and mean age was 63 years, 52% female and 75% Caucasian. Attended and unattended SBP was 125.4 ± 20.4 and 122.6 ± 21.0 mm Hg, mean ± SD, respectively. Routine clinic SBP was 130.6 ± 23.6 mm Hg. Attended SBP was 2.7 mm Hg higher than the unattended measurement (95% CI 1.3-4.1; P = .0002). Routine clinic SBP was 5.2 mm Hg higher than attended SBP (95% CI 2.4-8.0; P = .0003) and 8.0 mm Hg higher than unattended SBP (95% CI 5.4-10.5; P < .0001). Attended measurement of BP is significantly higher than unattended measurement and the difference is physiologically meaningful, even in a CVD cohort with generally well-controlled hypertension. Furthermore, routine clinic SBP substantially overestimates both attended and unattended automated SBP, with important implications for treatment decisions like dose and/or drug escalation.
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http://dx.doi.org/10.1111/jch.14037DOI Listing
November 2020

Genotype-Guided Hydralazine Therapy.

Am J Nephrol 2020 14;51(10):764-776. Epub 2020 Sep 14.

Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA,

Background: Despite its approval in 1953, hydralazine hydrochloride continues to be used in the management of resistant hypertension, a condition frequently managed by nephrologists and other clinicians. Hydralazine hydrochloride undergoes metabolism by the N-acetyltransferase 2 (NAT2) enzyme. NAT2 is highly polymorphic as approximately 50% of the general population are slow acetylators. In this review, we first evaluate the link between NAT2 genotype and phenotype. We then assess the evidence available for genotype-guided therapy of hydralazine, specifically addressing associations of NAT2 acetylator status with hydralazine pharmacokinetics, antihypertensive efficacy, and toxicity.

Summary: There is a critical need to use hydralazine in some patients with resistant hypertension. Available evidence supports a significant link between genotype and NAT2 enzyme activity as 29 studies were identified with an overall concordance between genotype and phenotype of 92%. The literature also supports an association between acetylator status and hydralazine concentration, as fourteen of fifteen identified studies revealed significant relationships with a consistent direction of effect. Although fewer studies are available to directly link acetylator status with hydralazine antihypertensive efficacy, the evidence from this smaller set of studies is significant in 7 of 9 studies identified. Finally, 5 studies were identified which support the association of acetylator status with hydralazine-induced lupus. Clinicians should maintain vigilance when prescribing maximum doses of hydralazine. Key Messages: NAT2 slow acetylator status predicts increased hydralazine levels, which may lead to increased efficacy and adverse effects. Caution should be exercised in slow acetylators with total daily hydralazine doses of 200 mg or more. Fast acetylators are at risk for inefficacy at lower doses of hydralazine. With appropriate guidance on the usage of NAT2 genotype, clinicians can adopt a personalized approach to hydralazine dosing and prescription, enabling more efficient and safe treatment of resistant hypertension.
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http://dx.doi.org/10.1159/000510433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606720PMC
September 2021

Optimizing identification of resistant hypertension: Computable phenotype development and validation.

Pharmacoepidemiol Drug Saf 2020 11 26;29(11):1393-1401. Epub 2020 Aug 26.

Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA.

Purpose: Computable phenotypes are constructed to utilize data within the electronic health record (EHR) to identify patients with specific characteristics; a necessary step for researching a complex disease state. We developed computable phenotypes for resistant hypertension (RHTN) and stable controlled hypertension (HTN) based on the National Patient-Centered Clinical Research Network (PCORnet) common data model (CDM). The computable phenotypes were validated through manual chart review.

Methods: We adapted and refined existing computable phenotype algorithms for RHTN and stable controlled HTN to the PCORnet CDM in an adult HTN population from the OneFlorida Clinical Research Consortium (2015-2017). Two independent reviewers validated the computable phenotypes through manual chart review of 425 patient records. We assessed precision of our computable phenotypes through positive predictive value (PPV) and test validity through interrater reliability (IRR).

Results: Among the 156 730 HTN patients in our final dataset, the final computable phenotype algorithms identified 24 926 patients with RHTN and 19 100 with stable controlled HTN. The PPV for RHTN in patients randomly selected for validation of the final algorithm was 99.1% (n = 113, CI: 95.2%-99.9%). The PPV for stable controlled HTN in patients randomly selected for validation of the final algorithm was 96.5% (n = 113, CI: 91.2%-99.0%). IRR analysis revealed a raw percent agreement of 91% (152/167) with Cohen's kappa statistic = 0.87.

Conclusions: We constructed and validated a RHTN computable phenotype algorithm and a stable controlled HTN computable phenotype algorithm. Both algorithms are based on the PCORnet CDM, allowing for future application to epidemiological and drug utilization based research.
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http://dx.doi.org/10.1002/pds.5095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754782PMC
November 2020

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Circulation 2020 08 13;142(6):546-555. Epub 2020 Jul 13.

Department of Cardiology, Division Heart and Lungs (V.T., A.F.S., J.v.S., A.O.K., F.W.A.), UMC Utrecht, Utrecht University, the Netherlands.

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.

Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.

Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; =28%; -heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.

Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493828PMC
August 2020

How to Transition from Single-Gene Pharmacogenetic Testing to Preemptive Panel-Based Testing: A Tutorial.

Clin Pharmacol Ther 2020 09 6;108(3):557-565. Epub 2020 Jul 6.

Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA.

There have been significant advancements in precision medicine and approaches to medication selection based on pharmacogenetic results. With the availability of direct-to-consumer genetic testing and growing awareness of genetic interindividual variability, patient demand for more precise, individually tailored drug regimens is increasing. The University of Florida (UF) Health Precision Medicine Program (PMP) was established in 2011 to improve integration of genomic data into clinical practice. In the ensuing years, the UF Health PMP has successfully implemented several single-gene tests to optimize the precision of medication prescribing across a variety of clinical settings. Most recently, the UF Health PMP launched a custom-designed pharmacogenetic panel, including pharmacogenes relevant to supportive care medications commonly prescribed to patients undergoing chemotherapy treatment, referred to as "GatorPGx." This tutorial provides guidance and information to institutions on how to transition from the implementation of single-gene pharmacogenetic testing to a preemptive panel-based testing approach. Here, we demonstrate application of the preemptive panel in the setting of an adult solid tumor oncology clinic. Importantly, the information included herein can be applied to other clinical practice settings.
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http://dx.doi.org/10.1002/cpt.1912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704727PMC
September 2020

Sorting nexin 1 loss results in increased oxidative stress and hypertension.

FASEB J 2020 06 15;34(6):7941-7957. Epub 2020 Apr 15.

Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Acute renal depletion of sorting nexin 1 (SNX1) in mice results in blunted natriuretic response and hypertension due to impaired dopamine D receptor (D R) activity. We elucidated the molecular mechanisms for these phenotypes in Snx1 mice. These mice had increased renal expressions of angiotensin II type 1 receptor (AT R), NADPH oxidase (NOX) subunits, D R, and NaCl cotransporter. Basal reactive oxygen species (ROS), NOX activity, and blood pressure (BP) were also higher in Snx1 mice, which were normalized by apocynin, a drug that prevents NOX assembly. Renal proximal tubule (RPT) cells from hypertensive (HT) Euro-American males had deficient SNX1 activity, impaired D R endocytosis, and increased ROS compared with cells from normotensive (NT) Euro-American males. siRNA-mediated depletion of SNX1 in RPT cells from NT subjects led to a blunting of D R agonist-induced increase in cAMP production and decrease in Na transport, effects that were normalized by over-expression of SNX1. Among HT African-Americans, three of the 12 single nucleotide polymorphisms interrogated for the SNX1 gene were associated with a decrease in systolic BP in response to hydrochlorothiazide (HCTZ). The results illustrate a new paradigm for the development of hypertension and imply that the trafficking protein SNX1 may be a crucial determinant for hypertension and response to antihypertensive therapy.
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http://dx.doi.org/10.1096/fj.201902448RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643053PMC
June 2020

New Drugs Approved in 2019.

Am J Med 2020 06 5;133(6):675-678. Epub 2020 Mar 5.

Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Fla. Electronic address:

In 2019, the US Food and Drug Administration (FDA) approved 48 novel drugs. Thirty of the 48 (62.5%) novel drug approvals were reviewed and approved through an expedited review pathway while 20 of the 48 (41.7%) were approved for treatment of a rare disease. This review includes a summary of the novel drugs approved by the FDA in 2019.
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http://dx.doi.org/10.1016/j.amjmed.2020.01.030DOI Listing
June 2020

The PCORnet Blood Pressure Control Laboratory: A Platform for Surveillance and Efficient Trials.

Circ Cardiovasc Qual Outcomes 2020 03 6;13(3):e006115. Epub 2020 Mar 6.

Department of Pharmacotherapy and Translational Research, University of Florida, College of Pharmacy, Gainesville, FL (R.M.C.D.).

Background: Uncontrolled blood pressure (BP) is a leading preventable cause of death that remains common in the US population despite the availability of effective medications. New technology and program innovation has high potential to improve BP but may be expensive and burdensome for patients, clinicians, health systems, and payers and may not produce desired results or reduce existing disparities in BP control.

Methods And Results: The PCORnet Blood Pressure Control Laboratory is a platform designed to enable national surveillance and facilitate quality improvement and comparative effectiveness research. The platform uses PCORnet, the National Patient-Centered Clinical Research Network, for engagement of health systems and collection of electronic health record data, and the Eureka Research Platform for eConsent and collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. Three demonstration projects are underway: BP track will conduct national surveillance of BP control and related clinical processes by measuring theory-derived pragmatic BP control metrics using electronic health record data, with a focus on tracking disparities over time; BP MAP will conduct a cluster-randomized trial comparing effectiveness of 2 versions of a BP control quality improvement program; BP Home will conduct an individual patient-level randomized trial comparing effectiveness of smartphone-linked versus standard home BP monitoring. Thus far, BP Track has collected electronic health record data from over 826 000 eligible patients with hypertension who completed ≈3.1 million ambulatory visits. Preliminary results demonstrate substantial room for improvement in BP control (<140/90 mm Hg), which was 58% overall, and in the clinical processes relevant for BP control. For example, only 12% of patients with hypertension with a high BP measurement during an ambulatory visit received an order for a new antihypertensive medication.

Conclusions: The PCORnet Blood Pressure Control Laboratory is designed to be a reusable platform for efficient surveillance and comparative effectiveness research; results from demonstration projects are forthcoming.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006115DOI Listing
March 2020

Optimizing Antihypertensive Medication Classification in Electronic Health Record-Based Data: Classification System Development and Methodological Comparison.

JMIR Med Inform 2020 Feb 27;8(2):e14777. Epub 2020 Feb 27.

Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, United States.

Background: Computable phenotypes have the ability to utilize data within the electronic health record (EHR) to identify patients with certain characteristics. Many computable phenotypes rely on multiple types of data within the EHR including prescription drug information. Hypertension (HTN)-related computable phenotypes are particularly dependent on the correct classification of antihypertensive prescription drug information, as well as corresponding diagnoses and blood pressure information.

Objective: This study aimed to create an antihypertensive drug classification system to be utilized with EHR-based data as part of HTN-related computable phenotypes.

Methods: We compared 4 different antihypertensive drug classification systems based off of 4 different methodologies and terminologies, including 3 RxNorm Concept Unique Identifier (RxCUI)-based classifications and 1 medication name-based classification. The RxCUI-based classifications utilized data from (1) the Drug Ontology, (2) the new Medication Reference Terminology, and (3) the Anatomical Therapeutic Chemical Classification System and DrugBank, whereas the medication name-based classification relied on antihypertensive drug names. Each classification system was applied to EHR-based prescription drug data from hypertensive patients in the OneFlorida Data Trust.

Results: There were 13,627 unique RxCUIs and 8025 unique medication names from the 13,879,046 prescriptions. We observed a broad overlap between the 4 methods, with 84.1% (691/822) to 95.3% (695/729) of terms overlapping pairwise between the different classification methods. Key differences arose from drug products with multiple dosage forms, drug products with an indication of benign prostatic hyperplasia, drug products that contain more than 1 ingredient (combination products), and terms within the classification systems corresponding to retired or obsolete RxCUIs.

Conclusions: In total, 2 antihypertensive drug classifications were constructed, one based on RxCUIs and one based on medication name, that can be used in future computable phenotypes that require antihypertensive drug classifications.
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http://dx.doi.org/10.2196/14777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068459PMC
February 2020

Thiazide Exposure and Cardiovascular Risk in Type 2 Diabetes Mellitus: A Point of Clarification.

Hypertension 2020 03 3;75(3):e2-e5. Epub 2020 Feb 3.

From the Department of Pharmacotherapy and Translational Research (S.M.S., R.M.C.-D.), University of Florida, Gainesville.

A recently published analysis in suggests that thiazide use, versus nonuse, is associated with excess risk of adverse cardiovascular outcomes in patients with diabetes mellitus enrolled in the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes). Here, we replicate these findings using the same publicly available datasets and following their reported methods. We further show that possible misclassification of thiazide exposure exists in the original analysis. We perform alternative analyses that correct for this misclassification to highlight the impact that misclassification can have on observed associations between an exposure (eg, thiazides) and outcomes (eg, stroke and major adverse cardiovascular events).
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035168PMC
March 2020

Redefining Resistant Hypertension: A Comparison of Cardiovascular Risk Associated With the 2018 Versus 2008 American Heart Association Definitions for Resistant Hypertension.

Circ Cardiovasc Qual Outcomes 2020 02 3;13(2):e005979. Epub 2020 Feb 3.

Department of Pharmacotherapy & Translational Research (S.M.S., R.M.C.-D.), College of Medicine, University of Florida, Gainesville.

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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.005979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006690PMC
February 2020

Response to: Heterogeneous Treatment Response by Race Cannot Be Claimed in the Absence of Evidence.

Am J Hypertens 2020 02;33(2):e2

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida.

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http://dx.doi.org/10.1093/ajh/hpz168DOI Listing
February 2020

Combination Antihypertensive Therapy Prescribing and Blood Pressure Control in a Real-World Setting.

Am J Hypertens 2020 04;33(4):316-324

Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA.

Background: Specific combinations of two drug classes are recommended in a variety of clinical situations in the management of hypertension. These preferred combinations are based on complimentary blood pressure (BP) lowering mechanisms or benefit for a concomitant disease.

Methods: Using electronic health records (EHRs) data from 27,579 ambulatory hypertensive patients, we investigated antihypertensive therapy prescribing patterns and associations of preferred two drug classes with BP control.

Results: Overall, BP control, defined as BP <140/90 mm Hg, was 65% among treated patients. Preferred dual antihypertensive therapy was prescribed in 55% of patients with uncomplicated hypertension, 49% of patients with diabetes, and 47% of patients with a history of myocardial infarction (MI); these prescribing frequencies of preferred combinations were not explained by worse BP control on those combinations. In fact, we found suggestive evidence of association between prescribing of preferred two drug classes and improved BP control among post-MI (OR: 1.21, 95% CI: 0.99-1.48, P = 0.061) and uncomplicated hypertensive (OR: 1.11, 95% CI: 0.98-1.26, P = 0.089) patients.

Conclusions: Prescribing of guideline-recommended antihypertensive drug classes for concomitant diseases is suboptimal and prescribing of preferred/optimized drug class combinations was moderate. We did not find a clear association between the use of optimized drug class combinations and greater BP control. Overall, using EHR data, we identified potential opportunities for re-examining prescribing practices with implications for clinical decision support and healthcare improvement at the community and health system-wide levels.
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http://dx.doi.org/10.1093/ajh/hpz196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109351PMC
April 2020
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