Steven M Smith

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

Importance Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) offer effective migraine-specific preventive treatment. However, concerns exist about their potential cardiovascular risks due to CGRP blockade. Objective To compare the incidence of cardiovascular disease (CVD) between Medicar...

Aim To comprehensively evaluate the benefits and risks of glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium‐glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to...

Background: Two classes of newer glucose-lowering drugs (GLDs), sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, improve cardiovascular and renal outcomes among patients with type 2 diabetes (T2D). However, racial and ethnic minority groups carry higher cardiovascular risks but have lower access to newer GLD...

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β‐blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vaso...

Background Sacubitril/valsartan, an angiotensin receptor/neprilysin inhibitor (ARNi), improves heart failure (HF) outcomes, yet real-world adherence patterns are not well understood. Objectives The purpose of this study was to analyze longitudinal patterns of adherence to ARNis in patients with HF and to identify factors associated with adherence...

The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tra...

Both short‐acting (epoetin alfa or beta) and long‐acting (darbepoetin alfa or PEG‐epoetin) erythropoiesis‐stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all‐cause mortality associated with receipt of sh...

Background: The COVID-19 pandemic resulted in reduced in-person clinic visits and declines in blood pressure (BP) control among patients with hypertension. The purpose of this study was to report on pre- to post-pandemic trends in BP control and related BP metrics through 2022. Methods: We utilized data from 17 US health systems with electronic hea...

Purpose Sacubitril/valsartan (SAC/VAL) or angiotensin receptor blockers (ARBs) are recommended therapy for heart failure with preserved ejection fraction (HFpEF), but little is known about their real-world comparative effectiveness among patients with HFpEF. The objective of this study was to determine the comparative effectiveness of SAC/VAL vs AR...

Background Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation...

Background Despite their frequent concurrent use, little is known about the concomitant use of calcium channel blockers (CCBs) and selective serotonin reuptake inhibitors (SSRIs) on fracture risk. We compared risk of fractures in patients concomitantly treated with CCBs and SSRIs versus CCB-only users. We compared risk of fractures among concomitan...

Minocycline, an anti-inflammatory antibiotic drug, rebalances impaired gut microbiota, attenuates neuroinflammation and lowers high blood pressure in animal models of hypertension and in hypertensive patients. Our objective in this study was to investigate if antihypertensive effects of minocycline involve the expression of gut epithelial genes rel...

Introduction Clinicians may prescribe new medications (marker drug) to treat statin‐related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence o...

Introduction: Routine follow-up (f/u) leads to better BP control and CV outcomes in individuals with hypertension (HTN). Guidelines suggest newly treated patients f/u within 1-2 months after initiating treatment. Few real-world studies have assessed the timing of actual f/u care and concordance with guidelines. Methods: We performed a cohort study...

Background: Initial antiHTN regimen intensity varies across patients, presumably due to factors like age, comorbidities, or baseline BP. However, the extent to which initial regimen intensity is influenced by patient factors, versus provider characteristics or preferences, and health system contexts, is unknown. Methods: We conducted a cross-sectio...

Introduction: Hypertension (HTN) is a complex condition with significant heterogeneity in presentation and treatment response. Identifying distinct subphenotypes of HTN may improve our understanding of its underlying mechanisms and guide more precise treatment or public health initiatives. Methods: Using EHR data from the OneFlorida+ research conso...

Introduction: ACEIs are the most commonly prescribed antiHTN drugs, but side effects may prompt additional therapy resulting in a prescribing cascade. We aimed to identify potential ACEI-induced prescribing cascades using high throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) national samples of Medica...

Introduction: ARBs are considered first-line antiHTN therapy, but side effects may prompt additional therapy resulting in prescribing cascades. We sought to screen for potential ARB-induced prescribing cascades during real-world use via high-throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) samples of...

Introduction: Thiazide diuretics are effective but can cause adverse effects that prompt the use of additional therapy, i.e., a prescribing cascade. We aimed to identify potential thiazide-induced prescribing cascades using high throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) samples of Medicare fee-...

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 wi...

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...