Stuart J Pocock

London School of Hygiene and Tropical Medicine | LSHTM

Background: The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate...

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and...

Background: Biomarker-driven prognostic models incorporating NT-proBNP and hs-cTnT in HFpEF are lacking. Aims: To generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved. Methods: Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or car...

BACKGROUND Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied. OBJECTIVES The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved...

Background: Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated. Methods: Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empa...

Background: Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores...

Background Sodium glucose co-transporter 2 inhibitors (SGLT2i) may induce an early post-initiation eGFR decrease which does not impact the SGLT2i benefits. The occurrence, characteristics, determinants, and clinical significance of an initial eGFR change among patients with heart failure with reduced ejection fraction (HFrEF) require further study....

Aims: Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen heart failure prognosis. Some studies suggested that sodium-glucose cotransporter 2 inhibitors reduce hyperkalaemia, an effect that may have important clinical implications. This analysis evaluates the effect of empagliflozin on...

Background N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure with preserved ejection fraction (HFpEF). Objectives We evaluated associations between both biomarkers and clinical outcomes in the Empagliflozin Outc...

Aims: To report data from EMPEROR-Preserved according to prespecified endpoints of DELIVER. Methods and results: To assess the impact of DELIVER-like definition on EMPEROR-Preserved outcomes, the following differences were reconciled: 1) primary outcome in DELIVER added urgent HF visits to cardiovascular death or HF hospitalizations; 2) EMPEROR-...

Patients with chronic or worsening heart failure (HF) are at a high risk for morbidity, mortality and impaired health related quality of life (HRQoL). This risk is present in the short-term and increases significantly once hospitalized. Thus, it is crucial that HF therapies not only improve outcomes, but do so early post -initiation. The recent EMP...

Background Anemia is frequent among patients with heart failure and reduced ejection fraction (HFrEF) and is associated with poor outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) increase hematocrit and may correct anemia. Aims To study the impact of empagliflozin on hematocrit and anemia, and whether anemia influenced the effect of e...

Aims No therapy has shown to reduce the risk of hospitalization for heart failure across the entire range of ejection fractions seen in clinical practice. We assessed the influence of ejection fraction on the effect of the sodium–glucose cotransporter 2 inhibitor empagliflozin on heart failure outcomes. Methods and results A pooled analysis was...

Resumen Introducción y objetivos Los resultados combinados se utilizan ampliamente, pero tienen diversas limitaciones. El modelo Clinical outcomes, healthcare resource utilization and related costs (COHERENT) es una aproximación nueva para presentar y comparar visualmente todos los componentes de los resultados combinados (incidencia, tiempo, dura...

Objective Atrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF. Methods/results The prospective,...

Background: Patients with heart failure and preserved ejection fraction (HFpEF) have significant impairment in health-related quality of life (HRQoL). In EMPEROR-Preserved, we evaluated the efficacy of empagliflozin on HRQoL in patients with HFpEF and whether the clinical benefit observed with empagliflozin varies according to baseline health statu...

Aim Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to...

Background Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. Methods TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1...

Background It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations...

BACKGROUND: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events.

Background Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them. Methods Chief investigators of vascular prevention randomised controlled trials that show...

Introduction and objectives Composite endpoints are widely used but have several limitations. The Clinical Outcomes, HEalthcare REsource utilizatioN and relaTed costs (COHERENT) model is a new approach for visually displaying and comparing composite endpoints including all their components (incidence, timing, duration) and related costs. We aimed t...

Background: The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported. Objectives: The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outco...

Background: Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with reduced ejection fraction. Its interplay with systolic blood pressure (SBP) is not known. Objectives: The goal of this study was to evaluate the interplay of SBP and the effects of empagliflozin in EMPEROR-Reduced (Empagliflo...

Background: Observational and small randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. Methods: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infa...

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events. Methods: We randomly assigned 5988 patients with class II-IV heart failure with an...

In a planned pooled analysis of two trials that evaluated empagliflozin in patients with heart failure, major adverse renal outcomes occurred in 2.8% of the patients who received empagliflozin and in 3.5% of those who received placebo. Results differed between the two trials.

Background Sodium–glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. Methods In this double-blind trial, we randomly assigned 5988 patients with class...

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events. Methods: We randomly assigned 5988 patients with class II-IV heart failure with an...

Background: In the TWILIGHT trial, ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) was shown to be a safe bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Aims: To evaluate the effects of ticagrelor monotherapy after 3-month DAPT i...

Aims The aim of this study was to generate a biomarker-driven prognostic tool for patients with chronic HFrEF. Circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) each have a marked positive relationship with adverse outcomes in heart failure with reduced ejection fraction (H...

Consensus as to best practices for the selection, reporting, and interpretation of primary and secondary outcomes of randomized controlled trials is lacking. We reviewed the strategies adopted in publications of randomized controlled trials (RCTs) for the analysis, presentation, and interpretation of efficacy outcomes from a survey of all cardiovas...

Aims: To explore the influence of region and race/ethnicity on the effects of empagliflozin in the EMPEROR-Reduced trial. Methods & Results: Of 3730 patients, 1353 (36.3%) were enrolled in Europe, 1286 (34.5%) in Latin America, 425 (11.4%) in North America, and 493 (13.2%) in Asia; 2629 (70.5%) were White, 257 (6.9%) Black, and 672 (18.0%) Asian....

Background: The identification of bleeding risk factors in patients undergoing percutaneous coronary intervention (PCI) is essential to inform subsequent management. Whether clinical presentation per se affects bleeding risk after PCI remains unclear. Aims: We aimed to assess whether clinical presentation per se predisposes to bleeding in patien...

Background Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, inc...

Background Circulating troponin is an important measure of risk in patients with heart failure, but it has not been used to determine if disease severity influences the responses to drug treatments in randomized controlled trials. Methods In the EMPEROR-Reduced trial, patients with class II-IV heart failure and a reduced ejection fraction were ran...

Background: Uncontrolled blood pressure (BP) increases the risk of major adverse cardiovascular events. In SPRINT an intensive versus standard BP lowering strategy resulted in a lower rate of cardiovascular events and death. Whether BP reduction only or also the choice of anti-hypertensive drugs is associated with outcomes remains to be elucidated...

Background Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention. Objectives This study sought to evaluate the effects of the SGLT2 inhibitor emp...

Background Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction. Objectives This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patient...

Background Information is lacking on long-term management of patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2).Objectives Our objectives were to describe antithrombotic management patterns and outcomes in patients with ACS with varying renal function from t...

Aims We evaluated the influence of sacubitril/valsartan on the effects of sodium-glucose cotransporter 2 (SGLT2) inhibition with empagliflozin in patients with heart failure and a reduced ejection fraction. Methods and results The EMPEROR-Reduced trial randomized 3730 patients with heart failure and an ejection fraction ≤40% to placebo or empaglif...

Aims In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction. Methods and results Health status was assessed by the Kansas City Cardiomy...

Background: Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health-related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post-myocardial infarction (MI) patients with and without DM. Hypothesis: In post-MI patients, DM is associated with worse HRQoL, incr...

This review article aims to explain the important issues that data safety monitoring boards (DSMB) face when considering early termination of a trial and is specifically addressed to the needs of clinical and research cardiologists. We give an insight into the overall background and then focus on the three principal reasons for stopping trials, i.e...

Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a study of 8,179 randomized statin-treated patients with elevated triglycerides (TG) and increased cardiovascular (CV) risk followed for a median of 4.9 years, demonstrated robust results. Icosapent ethyl (IPE), a pure and stable prescription form of...

Objectives To describe long-term antithrombotic management patterns (AMPs) in medically managed Asian patients with non-ST-segment myocardial infarction (NSTEMI) or unstable angina (UA). Background Current guidelines support an early invasive strategy in NSTEMI and UA patients, but many are medically managed, and data are limited on long-term AMPs...

Background: In EMPEROR-Reduced, empagliflozin reduced cardiovascular death or HF hospitalization, total HF hospitalizations, and slowed the progressive decline in kidney function in patients with HF and a reduced ejection fraction (HFrEF), with and without diabetes. We aim to study the effect of empagliflozin on cardiovascular and kidney outcomes a...

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly as...

OBJECTIVES This study compared ways of describing treatment effects. The objective was to better explain to clinicians and patients what they might expect from a given treatment, not only in terms of relative and absolute risk reduction, but also in projections of long-term survival. BACKGROUND The restricted mean survival time (RMST) can be used t...

Background: Varying definitions of procedural myocardial infarction (PMI) are in widespread use. Objectives: This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass gra...

Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of t...

The win ratio was introduced in 2012 as a new method for examining composite endpoints and has since been widely adopted in cardiovascular (CV) trials. Improving upon conventional methods for analysing composite endpoints, the win ratio accounts for relative priorities of the components and allows the components to be different types of outcomes. F...

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fract...

Aims: To model the safety and effectiveness of drug-coated stents (DCS) vs. bare-metal stents (BMS) in high bleeding risk (HBR) patients according to the Academic Research Criteria (ARC) criteria. Methods and results: Participants from the LEADERS FREE (LF) and LEADERS FREE (LFII) studies were pooled into one dataset. Participants were treated w...

Background Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. H...

Background Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real‐world AMPs up to 2 years post discharge for A...

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infectio...

Healthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or c...

Objective: The LEADER trial (ClinicalTrials.gov reg. no. NCT01179048) demonstrated a reduced risk of cardiovascular (CV) events for patients with type 2 diabetes who received the glucagon-like peptide 1 receptor agonist liraglutide versus placebo. The mechanisms behind this CV benefit remain unclear. We aimed to identify potential mediators for th...

Aims More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). Methods and results Between 2008–2017, using the Optum longitudinal database, a patient‐level database that integrates multiple US‐based electronic health and claim records from several health care provid...

Aims Approximately half of cases of cardiovascular disease (CVD) worldwide occur in Asia, with acute coronary syndrome (ACS) a leading cause of mortality. Long-term ACS-related outcomes data in Asia are limited. This analysis examined 2-year ACS-related outcomes in patients enrolled in the EPICOR Asia study, and the association between patient char...

Background Spironolactone up‐titration may be limited by side effects that could be minimized at lower than target doses, whether lower than target doses remain efficacious is unknown. In TOPCAT, spironolactone (or placebo) were started at 15 mg/day, and increased up to a maximum of 45 mg/day. The prognostic implications related to spironolactone d...

Background Cardiovascular diseases account for approximately half of all deaths in Asia. The present analysis aimed to evaluate characteristics, antithrombotic management patterns (AMPs), and outcomes in patients with acute coronary syndrome (ACS) who underwent in-hospital percutaneous coronary intervention (PCI) and survived to hospital discharge,...

Aims: Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular eject...

Background: The majority of stent-related major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are believed to occur within the first year. Very-late (>1-year) stent-related MACE have not been well described. Objectives: The purpose of this study was to assess the frequency and predictors of very-late stent-r...

Background: Evidence is lacking on long-term outcomes in unselected patients surviving the first year following myocardial infarction (MI). Methods and results: The TIGRIS (long-Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post-myocardial infarction patients) prospective registry enrolle...

Aim Patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) remain at high risk of cardiovascular events despite the use of contemporary drug-eluting stents (DES). This trial aim to compare the clinical efficacy of 2 novel second-generation DES in patients with DM. Methods and results The Second-Generation Drug-Elu...

Background: Patients with non-ST-segment elevation myocardial infarction (NSTEMI) have a generally poor prognosis and antithrombotic management patterns (AMPs) used post-acute coronary syndrome (ACS) remain unclear. Duration of dual antiplatelet therapy (DAPT) and patient characteristics was evaluated in NSTEMI patients enrolled in EPICOR Asia. H...