Steven M Smith

University of Florida | UF · Department of Pharmacotherapy and Translational Research

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended by the American Heart Association for management of heart failure with preserved ejection fraction (HFpEF), but little is known about their in-class comparative effectiveness in real-world settings. Objectives: To assess the comparative effectiveness of SGLT2i for pre...

While opioid prescribing has significantly decreased from a peak in 2012, less is known about the national utilization of non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP) in the context of the opioid crisis. The objective of this study is to characterize the prescribing trends of NSAIDs and APAP...

Objective: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. Patients and methods: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of t...

Purpose: Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin-related prescribing cascades has been performed to our knowledge. Methods: We utilized sequence symmetry analysis to iteratively screen p...

Introduction: Early treatment for hypertension (HTN) portends better outcomes. However, few real-world studies have assessed initial antiHTN regimens and how they differ by baseline blood pressure (BP). We sought to compare initial treatment patterns, stratified by BP, between Medicaid and Medicare recipients. Methods: We performed a cross-sectiona...

Study objective Half of patients with heart failure have preserved ejection fraction (HFpEF). Over the years, guidelines have recommended or advised against various therapies for HFpEF management. However, there is limited evidence on the trends in utilization of the various medications. The aim of this study was to examine the trends in the use of...

Background Knowledge of real‐world antihypertensive use is limited to prevalent hypertension, limiting our understanding of how treatment evolves and its contribution to persistently poor blood pressure control. We sought to characterize antihypertensive initiation among new users. Methods and Results Using Medicaid and Medicare data from the OneF...

Background: The use of a new medication (e.g., potassium supplementation) for managing a drug-induced adverse event (e.g., loop diuretic-induced hypokalemia) constitutes a prescribing cascade. However, loop diuretics are often stopped while potassium may be unnecessarily continued (i.e., relic). We aimed to quantify the occurrence of relics using...

Background Sepsis and septic shock are associated with significant morbidity and mortality. Rapid initiation of appropriate antibiotic therapy is essential, as inadequate therapy early during septic shock has been shown to increase the risk of mortality. However, despite the importance of appropriate antibiotic initiation, in clinical practice, con...

Patients with higher genetic West African ancestry (GWAA) have hypertension (HTN) that is more difficult to treat and have higher rates of cardiovascular diseases (CVD) and differential responses to antihypertensive drugs than those with lower GWAA. The mechanisms underlying these disparities are poorly understood. Using data from 84 ancestry-infor...

Background: Limited evidence exists regarding long-term effectiveness and safety of aldosterone antagonists (AAs) versus beta blockers (BBs) as fourth-line antihypertensive agents in patients with resistant hypertension (RH). We evaluated the comparative effectiveness and safety of aldosterone AA versus BB. Methods: We conducted a real-world ret...

Objectives: The 2016 U.S. presidential election was a major source of stress among many adults. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Little is known regarding the association of macro-level sociopolitical events with BP changes at the population-level. This study sought to characterize population-level...

Understanding differences in risk factors can assist in identifying means to reduce racial/ethnic disparities in type 2 diabetes (T2D) prevalence. Different types of blood pressure (BP) lowering drugs are associated with different levels of T2D risk. This study examined the utilization of BP-lowering drugs among US adults aged 18 and over without d...

Background and objectives: In 2011, the Centers for Medicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing. Design, setting, participants, & measurements...

The risk of obstructive sleep apnea (OSA) in patients with resistant hypertension (RH) has not been well-quantified. We sought to evaluate the risk of OSA in patients with RH compared to those with treated but non-resistant hypertension (non-RH) using a time-dependent-exposure analysis. We conducted a retrospective cohort study of patients with tre...

Study objective: To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression. Design: Retrospective cohort st...

BACKGROUND Whether the cardiorenal benefits of sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are comparable between White and Asian populations remains unclear. PURPOSE To compare the cardiorenal benefits of SGLT2 inhibitors and GLP-1RAs between White and Asian populations and to compare...

SARS-CoV-2 accesses host cells via angiotensin-converting enzyme-2, which is also affected by commonly used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), raising concerns that ACEI or ARB exposure may portend differential COVID-19 outcomes. In parallel cohort studies of outpatient and inpatient COVID-19-...

Introduction: Blood pressure (BP) varies seasonally, typically manifesting as increased BP during the winter and reduced BP during the summer, that may contribute to difficulty in maintaining BP control among individuals with hypertension. We investigated seasonal differences in population-level BP control among U.S. adults with hypertension and wh...

Background: Drug-related adverse events associated with antihypertensive therapy may result in subsequent prescribing of other potentially harmful medications, known as prescribing cascades. The aim of this study was to assess the magnitude and characteristics of a beta-blocker - edema - loop diuretic prescribing cascade. Methods: A prescription...

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 Respons...

Introduction Antihypertensive medication nonadherence is a prevalent issue but is very difficult to accurately assess. To clarify this problem among hypertensive patients attending a cardiovascular disease outpatient clinic, we utilized high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) to assess antihypertensive medication a...

Study objective: To assess the effectiveness of sacubitril/valsartan versus angiotensin receptor antagonist therapy for prevention of heart failure (HF)-related hospitalization and all-cause hospitalization in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF). Design: Retrospective cohort study. Data source:...

Introduction: Politics are a major source of stress and anxiety among U.S. adults, and the 2016 U.S. general election may have led to increased psychosocial stress among different racial/ethnic populations. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Yet, little is known regarding whether this response differs...

Introduction: A fixed-dose combination of amlodipine and celecoxib, branded in the USA as Consensi®, was recently granted a US Food and Drug Administration (FDA)-approved indication for treatment of comorbid hypertension and osteoarthritis. Areas covered: A PubMed and Medline search was conducted for clinical trials published through December 2020...

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 patien...

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...

Only half of hypertensive patients respond to any given antihypertensive. Heterogeneity in pathophysiologic pathways underlying hypertension (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 personali...

Introduction The Women's Ischemia Syndrome Evaluation (WISE) studies observed that majority of women undergoing coronary angiography for symptoms/signs of ischemia have no obstructive coronary artery disease (INOCA) but have an increased risk of major adverse cardiac events (MACE) exceeding 2.5% yearly by 5 years. Identifying modifiable and non-mod...

Background: Nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased risk of adverse cardiovascular events prompting labeling revisions cautioning their use among patients with cardiovascular disease (CVD). However, little is known regarding long-term trends in real-world prescribing of NSAIDs within the CVD population. We...

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 at...

Background: Clinical guidelines increasingly recommended ambulatory blood pressure monitoring (ABPM) for hypertension diagnosis and management. Yet, ABPM is used infrequently in the United States, possibly because of low insurance coverage and high patient costs. We sought to analyze out-of-pocket payments (OPPs) for ABPM among privately insured p...

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-ca...

Purpose There is limited evidence to support the use of direct-acting oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and active cancer. This study aimed to assess the effectiveness of DOACs versus warfarin for the prevention of recurrent VTE and major bleeding events in patients with VTE and active cancer. Methods We ide...

Background Metabolic syndrome (MetS) is a risk factor for the development of cardiovascular disease and type 2 diabetes. Although the development of MetS is attributed to known lifestyle factors, perceived discrimination may also contribute to MetS development and severity. Purpose We examined the associations of perceived discrimination with MetS...

Background Ambulatory blood pressure monitoring (ABPM) has been increasingly recommended for diagnosis confirmation and monitoring in patients with new-onset hypertension and apparent treatment-resistant hypertension (aTRH). We assessed insurance claims submitted for ABPM among a nationally representative sample of commercially insured U.S. patient...

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and inflammation, but their ubiquitous use has led to concerns over increased risk of adverse cardiovascular (CV) events, particularly in patients with established CV disease (CVD). In 2005, the FDA revised labels for all NSAIDs to include a boxed wa...

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...

A recently published analysis in Hypertension 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 a...

Purpose Compared with conventional therapy (enoxaparin followed by warfarin), the direct-acting oral anticoagulant apixaban is thought to offer similar protection against recurrent venous thromboembolism (VTE) with lower bleeding risk. However, evidence regarding the heterogeneity of treatment effect from real-world data is lacking. The study descr...

We conducted a cross‐sectional analysis using a database from commercial health plans in the United States to describe trends in the use of antidiabetic medications among patients with type‐2 diabetes and heart failure (HF) from 2006 through 2017. We used loop diuretic dose as a surrogate for HF severity (mild‐HF 0‐40 mg/day, moderate‐severe HF >40...

Ambulatory blood pressure monitoring (ABPM) is increasingly recommended for confirming hypertension diagnosis and ongoing hypertension monitoring. However, reimbursement in the United States is variable and low compared with other advanced health care systems. We examined the reimbursement of ABPM and factors associated with successful reimbursemen...

See Article Martınez-Mardones et al.

Background Hypertension (HTN) and coronary artery disease (CAD) are a prevalent combination in women, however limited data are available to guide blood pressure (BP) management. We hypothesize older women with HTN and CAD may not derive the same prognostic benefit from systolic BP (SBP) lowering <130 mmHg. Purpose To investigate the long-term mort...

Background: Antihypertensive medication nonadherence is believed to be a prevalent issue but is very difficult to accurately assess. As a result, using a variety methods, nonadherence rates ranging from 3-86% have been suggested. To clarify this problem among hypertensive patients attending a CVD outpatient clinic, we utilized high-performance liqu...

Objectives: Out-of-office BP measurement, including ambulatory and home BP monitoring (ABPM, HBPM, respectively) are considered the gold standard for hypertension and treatment-resistant hypertension (TRH) confirmation, but their real-world use is not well-studied. We examined recent trends in submitted claims for ABPM and HBPM among commercially-i...

Introduction: Nearly one half of the subjects in SPRINT had their blood pressure (BP) measured absent an observer (unattended), whereas most prior trials have used attended measurement. This has created controversy in interpreting the relationship between achieved systolic BP (SBP) and outcomes in SPRINT. Accordingly, we prospectively examined the...

Background: About half of patients with hypertension (HTN) respond to any given antihypertensive drug. Discordance in pathophysiologic pathways underlying HTN and anti-HTN mechanism of action are major contributors. Personalizing anti-HTN therapy could optimize blood pressure (BP) control. The objective of OPTI-BP was to assess the pragmatic implem...

Background: Hypertension is a major modifiable risk factor for coronary artery disease (CAD), the main cause of death in women. While association between the two is frequent, limited data exist regarding the feasibility of blood pressure (BP) management and outcomes in women across the spectrum of CAD. Accordingly, we analyzed patient characteristi...

BACKGROUND Computable phenotypes have the ability to utilize data within the electronic health record (EHR) in order to identify patients with certain characteristics. Many computable phenotypes rely on multiple types of data within the EHR including prescription drug information, which is the case for resistant hypertension (RHTN). RHTN is a pheno...

Recent guidelines call for more intensive blood pressure (BP)‐lowering and a less‐stringent treatment‐resistant hypertension (TRH) definition, both of which may increase the occurrence of this high‐risk phenotype. We performed a post hoc analysis of 11 784 SPRINT and ACCORD‐BP participants without baseline TRH, who were randomized to an intensive (...

Background Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may protect against aging-related decline. This study directly compared ACEis and ARBs on associations with risk of mobility disability in older adults when combined with a physical activity intervention. Methods This was a secondary analysis of the...

Objective: To review the pharmacology, efficacy, and safety of the calcitonin gene-related peptide (CGRP) inhibitor erenumab for migraine preventive therapy. Data sources: A MEDLINE/PubMed search (January 2000 to January 2019) was conducted using the keywords erenumab-aooe, erenumab, migraine, migraine prophylaxis, migraine prevention, and chron...

A recent observational study published in Pharmacotherapy suggests that treatment with an angiotensin receptor blocker (ARB), compared to an angiotensin‐converting enzyme (ACE) inhibitor, each combined with statin therapy, substantially reduces cardiovascular events and mortality in patients with newly‐diagnosed coronary heart disease. This Alterna...

Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. T...

The U.S. Food and Drug Administration recently granted an approved indication for the first fixed-dose combination antihypertensive (amlodipine) and non-steroidal anti-inflammatory drug (celecoxib) for treatment of comorbid hypertension and osteoarthritis. This review summarizes available data on this combination product, to be marketed as Consensi...

Background: Prior studies suggest benefits of blood pressure-lowering on cardiovascular risk may be attenuated in resistant hypertension compared to the general hypertensive population, but prospective data are lacking. Methods: We assessed intensive (<120 mmHg) versus standard (<140 mmHg) systolic blood pressure targets on adverse outcome risk...

Background: Withdrawing medications that interfere with blood pressure (BP) is recommended in patients with uncontrolled BP, yet real-world use of such agents is not well characterized among hypertensive individuals. We aimed to evaluate the use of BP-interfering prescription medications among U.S. patients with hypertension. Methods: This retro...

Aims: To determine the association between cardiovascular diseases (CVD) and SGLT2 inhibitors compared to sulfonylureas and dipeptidyl peptidase-4 (DPP4) inhibitors and to examine within-class effects of SGLT2 inhibitors. Methods: A retrospective cohort analysis was conducted using Truven Health MarketScan. New users of SGLT2 inhibitors, sulfony...

Background Incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon like peptide-1 (GLP-1) receptor agonists are novel medications for type 2 diabetes management. Several studies have found cardioprotective effects of incretin-based therapies; however, it remains unclear whether there is any difference in heart fail...

Background: In patients with stable international normalized ratios, 12-week extended-interval warfarin monitoring can be considered; however, predictors of success with this strategy are unknown. The previously validated SAMe-TT2R2 score (considering sex, age, medical history, treatment, tobacco, and race) predicts anticoagulation control during...

Introduction: Hypertension is highly prevalent in Florida, but surveillance through the Behavioral Risk Factor Surveillance System (BRFSS) is limited to self-reported hypertension and does not capture data on undiagnosed hypertension or measure blood pressure. We aimed to characterize the hypertensive population in the OneFlorida Clinical Research...

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of acute medically ill patients with venous thromboembolism (VTE) risk factors. Data sources: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted using the following keywords...

Objectives: A goal SBP 120 mmHg or less reduced mortality in high-risk Systolic Blood Pressure Intervention Trial patients; however, mortality implications of concomitant DBP lowering in coronary artery disease (CAD) are uncertain. We examined the relationship between DBP lowering and all-cause mortality with lower achieved SBPs in a large cohort....

Background: National Health and Nutrition Examination Survey (NHANES) data indicate only 50% with hypertension (HTN) have controlled blood pressure (BP) yet limited data are available regarding patient’s knowledge of and satisfaction with their BP control. Methods: We utilized MyHealthStory, an online health information exchange portal to identify...

Purpose of review: Emerging evidence suggests that multiple mechanisms may be responsible for the development of treatment-resistant hypertension (TRH). This review aims to summarize recent data on potential mechanisms of resistance and discuss current pharmacotherapeutic options available in the management of TRH. Recent findings: Excess sodium...

This retrospective cohort study compared administration of lisinopril twice daily and once daily for hypertension. Data were collected from an ambulatory electronic health record between 2011 and 2014. Patients previously receiving lisinopril 20 mg were placed into the once-daily cohort if changed to 40 mg once daily or into the twice-daily cohort...