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Publications (435)
Aims
In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF...
Background
The TRANSFORM-HF trial found no significant difference in all-cause mortality and all-cause hospitalization following hospitalization for heart failure (HF) with a diuretic strategy of torsemide versus furosemide. However, the impact of diuretic dosing on the trial results and whether the relationship between dosing and outcomes differs...
Aims
The VICTORIA trial demonstrated a significant reduction in the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death with vericiguat relative to placebo in high‐risk HF. This study aimed to contextualize treatment effects of vericiguat in populations with varying risk profiles simulated from the PARADIGM‐HF an...
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were desig...
Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic...
Aims
The TRANSFORM‐HF trial found no difference in clinical outcomes between torsemide versus furosemide after hospitalization for heart failure. This analysis aimed to assess the impact of diuretic dosing on the primary and secondary clinical outcomes.
Methods and results
This post‐hoc analysis of TRANSFORM‐HF categorized patients into three grou...
Aims:
Benefits of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved and mildly reduced ejection fraction (HFpEF/HFmrEF) have not been established. Conventional randomized controlled trials are complex and expensive. The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ej...
Importance
In 2013, the Trial to Assess Chelation Therapy (TACT) reported that edetate disodium (EDTA)–based chelation significantly reduced cardiovascular disease (CVD) events by 18% in 1708 patients with a prior myocardial infarction (MI).
Objective
To replicate the finding of TACT in individuals with diabetes and previous MI.
Design, Setting,...
Aim
The TRANSFORM‐HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non‐adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on‐treatment analysis...
Background
Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed.
Methods
We conducted a study to compare the current Steroids...
Aim
Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all‐cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half‐life, but direct supportive evi...
BACKGROUND
The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies di...
Rationale:
Oral microbiota associate with diseases of the mouth and serve as a source of lung microbiota. However, the role of oral microbiota in lung disease is unknown.
Objectives:
To determine associations between oral microbiota and disease severity and death in idiopathic pulmonary fibrosis.
Methods:
We analyzed 16S rRNA gene and shotgun...
Introduction. Post-acute sequelae of SARS-CoV2 infection, or PASC, is defined as the presence of persistent symptoms for at least two months after an acute infection with COVID-19. A potential pathophysiologic mechanism for PASC is microvascular thrombosis. Using EQ-5D-5L index scores, we previously reported that extended thromboprophylaxis for 30...
Aims
The relationship between accelerometry data and changes in Kansas City Cardiomyopathy Questionnaire‐Physical Limitation Score (KCCQ‐PLS) or 6 min walk test (6MWT) is not well understood.
Methods and results
VITALITY‐HFpEF accelerometry substudy ( n = 69) data were assessed at baseline and 24 weeks. Ordinal logistic regression models were used...
Importance
Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF).
Objectives
To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF.
Design, Setting, and Part...
Introduction: TRANSFORM-HF trial showed no significant difference in mortality or hospitalization outcomes in patients randomized to torsemide (T) versus furosemide (F) following a heart failure (HF) hospitalization (HFH). However, outcomes and responses to some therapies differ across ejection fraction (EF) subgroups.
Methods: We compared baseline...
Introduction: In the TRANSFORM HF trial, among patients discharged after hospitalization for heart failure (HF), torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months.
Hypothesis: Differences in clinical profiles, outcomes, and treatment effects may exist between de-novo and worsening ch...
Introduction: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization.
Hypothesis: Clinicians may favor torsemide in the setting of renal dysfunction due to better oral bioavailability and longer half-life. However, the impact of...
Background:
The VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) demonstrated that, in patients with high-risk heart failure, vericiguat reduced the primary composite outcome of cardiovascular death or heart failure hospitalization relative to placebo. The hazard ratio for all-cause mortality w...
Importance:
Guidelines recommend deferral of testing for symptomatic people with suspected coronary artery disease (CAD) and low pretest probability. To our knowledge, no randomized trial has prospectively evaluated such a strategy.
Objective:
To assess process of care and health outcomes in people identified as minimal risk for CAD when testing...
Importance:
Trials showing equivalent or better outcomes with initial evaluation using coronary computed tomography angiography (cCTA) compared with stress testing in patients with stable chest pain have informed guidelines but raise questions about overtesting and excess catheterization.
Objective:
To test a modified initial cCTA strategy desig...
Importance:
Immune dysregulation contributes to poorer outcomes in COVID-19.
Objective:
To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.
Design, setting, and participants:
Randomized, double-masked, placebo-controlled clinical trial using a master protocol to inv...
Background:
We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failur...
Objective
We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs).
Data sources
PubMed and EMBASE databases were searched to identify randomised trials studying HCQ.
Study selection
Ten RCTs were identified (n...
Background:
Heart failure hospitalization (HFH) is a major source or morbidity, consumes significant economic resources, and is a key endpoint in HF clinical trials. While HFH events vary in severity and implications, they are typically considered equivalent when analyzing clinical trial outcomes.
Objectives:
We aimed to evaluate the frequency a...
Background: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As pre-specified secondary endpoints, the TRANSFORM-HF trial compared the effect of torsemide versus furosemide on patient-reported outcomes...
Background:
Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.
Objective:
To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitaliza...
Background:
The association between frailty and health status in patients with heart failure with preserved ejection fraction (HFpEF) is not well known.
Objectives:
The authors examined the association between: 1) patient-reported frailty, measured by the Fried frailty phenotype, Kansas City Cardiomyopathy Questionnaire physical limitation score...
Background
Women with atrial fibrillation (AF) demonstrate more AF‐related symptoms and worse quality of life (QOL). Whether increased use of ablation in women reduces sex‐related QOL differences is unknown. Sex‐related outcomes for ablation versus drug therapy was a prespecified analysis in the CABANA (Catheter Ablation Versus Antiarrhythmic Drug...
Objective:
To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW).
Methods:
IN A 1: :1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCW at risk for COVID-19 infection were enrolled between April and No...
Importance:
Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide.
Objective:
To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure.
Design, setting, and participants:
TRANS...
In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it...
Background
Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if the TNF-alpha inhibitor, infliximab (IFX), provides additional benefit over standard of care.
Methods
We conducted a double-blin...
Background
Severe COVID-19 infection is characterized by a dysregulated hyperinflammatory state that contributes to morbidity and mortality. Immunomodulatory therapy has been shown to improve outcomes. We investigated if abatacept, CTLA-4-Ig, a selective costimulation modulator, provides additional benefit when added to standard of care.
Methods
W...
Background: In the VICTORIA trial in patients with heart failure with reduced ejection fraction, vericiguat (V) versus placebo (P) reduced the primary composite outcome (heart failure hospitalization [HFH] or cardiovascular death [CVD]) from 38.5 to 35.5% (1869 events: V=897, P=972) ( Fig A ). In this prespecified analysis, we assessed vericiguat’s...
Patients with heart failure with reduced ejection fraction (HFrEF) have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Sodium guanylate cyclase (sGC) stimulators have the potential to lower this risk by modifying the nitric oxide-sGC-cyclic guanosine mono...
Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.
Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abat...
Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care.
Methods: We conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants h...
Background
The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) trial, which evaluated sacubitril/valsartan in patients with advanced heart failure (HF) with reduced ejection fraction and recent New York Heart Association functional class IV symptomatology, did not require tolerance to a renin angiotensin system antagonist before initiating sac...
Background:
In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atria...
Background:
Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design.
Methods:
TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly i...
Introduction
A small subset of patients with heart failure with reduced ejection fraction (HFrEF) will have favorable reverse remodeling and improved left ventricular (LV) function. Patients with improved HFrEF have markedly better outcomes than other HFrEF patients, but the mechanisms that mediate reverse remodeling are poorly understood. Loss of...
Background:
Clinically important thresholds in patient-reported outcomes measures like the Kansas City Cardiomyopathy Questionnaire (KCCQ) have not been defined for patients with heart failure and preserved ejection fraction (HFpEF). The aim of this study was to estimate meaningful thresholds for improvement or worsening in the KCCQ-Physical Limit...
Background: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) compared an initial invasive treatment strategy (INV) with an initial conservative strategy (CON) in 5,179 participants with chronic coronary disease (CCD) and moderate or severe ischemia. The ISCHEMIA research program included a...
Background
EDTA is an intravenous chelating agent with high affinity to divalent cations (lead, cadmium, and calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). Although a large randomized clinical trial showed benefit, smaller studies were inconsistent. We conducted a systematic review of published studies to examine...
Aims:
Coronary artery disease (CAD) portends worse outcomes in heart failure (HF). We aimed to characterize patients with CAD and worsening HF with reduced ejection fraction (HFrEF) and evaluate post hoc whether vericiguat's treatment effect varied according to CAD.
Methods and results:
Cox proportional hazards were generated for the primary end...
Background
For patients hospitalized for heart failure with reduced ejection fraction (HFrEF), guidelines recommend optimization of medical therapy prior to discharge. The degree to which changes in medical therapy occur during hospitalizations for HFrEF in North American clinical practice is unclear.
Methods
The VICTORIA registry enrolled patient...
Background: The Surgical Treatment for Ischemic Heart Failure Trial (STICH) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the econ...
Introduction: Black patients have a higher incidence of heart failure (HF) and worse outcomes than white patients. Guidelines recommend palliative care for patients with advanced HF, but no studies have examined outcomes in a black patient cohort. Methods: This is a post hoc analysis of the Palliative Care in Heart Failure trial, which randomized p...
Background
Although safety and tolerability of vericiguat were established in the VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial in patients with heart failure with reduced ejection fraction, some subgroups may be more susceptible to symptomatic hypotension, such as older patients, those with...
Importance:
The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population.
Objective:
To compare treatment with sacubitril/valsartan treatment with valsartan in patients wi...
Background:
Palliative care (PC) in advanced heart failure (HF) aims to improve symptoms and quality of life (QOL), in part through medication management. The impact of PC on polypharmacy (>5 medications) remains unknown.
Methods and results:
We explored patterns of polypharmacy in the Palliative Care in HF (PAL-HF) randomized controlled trial o...
In Reply Dr Chen and colleagues raise important questions regarding the interpretation of the data published by the CleanUP-IPF investigative group.¹ Two specific points require additional discussion.
Objective: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW).
Design: Multicenter, 1:1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial.
Setting: 34 clinical centers in the United States.
Participants: 1360 HCW at risk for COVID-19 inf...
Background:
The 21st Century Cures Act allows the US Food and Drug Administration (FDA) to utilize real-world data (RWD) to create real-world evidence (RWE) for new indications or post approval study requirements. We compared central adjudication with two insurance claims data sources to understand how endpoint accuracy differences impact RWE resu...
Background
Prior studies suggest similar long-term mortality between patients with heart failure (HF) with preserved (HFpEF) and reduced ejection fraction (HFrEF). However, while coronary heart disease (CHD) is associated with worse prognosis in HF, clinical outcomes are less well characterized for HF without CHD. We investigated the characteristic...
Background:
Prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VICTORIA trial included high-risk patients with HF and reduced ejection fraction and a recent worsening HF event. The study participants had an unusually high event rate despite...
Aims
Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73m². We evaluated the relationship between the efficacy of vericiguat and b...
Importance
Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis.
Objective
To assess the effect of antimicrobial therapy on clinical outcomes.
Design, Setting, and Participants
Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years we...
Randomized clinical trials are the foundation of evidence-based medicine and central to practice guidelines and patient care decisions. Nonetheless, randomized trials in heart failure (HF) populations have become increasingly difficult to conduct and are frequently associated with slow patient enrollment, highly selected populations, extensive data...
Background
In VICTORIA, vericiguat was more effective than placebo in addition to standard of care in reducing the composite outcome of CV death (CVD) or HF hospitalization (HFH). We describe baseline guideline-directed medical therapy (GDMT) and examine if the primary outcome was associated with differences in adherence to GDMT including dosing....
Introduction: The VICTORIA (Vericiguat Global Study in Subjects with HF with Reduced EF) trial included 5050 patients in 3 discrete subgroups reflecting their index worsening heart failure (HF) event: <3 months after HF hospitalization (HFH) (n=3366), 3-6 months after HFH (n=871), and those requiring IV diuretic therapy without HFH within the prior...
Importance
The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.
Objective
To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With He...
Importance
Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life.
Objective
To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Qu...
Background
In VICTORIA vericiguat was more effective than placebo in addition to standard of care in reducing the composite outcome of CV death (CVD) or HF hospitalization (HFH). We describe baseline guideline-directed medical therapy (GDMT) and examine if the primary outcome was associated with differences in adherence to GDMT including dosing.
M...
Machine learning and artificial intelligence are generating significant attention in the scientific community and media. Such algorithms have great potential in medicine for personalizing and improving patient care, including in the diagnosis and management of heart failure. Many physicians are familiar with these terms and the excitement surroundi...
Background
The SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) randomized 2,521 patients with moderate heart failure (HF) to amiodarone, placebo drug, or implantable cardioverter-defibrillator (ICD) therapy. Original trial follow-up ended October 31, 2003. Over a median 45.5-month follow-up, amiodarone, compared with placebo, did not affect...
Background
Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor, apixaban compared with warfarin in high-risk populations incl...
Background:
Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown.
Methods and results:
The ARTEMIS trial (Affordability and Real-World Antipla...