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Showing papers by "Eugene Braunwald published in 2019"


Journal ArticleDOI
TL;DR: Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril–valsartan therapy led to a greater reduction in the N‐terminal pro–B‐type natriuretic peptide concentration than enalapril therapy.
Abstract: Background Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril–valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. Methods We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. Results Of the 881 patients wh...

760 citations


Journal ArticleDOI
Jane Armitage, Colin Baigent, Elizabeth H Barnes, D. John Betteridge, Lisa Blackwell, Michael A. Blazing, Louise Bowman, Eugene Braunwald, Robert P Byington, Christopher P. Cannon, Michael Clearfield, Helen M. Colhoun, Rory Collins, Björn Dahlöf, Kelly Davies, Barry R. Davis, James A. de Lemos, John R. Downs, Paul N. Durrington, Jonathan Emberson, Bengt Fellström, Marcus Flather, Ian Ford, Maria Grazia Franzosi, Jordan Fulcher, John H. Fuller, Curt D. Furberg, David L. Gordon, Shinya Goto, Antonio M. Gotto, Heather Halls, Charlie H.S. Harper, C. Morton Hawkins, William G. Herrington, Graham A. Hitman, Hallvard Holdaas, Lisa Holland, Alan G. Jardine, J. Wouter Jukema, John J.P. Kastelein, Sharon Kean, Anthony C Keech, Adrienne Kirby, John Kjekshus, Genell L. Knatterud, Robert H. Knopp, Wolfgang Koenig, Michael J. Koren, Vera Krane, Martin J Landray, John C. LaRosa, Eva Lonn, Peter W. Macfarlane, Stephen MacMahon, Aldo P. Maggioni, Roberto Marchioli, Ian C. Marschner, Borislava Mihaylova, Lemuel A. Moyé, Sabina A. Murphy, Haruo Nakamura, Andrew Neil, Connie B. Newman, Rachel O'Connell, Chris J. Packard, Sarah Parish, Terje R. Pedersen, Richard Peto, Marc A. Pfeffer, Neil Poulter, David Preiss, Christina Reith, Paul M. Ridker, Michele Robertson, Frank M. Sacks, Naveed Sattar, Roland E. Schmieder, Patrick W. Serruys, Peter S. Sever, John Shaw, Charles L. Shear, John Simes, Peter Sleight, Enti Spata, Luigi Tavazzi, Jonathan A. Tobert, Gianni Tognoni, Andrew Tonkin, Stella Trompet, John Varigos, Christoph Wanner, Hans Wedel, Harvey D. White, John Wikstrand, Lars Wilhelmsen, Kate Wilson, R. Young, Salim Yusuf, Faiez Zannad 
TL;DR: A meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages observed a significant reduction in major vascular events in all age groups.

454 citations


Journal ArticleDOI
TL;DR: The important interactions between T2DM, heart failure, and renal dysfunction, forming vicious circles are described, and the interruption of these circles represent important therapeutic goals.

134 citations


Journal ArticleDOI
TL;DR: The primary results of the randomized double-blind PIONEER-HF trial were reported demonstrating that, in comparison with enalapril, in patients hemodynamically stabilized during hospitalization for ADHF, sacubitril/ valsartan achieved a greater reduction in N-terminal pro-brain natriuretic peptide concentration, was safe and well-tolerated.
Abstract: Sources of Funding, see page xxx In outpatients with chronic heart failure (HF) with reduced ejection fraction known to tolerate an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, substitution of the angiotensin-neprilysin inhibitor sacubitril/valsartan reduces the rate of cardiovascular death or HF hospitalization.1 Accordingly, consensus guidelines recommend the use of sacubitril/valsartan to treat patients with symptomatic HF with reduced ejection fraction.2 Until recently, however, the efficacy and safety of sacubitril/valsartan among patients hospitalized for acute decompensated heart failure (ADHF) was unknown. We have reported the primary results of the randomized double-blind PIONEER-HF trial (Comparison of SacubitrilValsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) demonstrating that, in comparison with enalapril, in patients hemodynamically stabilized during hospitalization for ADHF, sacubitril/ valsartan achieved a greater reduction in N-terminal pro-brain natriuretic peptide concentration, was safe and well-tolerated, and was associated with a significant reduction in the serious composite clinical end point of death, rehospitalization for HF, implantation of a left ventricular assist device, or listing for cardiac transplantation (hazard ratio, 0.54; 95% CI, 0.37–0.79).3 By design,4 our previously reported analyses of clinical end points relied on investigator-reported data. We undertook an exploratory analysis of the end point of cardiovascular death or rehospitalization for HF to assess the consistency with the results of the pivotal trial in chronic HF.1 A post hoc adjudication of rehospitalization for HF and cause of death according to standardized definitions1,5 was performed by the same blinded clinical events committee (CEC) for rigorous confirmation of these end points. In this research letter, we report the results of these additional analyses from PIONEER-HF. PIONEER-HF was an 8-week multicenter, randomized, double-blind, doubledummy, active-controlled trial of in-hospital initiation of sacubitril/valsartan in comparison with enalapril in patients stabilized during hospitalization for ADHF.4 Eligible patients were to have a left ventricular ejection fraction ≤40% and signs and symptoms of HF along with an N-terminal pro-brain natriuretic peptide concentration ≥1600 pg/mL or brain natriuretic peptide concentration ≥400 pg/mL. Patients were enrolled ≥24 hours and up to 10 days after presentation while still hospitalized and were to be hemodynamically stable using protocol-defined criteria.4 Institutional review boards approved the protocol at all sites. All participants provided written informed consent. We evaluated the cumulative incidence of the adjudicated prespecified exploratory clinical composite end point of death from any cause, rehospitalization for HF, left ventricular assist device implantation, or listing for cardiac transplant, and the composite of cardiovascular death or rehospitalization for HF, as well. Adjudication of death and rehospitalization for HF was performed by a CEC blinded to David A. Morrow, MD, MPH Eric J. Velazquez, MD Adam D. DeVore, MD, MHS Akshay S. Desai, MD, MPH Carol I. Duffy, DO Andrew P. Ambrosy, MD Yared Gurmu, PhD Kevin McCague, MA Ricardo Rocha, MD Eugene Braunwald, MD

111 citations


Journal ArticleDOI
TL;DR: The ABC-stroke and ABC-bleeding scores evaluated in this anticoagulated clinical trial cohort were well calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively, and may help identify patients most likely to derive a benefit from treatment with non–vitamin K antagonist oral antICOagulants.
Abstract: Background: The ABC (age, biomarker, clinical history)-stroke and ABC-bleeding risk scores incorporate clinical variables and cardiovascular biomarkers to estimate risk of stroke or systemic emboli...

91 citations


Journal ArticleDOI
TL;DR: Patients with type 2 diabetes mellitus are at increased risk of developing heart failure and Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure.
Abstract: Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart f...

88 citations


Journal ArticleDOI
TL;DR: An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding, and time in therapeutic range for warfarin improved significantly as BMI increased.
Abstract: Aims To investigate the relationship between body mass index (BMI) and outcomes in patients with atrial fibrillation (AF). Methods and results In the ENGAGE AF-TIMI 48 trial, patients with AF were randomized to warfarin (international normalized ratio 2.0-3.0) or edoxaban. The cohort (N = 21 028) included patients across BMI categories (kg/m2): underweight ( 18.5 kg/m2, while time in therapeutic range for warfarin improved significantly as BMI increased (P Conclusion An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding. The efficacy and safety profiles of edoxaban were similar across BMI categories ranging from 18.5 to >40.

82 citations


Journal ArticleDOI
TL;DR: In IMPROVE-IT, patients hospitalized for ACS derived benefit from higher-intensity therapy to lower lipid levels with simvastatin-ezetimibe compared with simVastatin monotherapy, with the greatest absolute risk reduction among patients 75 years or older.
Abstract: Importance Limited evidence is available regarding the benefit and hazard of higher-intensity treatment to lower lipid levels among patients 75 years or older. As a result, guideline recommendations differ for this age group compared with younger patients. Objective To determine the effect on outcomes and risks of combination ezetimibe and simvastatin compared with simvastatin monotherapy to lower lipid levels among patients 75 years or older with stabilized acute coronary syndrome (ACS). Design, Setting, Participants In this prespecified secondary analysis of the global, multicenter, prospective clinical randomized Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), outcomes and risks were compared by age among patients 50 years or older after a hospitalization for ACS. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed May 29, 2015, through March 13, 2018, using Kaplan-Meier curves and Cox proportional hazards models. Interventions Double-blind randomized assignment to combined simvastatin and ezetimibe or simvastatin and placebo with follow-up for a median of 6 years (interquartile range, 4.3-7.1 years). Main Outcomes and Measures The primary composite end point consisted of death due to cardiovascular disease, myocardial infarction (MI), stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days. Individual adverse ischemic and safety end points and lipid variables were also analyzed. Results Of 18 144 patients enrolled (13 728 men [75.7%]; mean [SD] age, 64.1 [9.8] years), 5173 (28.5%) were 65 to 74 years old, and 2798 (15.4%) were 75 years or older at randomization. Treatment with simvastatin-ezetimibe resulted in lower rates of the primary end point than simvastatin-placebo, including 0.9% for patients younger than 65 years (HR, 0.97; 95% CI, 0.90-1.05) and 0.8% for patients 65 to 74 years of age (hazard ratio [HR], 0.96; 95% CI, 0.87-1.06), with the greatest absolute risk reduction of 8.7% for patients 75 years or older (HR, 0.80; 95% CI, 0.70-0.90) (P = .02 for interaction). The rate of adverse events did not increase with simvastatin-ezetimibe vs simvastatin-placebo among younger or older patients. Conclusions and Relevance In IMPROVE-IT, patients hospitalized for ACS derived benefit from higher-intensity therapy to lower lipid levels with simvastatin-ezetimibe compared with simvastatin monotherapy, with the greatest absolute risk reduction among patients 75 years or older. Addition of ezetimibe to simvastatin was not associated with any significant increase in safety issues among older patients. These results may have implications for guideline recommendations regarding lowering of lipid levels in the elderly. Trial Registration ClinicalTrials.gov identifier:NCT00202878

73 citations


Journal ArticleDOI
TL;DR: In a cohort of 12,156 patients with T2DM and high CV risk, metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but notLower rates of the composite endpoint of CV death, MI, or ischemic stroke.
Abstract: Background: Metformin is first-line therapy for type 2 diabetes mellitus, although its effects on the cardiovascular system are unproved. Methods: In this post hoc analysis, patients in SAVOR-TIMI ...

58 citations


Journal ArticleDOI
TL;DR: Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edxaban concentration and anti-FXa activity achieved in patients of Asian race.
Abstract: Aims Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races. Methods and results There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively). Conclusion Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.

54 citations


Journal ArticleDOI
TL;DR: Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1–4 weeks.
Abstract: AIMS Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3'5' monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). METHODS AND RESULTS PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome. CONCLUSION Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1-4 weeks. CLINICAL TRIALS REGISTRATION NCT02554890 clinical.trials.gov.

Journal ArticleDOI
TL;DR: After accounting for cardiovascular risk factors, women enrolled in clinical trials were at lower risk of MACE than men after NSTEACS, however, women remain undertreated with many evidence-based therapies.

Journal ArticleDOI
TL;DR: The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular death or heart failure hospitalization in a population with atrial fibrillation.
Abstract: Aims The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular (CV) death or heart failure (HF) hospitalization in a population with atrial fibrillation (AF). Methods and results In a prospective echocardiographic substudy of the Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study, 971 patients underwent transthoracic echocardiography. The associations between LA structure (LA volume index [LAVi]) and function (LA emptying fraction [LAEF] and LA expansion index [LAEi]) and risk for the composite endpoint of CV death or HF hospitalization, and its components, were assessed. Over a median follow-up of 2.5 years, 142 patients (14.6%) experienced CV death or HF hospitalization. Higher LAVi and lower LAEF and LAEi were each associated with a higher unadjusted risk for the composite outcome and its components. After adjustment for clinical and echocardiographic confounders, only measures of impaired LA function were predictive of the composite outcome (hazard ratio [HR] per 1 standard deviation [SD] decrease in LAEF: 1.35; 95% confidence interval [CI] 1.09-1.67 [P = 0.005]; HR per 1 SD decrease in LAEi: 1.34; 95% CI 1.06-1.69 [P = 0.012]). These findings were similar regardless of left ventricular ejection fraction, history of HF or whether patients were in AF or sinus rhythm at the time of the echocardiographic examination. Conclusions In patients with AF, LA dysfunction was significantly associated with an increased risk for CV death or HF hospitalization and was more predictive of these outcomes than LA size. These parameters may help to identify AF patients at greatest risk for the development of HF. Clinical trial registration ClinicalTrials.gov, NCT00781391.

Journal ArticleDOI
TL;DR: Limited data exist on the prognostic value of Klotho and FGF‐23 levels in combination or their ability to predict benefit from angiotensin‐converting enzyme (ACE) inhibition.
Abstract: AIMS Klotho, an essential co-receptor for fibroblast growth factor (FGF)-23, has potentially beneficial inhibitory effects on the renin-angiotensin system. Limited data exist on the prognostic value of Klotho and FGF-23 levels in combination or their ability to predict benefit from angiotensin-converting enzyme (ACE) inhibition. METHODS AND RESULTS A total of 3555 patients with stable ischaemic heart disease and left ventricular ejection fraction > 40% enrolled in the PEACE trial of trandolapril vs. placebo had Klotho levels drawn at randomization. Patients were characterized by quartiles of Klotho and FGF-23 concentrations. Six-year Kaplan-Meier rates and adjusted risk were calculated in the placebo arm for the composite of cardiovascular (CV) death or hospitalization for heart failure and its components. Low [quartile (Q) 1-3] Klotho concentration was associated with an increased rate of CV death or hospitalization for heart failure as compared with Q4 (8.2% vs. 4.2%; P = 0.03). After multivariable adjustment for clinical variables and renal and CV biomarkers (estimated glomerular filtration rate, cystatin-C, urine albumin-to-creatinine ratio, FGF-23, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein), low Klotho concentration remained strongly associated with increased risk of CV death or hospitalization for heart failure [adjusted hazard ratio (HR) 2.62; 95% confidence interval (CI) 1.35-5.08; P < 0.01]. The combination of low Klotho and high (Q4) FGF-23 concentration identified patients at particularly elevated risk (adjusted HR 3.99; 95% CI 1.67-9.56; P < 0.01). This high-risk combination additionally predicted benefit from trandolapril (HR 0.39; 95% CI 0.23-0.68; Pinteraction < 0.01). CONCLUSIONS Low Klotho concentration is associated with an increased risk of CV death or heart failure hospitalization in patients with stable ischaemic heart disease. The combination of low Klotho and high FGF-23 further identifies patients at distinctly elevated risk who derive clinical benefit from the ACE-inhibitor trandolapril.

Journal ArticleDOI
TL;DR: In a randomized trial of patients with heart failure and reduced ejection fraction, the SGLT2 inhibitor dapagliflozin markedly reduced mortality and worsening heart failure.

Journal ArticleDOI
TL;DR: There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population of stable patients with a prior myocardial infarction and a relative risk reduction of 20% in CV death, MI, or stroke.
Abstract: Aims In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15–16% in stable patients with a prior myocardial infarction (MI) 1–3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment. Methods and results Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan–Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70–0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67–0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65–3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68–2.01; P = 0.58). Conclusion In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population. Clinical trial registration http://www.clinicaltrials.gov NCT01225562

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TL;DR: Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease, and a history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin.

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TL;DR: A biomarker-based strategy identifies a gradient of risk among patients post-ACS, offering the potential to identify higher-risk patients with a correspondingly high absolute benefit from the addition of ezetimibe to statin therapy.

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TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus as a source of infection for other animals.
Abstract: Background: Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by ADCY9 geno...

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TL;DR: In patients with confirmed atherosclerosis enrolled in SAVOR-TIMI 53, 11% had polyvascular disease; and compared with diabetic patients with single bed disease, the risk of ischemic events and overall mortality was substantially higher in patients with T2DM and polyv vascular disease.
Abstract: We sought to assess the prevalence of polyvascular disease in patients with type 2 diabetes mellitus (T2DM) and its impact on ischemic events. Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53, a large contemporary, randomized trial, evaluated the effect of saxagliptin versus placebo in 16,492 patients with T2DM and a history of or at risk for cardiovascular (CV) events. Polyvascular disease was defined as a history of clinical events involving 2 or more vascular beds (coronary, peripheral, or cerebrovascular system) at the time of randomization. The primary composite endpoint of CV death, myocardial infarction, or ischemic stroke was compared according to the number of diseased arterial beds. At the time of randomization, 3,667 (22.2%) patients had risk factors for CV events; 11,423 (69.3%) had established 1 arterial bed disease; 1,298 (7.9%) had 2 bed disease; and 104 (0.6%) had 3 bed disease. Compared with diabetic patients with no established atherosclerosis, the adjusted hazard ratio for the composite primary end point in 1, 2, or 3 diseased beds was 1.95, 3.54, and 4.64, respectively (trend p < 0.0001). The adjusted risk for overall mortality increased in a similar stepwise fashion from 1.47 to 2.33 to 3.12, respectively (trend p = 0.0001) with each additional diseased arterial territory. In conclusion, in patients with confirmed atherosclerosis enrolled in SAVOR-TIMI 53, 11% had polyvascular disease; and compared with diabetic patients with single bed disease, the risk of ischemic events and overall mortality was substantially higher in patients with T2DM and polyvascular disease.

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TL;DR: Smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates, and was highest in the United States (7-year KM rate 57.4%) and in multivariable modeling.
Abstract: Background: Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been sys...

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TL;DR: The reduction in ischemic events with the higher-dose edoxaban regimen versus warfarin was greater in patients with CAD, while bleeding was significantly reduced with edoxaba regardless of CAD status.
Abstract: Background:The relative efficacy and safety profile of the oral Factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation and established coronary artery disease (CAD...

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TL;DR: There was an approximately four-fold difference in the frequency of the most severe bleeding events across commonly used bleeding scales among patients with AF at risk for stroke, and the relative safety of edoxaban as compared with warfarin tended to increase with greater severity of bleeding.
Abstract: Background: Numerous scales exist for the classification of major bleeding events. Limited data compare the most commonly used bleeding scales within a single at-risk cohort of patients with atrial...

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TL;DR: Biomarker-positive patients with no prior history of stroke or transient ischemic attack may be a optimal target population to receive “dual pathway” therapy with rivaroxaban plus dual antiplatelet therapy for secondary prevention following ACS.
Abstract: Background:Despite dual antiplatelet therapy, persistent thrombin generation and thrombin-mediated platelet activation account in part for the residual risk of atherothrombotic disease among patien...

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TL;DR: Hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM.
Abstract: BACKGROUND: Cardiac and renal diseases commonly occur with bidirectional interactions. We hypothesized that cardiac and inflammatory biomarkers may assist in identification of patients with type 2 diabetes mellitus (T2DM) at high risk of worsening renal function. METHODS: In this exploratory analysis from SAVOR-TIMI 53, concentrations of high-sensitivity cardiac troponin T (hs-TnT), N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) were measured in baseline serum samples of 12310 patients. The primary end point for this analysis was a ≥40% decrease in estimated glomerular filtration rate (eGFR) at end of treatment (EOT) at a median of 2.1 years. The relationships between biomarkers and the end point were modeled using adjusted logistic and Cox regression. RESULTS: After multivariable adjustment including baseline renal function, each biomarker was independently associated with an increased risk of ≥40% decrease in eGFR at EOT [Quartile (Q) Q4 vs Q1: hs-TnT adjusted odds ratio (OR), 5.63 (3.49–9.10); NT-proBNP adjusted OR, 3.53 (2.29–5.45); hs-CRP adjusted OR, 1.84 (95% CI, 1.27–2.68); all P values ≤0.001]. Furthermore, each biomarker was independently associated with higher risk of worsening of urinary albumin-to-creatinine ratio (UACR) category (all P values ≤0.002). Sensitivity analyses in patients without heart failure and eGFR >60 mL/min provided similar results. In an adjusted multimarker model, hs-TnT and NT-proBNP remained significantly associated with both renal outcomes (all P values CONCLUSIONS: hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM. Patients with high cardiac or inflammatory biomarkers should be treated not only for their risk of cardiovascular outcomes but also followed for renal deterioration.

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TL;DR: The efficacy and safety of Edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP, which is a risk factor for stroke and bleeding in patients with atrial fibrillation.
Abstract: Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of dire...

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TL;DR: The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM.
Abstract: Background: The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertro...

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TL;DR: Levels of beta‐CTx, a biomarker of collagen turnover, were associated with cardiovascular death and HF in patients with non–ST‐elevation acute coronary syndrome and may provide complementary pathobiological insight and risk stratification in these patients.
Abstract: Background Small studies have suggested an association between markers of collagen turnover and adverse outcomes in heart failure (HF). We examined C‐terminal telopeptide (beta‐CTx) and the risk of...

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01 Feb 2019
TL;DR: Recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure, and one trial also showed a fall in cardiovascular and total death.
Abstract: Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.