1,779 results on '"Eugene Braunwald"'
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2. Cardiovascular Events and Long‐Term Risk of Sudden Death Among Stabilized Patients After Acute Coronary Syndrome: Insights From IMPROVE‐IT
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Christopher B. Fordyce, Robert P. Giugliano, Christopher P. Cannon, Matthew T. Roe, Abhinav Sharma, Courtney Page, Jennifer A. White, Yuliya Lokhnygina, Eugene Braunwald, and Michael A. Blazing
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long‐term outcomes ,myocardial infarction ,sudden death ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Unlike patients with low ejection fraction after an acute coronary syndrome (ACS), little is known about the long‐term incidence and influence of cardiovascular events before sudden death among stabilized patients after ACS. Methods and Results A total of 18 144 patients stabilized within 10 days after ACS in IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) were studied. Cumulative incidence rates (IRs) and IRs per 100 patient‐years of sudden death were calculated. Using Cox proportional hazards, the association of ≥1 additional postrandomization cardiovascular events (myocardial infarction, stroke, and hospitalization for unstable angina or heart failure) with sudden death was examined. Early (≤1 year after ACS) and late sudden deaths (>1 year) were compared. Of 2446 total deaths, 402 (16%) were sudden. The median time to sudden death was 2.7 years, with 109 early and 293 late sudden deaths. The cumulative IR was 2.47% (95% CI, 2.23%–2.73%) at 7 years of follow‐up. The risk of sudden death following a postrandomization cardiovascular event (150/402 [37%] sudden deaths; median 1.4 years) was greater (IR/100 patient‐years, 1.45 [95% CI, 1.23–1.69]) than the risk with no postrandomization cardiovascular event (IR/100 patient‐years, 0.27 [95% CI, 0.24–0.30]). Postrandomization myocardial infarction (hazard ratio [HR], 3.64 [95% CI, 2.85–4.66]) and heart failure (HR, 4.55 [95% CI, 3.33–6.22]) significantly increased future risk of sudden death. Conclusions Patients stabilized within 10 days of an ACS remain at long‐term risk of sudden death with the greatest risk in those with an additional cardiovascular event. These results refine the long‐term risk and risk effectors of sudden death, which may help clinicians identify opportunities to improve care. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.
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- 2022
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3. Prospective Evaluation of Malignancy in 17,708 Patients Randomized to Ezetimibe Versus Placebo
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Robert P. Giugliano, MD, SM, Baris Gencer, MD, Stephen D. Wiviott, MD, Jeong-Gun Park, PHD, Charles S. Fuchs, MD, MPH, Wolfram Goessling, MD, PHD, Thomas A. Musliner, MD, Andrew M. Tershakovec, MD, MPH, Michael A. Blazing, MD, Robert Califf, MD, Christopher P. Cannon, MD, and Eugene Braunwald, MD
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acute coronary syndromes ,cancer ,ezetimibe ,lipid-lowering therapy ,lipids ,malignancy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: An increased risk of malignancy was reported with simvastatin/ezetimibe in 1,873 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial. Objectives: The purpose of this study was to clarify this unexpected finding in a larger sample size of patients stabilized after acute coronary syndrome, we conducted a prospective systematic analysis of malignancy events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Methods: Within IMPROVE-IT, 17,708 patients post–acute coronary syndrome were randomized to either ezetimibe 10 mg or matching placebo on a background of simvastatin 40 mg who took ≥1 dose of the study drug. Suspected tumors (benign and malignant) reported by investigators or identified from a review of adverse events were adjudicated by oncologists without knowledge of drug assignment. The primary malignancy endpoint included new, relapsing, or progressive malignancies (excluding nonmelanotic skin malignancies). The secondary endpoint was death due to malignancy. Results: In this trial, 1,470 patients developed the primary malignancy endpoint during a median 6 years of follow-up. The most common malignancy locations were prostate (18.9%), lung (16.8%), and bladder (8.8%) with no differences by treatment group (p > 0.05 for each location). Kaplan-Meier 7-year rates of malignancies were similar with ezetimibe and placebo (10.2% vs. 10.3%; hazard ratio: 1.03; 95% confidence interval: 0.93 to 1.14; p = 0.56), as were the rates for malignancy death (3.8% vs. 3.6%; hazard ratio: 1.04; 95% confidence interval: 0.88 to 1.23; p = 0.68). Conclusions: Among 17,708 patients receiving simvastatin 40 mg daily, those randomized to ezetimibe 10 mg daily had a similar incidence of malignancy and deaths due to malignancy compared with those receiving placebo during a median follow-up of 6 years (96,377 patient-years). (IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin [Ezetimibe/Simvastatin] vs Simvastatin [P04103]; NCT00202878)
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- 2020
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4. Long‐Term Ticagrelor in Patients With Prior Coronary Stenting in the PEGASUS‐TIMI 54 Trial
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Brian A. Bergmark, Deepak L. Bhatt, P. Gabriel Steg, Andrzej Budaj, Robert F. Storey, Yared Gurmu, Julia F. Kuder, KyungAh Im, Giulia Magnani, Ton Oude Ophuis, Christian Hamm, Jindřich Špinar, Robert G. Kiss, Frans J. Van de Werf, Gilles Montalescot, Per Johanson, Eugene Braunwald, Marc S. Sabatine, and Marc P. Bonaca
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acute coronary syndrome ,antiplatelet therapy ,P2Y12 inhibitor ,PCI ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Coronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long‐term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial. Methods and Results Patients in PEGASUS‐TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug‐eluting stent and first‐ versus later‐generation drug‐eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelorpooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75–96) regardless of stent type (bare metal stent versus drug‐eluting stent: pinteraction=0.767; first versus later generation: pinteraction=0.940). The rate of any stent thrombosis was numerically lower with ticagrelorpooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50–1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90–3.68). Conclusions Long‐term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor. Registration Information clinicaltrials.gov. Identifier: NCT01225562.
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- 2021
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5. Transmethylamine‐N‐Oxide Is Associated With Diffuse Cardiac Fibrosis in People Living With HIV
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Nalini A. Colaco, Teresa S. Wang, Yifei Ma, Rebecca Scherzer, Olga R. Ilkayeva, Patrice Desvigne‐Nickens, Eugene Braunwald, Adrian F. Hernandez, Javed Butler, Svati H. Shah, Sanjiv J. Shah, and Priscilla Y. Hsue
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diastolic dysfunction ,HIV ,myocardial fibrosis ,transmethylamine‐N‐oxide ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background People living with HIV are at increased risk of developing diastolic dysfunction, heart failure, and sudden cardiac death, all of which have been characterized by higher levels of myocardial fibrosis. Transmethylamine‐N‐oxide (TMAO), a dietary gut metabolite, is linked to the development of myocardial fibrosis in animal models. However, it is unclear whether TMAO plays a role in the development of myocardial fibrosis in people living with HIV. Methods and Results The study population consisted of participants enrolled in the multisite cross‐sectional study called CHART‐HIV (Characterizing Heart Function on Anti‐Retroviral Therapy). Participants underwent echocardiography, cardiac magnetic resonance imaging, biomarker analysis, and targeted assessment of gut‐related circulating metabolites; diastolic dysfunction was determined by study‐specific criteria. Multivariable linear regression models were performed to examine the relationship of gut‐related metabolites with serum and imaging measures of myocardial fibrosis. Models were adjusted for traditional cardiovascular, inflammatory, and HIV‐related risk factors. Diastolic dysfunction was present in 94 of 195 individuals (48%) in CHART‐HIV; this cohort demonstrated higher prevalence of hypertension, hyperlipidemia, and chronic kidney disease as well as higher plasma levels of both TMAO and choline. TMAO levels were associated with parameters reflecting increased left ventricular filling pressures and with a marker of the innate immune system. TMAO levels correlated with diffuse myocardial fibrosis (R=0.35; P
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- 2021
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6. Featuring: Eugene Braunwald
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Eugene Braunwald
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
In the Cardiology Masters section of European Cardiology Review, we bring you an insight into the career of a key contributor to the field of cardiology. In this issue, we feature Professor Eugene Braunwald, cardiovascular medicine specialist at Brigham and Women’s Hospital and distinguished Hersey Professor of Medicine at Harvard University, Boston, Massachusetts, US.
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- 2019
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7. Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs
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Thomas A Zelniker and Eugene Braunwald
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - 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.
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- 2019
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8. Predictors, Type, and Impact of Bleeding on the Net Clinical Benefit of Long‐Term Ticagrelor in Stable Patients With Prior Myocardial Infarction
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Giulia Magnani, Diego Ardissino, KyungAh Im, Andrzej Budaj, Robert F. Storey, P. Gabriel Steg, Deepak L. Bhatt, Marc Cohen, Ton Oude Ophius, Assen Goudev, Alexander Parkhomenko, Gabriel Kamensky, Dominick J. Angiolillo, José López‐Sendón, Per Johanson, Eugene Braunwald, Marc S. Sabatine, and Marc P. Bonaca
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benefit‐risk ratio ,bleeding ,long‐term ticagrelor ,myocardial infarction ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Ticagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy. Methods and Results PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis in Myocardial Infarction 54) randomized 21 162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60 mg or 90 mg twice daily or placebo, with ticagrelor 60 mg approved for long‐term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60 mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3‐fold higher rates of bleeding with ticagrelor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%; P=0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65–0.96; P interaction = 0.03). Conclusions In patients with prior myocardial infarction, bleeding with ticagrelor 60 mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor. Registration URL https://www.clinicaltrials.gov/. Unique identifier: NCT01225562.
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- 2021
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9. Biomarker of Collagen Turnover (C‐Terminal Telopeptide) and Prognosis in Patients With Non‐ST‐Elevation Acute Coronary Syndromes
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Thomas A. Zelniker, Petr Jarolim, Benjamin M. Scirica, Eugene Braunwald, Jeong‐Gun Park, Saumya Das, Marc S. Sabatine, and David A. Morrow
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beta‐CTx ,cardiovascular death ,collagen turnover ,C‐terminal telopeptide ,heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - 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 cardiovascular death or new or worsening HF in non–ST‐elevation acute coronary syndrome. Methods and Results We measured baseline serum beta‐CTx, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hsTnT (high‐sensitivity cardiac troponin T) and hsCRP (high‐sensitivity C‐reactive protein) (Roche Diagnostics) in a nested biomarker analysis (n=4094) from a study of patients with non–ST‐elevation acute coronary syndrome. The relationship between quartiles of beta‐CTx and cardiovascular death or HF over a median follow‐up time of 12 months was analyzed using adjusted Cox models. Higher beta‐CTx levels identified a significantly higher risk of cardiovascular death/HF (Q4 10.9% versus Q1 3.8%, Logrank P
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- 2019
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10. Safety and Efficacy of Rivaroxaban When Added to Aspirin Monotherapy Among Stabilized Post‐Acute Coronary Syndrome Patients: A Pooled Analysis Study of ATLAS ACS‐TIMI 46 and ATLAS ACS 2‐TIMI 51
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William J. Gibson, C. Michael Gibson, Megan K. Yee, Serge Korjian, Yazan Daaboul, Alexei N. Plotnikov, Paul Burton, and Eugene Braunwald
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acute coronary syndrome ,anticoagulation ,aspirin ,rivaroxaban ,thrombosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background A residual risk of ischemic events following an acute coronary syndrome (ACS) remains despite antiplatelet therapy. The addition of an antithrombin as part of a “dual pathway” approach may further improve outcomes as thrombin generation persists for several months post‐ACS. The present study evaluates the safety and efficacy of “dual pathway” therapy (rivaroxaban plus aspirin) as compared with aspirin monotherapy among post‐ACS patients. Methods and Results A total of 1477 patients were analyzed in a pooled analysis of subsets of the ATLAS ACS‐TIMI (Anti‐Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome – Thrombolysis in Myocardial Infarction) 46 and ATLAS ACS 2‐TIMI 51 trials including post‐ACS patients receiving aspirin monotherapy and randomized to either rivaroxaban 2.5 mg BID or rivaroxaban 5 mg BID or placebo. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or stroke (ischemic, hemorrhagic, or of uncertain cause). The primary safety end point was TIMI‐non‐coronary artery bypass (CABG) major bleeding. The combined rivaroxaban group (2.5 or 5 mg BID) among stabilized post‐ACS patients on a background of aspirin monotherapy was associated with a significant reduction in the primary end point as compared with placebo (hazard ratio=0.65, 95% CI=0.45–0.92, P=0.016). Although the combined rivaroxaban dose groups were associated with higher rates of non‐CABG TIMI major bleeding, the 2.5 mg dose group was not, and the overall number of patients experiencing a non‐CABG TIMI major bleeding event was low (1.5%). Conclusions Among patients in the immediate post‐ACS period, a “dual pathway” approach using aspirin and low‐dose rivaroxaban may reduce the risk of secondary atherothrombotic events, but increase bleeding risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00402597; NCT00809965.
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- 2019
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11. High‐Sensitivity Troponin I in Hospitalized and Ambulatory Patients With Heart Failure With Preserved Ejection Fraction: Insights From the Heart Failure Clinical Research Network
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Marat Fudim, Andrew P. Ambrosy, Jie‐Lena Sun, Kevin J. Anstrom, Bradley A. Bart, Javed Butler, Omar AbouEzzeddine, Stephen J. Greene, Robert J. Mentz, Margaret M. Redfield, Yogesh N.V. Reddy, Muthiah Vaduganathan, Eugene Braunwald, Adrian F. Hernandez, Barry A. Borlaug, and G. Michael Felker
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clinical outcomes ,heart failure with preserved ejection fraction ,high‐sensitivity troponin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background We sought to study the prevalence of high‐sensitivity troponin and its association with cardiac structure and outcomes in ambulatory and hospitalized patients with heart failure with a preserved ejection fraction (HFpEF). Methods and Results A post hoc analysis utilized data from HFpEF patients: DOSE (Diuretic Optimization Strategies Evaluation) and CARRESS‐HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) enrolled patients hospitalized with acute HFpEF, and RELAX (Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) enrolled ambulatory patients with HFpEF. High‐sensitivity troponin I (hs‐TnI) was measured in hospitalized patients at baseline, at 72 to 96 hours, on day 7, and on day 60. In ambulatory patients hs‐TnI was measured at baseline and at week 24. In the ambulatory cohort, correlations between hs‐TnI and cardiac structure and function were assessed. The association between hs‐TnI and a 60‐day composite of emergency room visits, readmissions, and death was assessed for hospitalized patients using multivariable Cox proportional hazard models. The study population included 139 hospitalized and 212 ambulatory patients with HFpEF and hs‐TnI measured at baseline. The median (25th, 75th percentiles) baseline troponin was 17.6 (11.1, 41.0) ng/L in hospitalized patients and 9.5 (5.3, 19.7) ng/L in ambulatory patients (P99% percentile upper reference limit was 86% in hospitalized patients and 53% among ambulatory patients, with stable elevation in ambulatory patients during follow‐up. HFpEF patients with a hs‐TnI above the median were older with worse left ventricular hypertrophy and diastolic dysfunction. Continuously valued hs‐TnI (per doubling) was associated with increased risk of composite end point (adjusted hazard ratio 1.20, 95% confidence interval 1.00‐1.43; P=0.042). Conclusions Hs‐TnI is commonly elevated among both hospitalized and ambulatory patients with HFpEF. Increased hs‐TnI levels are associated with worse cardiac structure and increased risk of adverse events.
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- 2018
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12. Reduction in Subtypes and Sizes of Myocardial Infarction With Ticagrelor in PEGASUS–TIMI 54
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Marc P. Bonaca, Stephen D. Wiviott, David A. Morrow, P. Gabriel Steg, Christian Hamm, Deepak L. Bhatt, Robert F. Storey, Marc Cohen, Julia Kuder, KyungAh Im, Giulia Magnani, Andrzej Budaj, José C. Nicolau, Alexander Parkhomenko, José López‐Sendón, Mikael Dellborg, Rafael Diaz, Frans Van de Werf, Ramón Corbalán, Assen Goudev, Eva C. Jensen, Per Johanson, Eugene Braunwald, and Marc S. Sabatine
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antiplatelet therapy ,myocardial infarction ,ST‐segment elevation myocardial infarction ,ticagrelor ,troponin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow‐up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for
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- 2018
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13. Cystatin C for Risk Stratification in Patients After an Acute Coronary Syndrome
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Simon Correa, David A. Morrow, Eugene Braunwald, Richard Y. Davies, Erica L. Goodrich, Sabina A. Murphy, Christopher P. Cannon, and Michelle L. O'Donoghue
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acute coronary syndrome ,biomarker ,cystatin C ,prognosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Cystatin C (Cys‐C) is a marker of renal function that has shown prognostic value for cardiovascular risk stratification across different patient populations. The incremental value of Cys‐C beyond established cardiac and renal biomarkers remains incompletely explored. Methods and Results SOLID‐TIMI 52 (Stabilization of Plaques Using Darapladib‐Thrombolysis in Myocardial Infarction 52; www.clinicaltrials.gov, NCT01000727) randomized patients ≤30 days post–acute coronary syndrome were treated with darapladib or placebo. The association between Cys‐C and long‐term risk (median follow‐up 2.5 years) was assessed in 4965 individuals with adjustments made for clinical variables and other risk markers (eg, estimated glomerular filtration rate, high‐sensitivity troponin I, brain‐type natriuretic peptide, and fibroblast growth factor‐23). The prespecified outcome of interest was cardiovascular death (CVD) or heart failure hospitalization. Cys‐C was strongly correlated with creatinine (r=0.60) and estimated glomerular filtration rate (r=−0.68), moderately correlated with fibroblast growth factor‐23 (r=0.39), and weakly correlated with brain‐type natriuretic peptide (r=0.28) and high‐sensitivity troponin I (r=0.06) (all P
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- 2018
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14. Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial
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Christina L. Fanola, Christian T. Ruff, Sabina A. Murphy, James Jin, Anil Duggal, Noe A. Babilonia, Piyamitr Sritara, Michele F. Mercuri, Pieter W. Kamphuisen, Elliott M. Antman, Eugene Braunwald, and Robert P. Giugliano
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anticoagulants ,atrial fibrillation ,cancer ,edoxaban ,malignancy ,warfarin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230–771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78–3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07–2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83–1.42). Relative outcomes with higher‐dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism (HR, 0.60 [95% CI, 0.31–1.15] for malignancy versus HR, 0.89 [95% CI, 0.76–1.05] for no malignancy; interaction P=0.25) and major bleeding (HR, 0.98 [95% CI, 0.69–1.40] for malignancy versus HR, 0.79 [95% CI, 0.69–1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher‐dose edoxaban versus warfarin in patients with malignancy (HR, 0.54; 95% CI, 0.31–0.93) compared with no malignancy (HR, 1.02; 95% CI, 0.88–1.18; interaction P=0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.
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- 2018
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15. Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)
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Eri Toda Kato, Christopher P. Cannon, Michael A. Blazing, Erin Bohula, Sema Guneri, Jennifer A. White, Sabina A. Murphy, Jeong‐Gun Park, Eugene Braunwald, and Robert P. Giugliano
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cholesterol ,chronic ischemic heart disease ,coronary artery disease ,ezetimibe ,lipids and lipoprotein metabolism ,secondary prevention ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundIMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex. Methods and ResultsIn IMPROVE‐IT, patients with acute coronary syndrome and low‐density lipoprotein cholesterol of 50 to 125 mg/dL were randomized to placebo/simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg. They were followed up for a median of 6 years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization ≥30 days, and stroke. Among 18 144 patients in IMPROVE‐IT, 4416 (24%) were women. At 12 months, the addition of ezetimibe to simvastatin significantly reduced low‐density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7 mg/dL in men and 16.4 mg/dL in women). Women receiving ezetimibe/simvastatin had a 12% risk reduction over those receiving placebo/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79–0.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90–1.01; P=0.26 for interaction). When the total number of primary events was considered, women had an 18% reduction with the addition of ezetimibe (relative risk, 95% confidence interval, 0.81; 0.71–0.94) and men had a 6% reduction (relative risk, 0.94; 95% confidence interval, 0.87–1.02; P=0.08 for interaction). The addition of ezetimibe did not increase the rates of safety events in either women or men. ConclusionsIMPROVE‐IT demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid‐lowering therapy to optimize cardiovascular outcomes. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.
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- 2017
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16. Interleukin‐6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52) Trial
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Christina L. Fanola, David A. Morrow, Christopher P. Cannon, Petr Jarolim, Mary Ann Lukas, Christoph Bode, Judith S. Hochman, Erica L. Goodrich, Eugene Braunwald, and Michelle L. O'Donoghue
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acute coronary syndrome ,atherosclerosis ,biomarker ,inflammation ,vascular biology ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundInterleukin‐6 (IL‐6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL‐6 post‐ACS. Methods and ResultsIL‐6 concentration was assessed at baseline in 4939 subjects in SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL‐6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence interval [CI] 1.01‐1.19) and a 22% higher risk of cardiovascular death or heart failure (adj HR 1.22, 95% CI 1.11‐1.34). Patients in the highest IL‐6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95% CI 1.22‐2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6‐3.29). After further adjustment for biomarkers (high‐sensitivity C‐reactive protein, lipoprotein‐associated phospholipase A2 activity, high‐sensitivity troponin I, and B‐type natriuretic peptide), IL‐6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95% CI 1.09‐1.88) and cardiovascular death or heart failure (adj HR 1.79, 95% CI 1.22‐2.63). ConclusionsIn patients after ACS, IL‐6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL‐6 as a potential therapeutic target in patients with unstable ischemic heart disease.
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- 2017
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17. Competing Risks of Cardiovascular Versus Noncardiovascular Death During Long‐Term Follow‐Up After Acute Coronary Syndromes
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Alexander C. Fanaroff, Matthew T. Roe, Robert M. Clare, Yuliya Lokhnygina, Ann Marie Navar, Robert P. Giugliano, Stephen D. Wiviott, Andrew M. Tershakovec, Eugene Braunwald, and Michael A. Blazing
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acute coronary syndrome ,clinical trial ,death ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundUnderstanding the relative risk of cardiovascular versus noncardiovascular death is important for designing clinical trials. These risks may differ depending on patient age, sex, and type of acute coronary syndrome (ACS). Methods and ResultsIMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized controlled trial of simvastatin plus either ezetimibe or placebo following stabilized ACS. Cause of death was adjudicated by an independent committee. We compared the cumulative incidence of cardiovascular and noncardiovascular death for patients with unstable angina/non‐ST‐segment elevation myocardial infarction (UA/NSTEMI) and ST‐segment elevation myocardial infarction (STEMI), in those
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- 2017
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18. Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial
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Alon Eisen, Christian T. Ruff, Eugene Braunwald, Rose A. Hamershock, Basil S. Lewis, Christian Hassager, Tze‐Fan Chao, Jean Yves Le Heuzey, Michele Mercuri, Howard Rutman, Elliott M. Antman, and Robert P. Giugliano
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atrial fibrillation ,digoxin ,heart failure ,mortality ,sudden cardiac death ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). Methods and ResultsIn the ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation‐Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow‐up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10–2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36–2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all‐cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (P
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- 2017
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19. Soluble ST2 in Heart Failure With Preserved Ejection Fraction
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Omar F. AbouEzzeddine, Paul M. McKie, Shannon M. Dunlay, Susanna R. Stevens, G. Michael Felker, Barry A. Borlaug, Horng H. Chen, Russell P. Tracy, Eugene Braunwald, and Margaret M. Redfield
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biomarker ,diastolic heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundSoluble ST2 is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity‐driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF. Methods and ResultsAt enrollment, patients (n=174) from the Phosphodiesterase‐5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HFpEF had sST2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST2 levels. Median sST2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9–49.2 ng/mL; reference range 4–31 ng/mL) and 30.8 ng/mL (range 25.3–39.3 ng/mL; reference range 2–21 ng/mL), respectively. Among HFpEF patients, higher sST2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis (P
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- 2017
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20. Predictors of Nonuse of a High‐Potency Statin After an Acute Coronary Syndrome: Insights From the Stabilization of Plaques Using Darapladib‐Thrombolysis in Myocardial Infarction 52 (SOLID‐TIMI 52) Trial
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Alon Eisen, Christopher P. Cannon, Eugene Braunwald, Dylan L. Steen, Jing Zhou, Erica L. Goodrich, KyungAh Im, Anthony J. Dalby, Jindrich Spinar, Shruti Daga, Mary Ann Lukas, and Michelle L. O'Donoghue
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acute coronary syndrome ,guideline ,secondary prevention ,statin therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundHigh‐potency statins reduce cardiovascular events after acute coronary syndromes but remain underused in clinical practice. We examined predictors of nonuse of high‐potency statins after acute coronary syndromes. Methods and ResultsThe Stabilization of pLaques usIng Darapladib‐Thrombolysis in Myocardial Infarction (SOLID‐TIMI 52) trial enrolled patients after an acute coronary syndrome in 36 countries between 2009 and 2011. Statin use was strongly encouraged throughout the trial, and statin potency was at the discretion of the treating physician. A high‐potency statin was defined as ≥40 mg atorvastatin, ≥20 mg rosuvastatin, or 80 mg simvastatin daily. Predictors of nonuse of high‐potency statins were examined using logistic regression. Of the patients included (n=12 446), 11 850 (95.2%) were treated with a statin at baseline after acute coronary syndrome (median 14 days), but only 5212 (41.9%) were on a high‐potency statin. Selected patient factors associated with nonuse of high‐potency statins included age ≥75 years (odds ratio 1.39, 95% CI 1.24–1.56), female sex (odds ratio 1.11, 95% CI 1.02–1.22), renal dysfunction (odds ratio 1.17, 95% CI 1.03–1.32), and heart failure during hospital admission (odds ratio 1.43, 95% CI 1.27–1.62). At 3 months after baseline, only 49% of patients had low‐density lipoprotein cholesterol
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- 2017
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21. Sudden Cardiac Death in Patients With Atrial Fibrillation: Insights From the ENGAGE AF‐TIMI 48 Trial
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Alon Eisen, Christian T. Ruff, Eugene Braunwald, Francesco Nordio, Ramón Corbalán, Anthony Dalby, Maria Dorobantu, Michele Mercuri, Hans Lanz, Howard Rutman, Stephen D. Wiviott, Elliott M. Antman, and Robert P. Giugliano
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atrial fibrillation ,sudden cardiac death ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundRecent findings suggest that atrial fibrillation is associated with sudden cardiac death (SCD). We examined the incidence, characteristics, and factors associated with SCD in patients with atrial fibrillation. Methods and ResultsSCD was defined as witnessed death ≤60 minutes from the onset of new symptoms or unwitnessed death 1 to 24 hours after being observed alive, without another known cause of death. Predictors of SCD were examined using multivariate competing risks models. Over 2.8 years (median), 2349 patients died (40.5 per 1000 patient‐years), of which 1668 (71%) were cardiovascular deaths. SCD was the most common cause of cardiovascular death (n=749; median age 73 years; 70.6% male). Most SCD events occurred out of hospital (92.8%) and without prior symptoms (66.0%). Predictors of SCD included low ejection fraction, heart failure, and prior myocardial infarction (P
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- 2016
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22. Universal Classification System Type of Incident Myocardial Infarction in Patients With Stable Atherosclerosis: Observations From Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)‐TIMI 50
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Stephen K. Kidd, Marc P. Bonaca, Eugene Braunwald, Gaetano M. De Ferrari, Basil S. Lewis, Piera A. Merlini, Sabina A. Murphy, Benjamin M. Scirica, Harvey D. White, and David A. Morrow
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atherosclerosis ,cardiovascular disease ,myocardial infarction ,platelet inhibitor ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundOur dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated receptor ‐1 antagonist, on new or recurrent MI. Methods and ResultsWe analyzed data from TRA 2°P‐TIMI 50, a multinational, randomized, double‐blind, placebo‐controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73–0.98, P=0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49–1.10, P=0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (≥10× upper reference limit, HR 0.83, CI 0.70–0.98, P=0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, ≥10× upper reference limit, HR 0.81, CI 0.67–0.99, P=0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39–1.11, P=0.12). ConclusionsAmong stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions ≥10× upper reference limit. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.
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- 2016
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23. Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF–TIMI 48 Trial
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Eri Toda Kato, Robert P. Giugliano, Christian T. Ruff, Yukihiro Koretsune, Takeshi Yamashita, Robert Gabor Kiss, Francesco Nordio, Sabina A. Murphy, Tetsuya Kimura, James Jin, Hans Lanz, Michele Mercuri, Eugene Braunwald, and Elliott M. Antman
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antithrombotic ,bleeding ,death ,elderly ,stroke ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundElderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF‐TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age. Methods and ResultsTwenty‐one thousand one‐hundred and five patients enrolled in the ENGAGE AF‐TIMI 48 trial were stratified into 3 prespecified age groups:
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- 2016
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24. Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF‐TIMI48 Trial
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Haiyan Xu, Christian T. Ruff, Robert P. Giugliano, Sabina A. Murphy, Francesco Nordio, Indravadan Patel, Minggao Shi, Michele Mercuri, Elliott M. Antman, and Eugene Braunwald
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anticoagulant ,antiplatelet ,atrial fibrillation ,edoxaban ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundWe studied the concomitant use of single antiplatelet therapy (SAPT) on the efficacy and safety of the anti‐Xa agent edoxaban in patients with atrial fibrillation (AF). Methods and ResultsENGAGE AF‐TIMI 48 was a randomized trial that compared 2 dose regimens of edoxaban with warfarin. We studied both the approved higher‐dose edoxaban regimen (HDER; 60 mg daily reduced by one half in patients with anticipated increased drug exposure), as well as a lower‐dose edoxaban regimen (LDER; 30 mg daily, also reduced by one half in patients with anticipated increased drug regimen). SAPT (aspirin in 92.5%) was administered at the discretion of the treating physician. Cox proportional hazard regressions stratified by SAPT at 3 months with treatment as a covariate were performed. The 4912 patients who received SAPT were more frequently male, with histories of coronary artery disease and diabetes, and had higher CHADS2Vasc and HAS BLED scores than did the 14 997 patients not receiving SAPT. When compared to patients not receiving SAPT, those receiving SAPT had a higher incidence of major bleeding; (adjusted hazard ratio [HRadj]=1.46; 95% CI, 1.27–1.67, P
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- 2016
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25. Hypertrophic cardiomyopathy: The first century 1869–1969
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Eugene Braunwald
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2012
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26. Risks of Heart Failure, Stroke, and Bleeding in Atrial Fibrillation According to Heart Failure Phenotypes
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Riccardo M. Inciardi, Robert P. Giugliano, Jeong-Gun Park, Francesco Nordio, Christian T. Ruff, Cathy Chen, Hans-Joachim Lanz, Elliott M. Antman, Eugene Braunwald, and Scott D. Solomon
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- 2023
27. Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome: A Secondary Analysis From IMPROVE-IT
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Siddharth M. Patel, Arman Qamar, Robert P. Giugliano, Petr Jarolim, Nicholas A. Marston, Jeong-Gun Park, Michael A. Blazing, Christopher P. Cannon, Eugene Braunwald, and David A. Morrow
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Cardiology and Cardiovascular Medicine - Abstract
ImportanceStudies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population.ObjectiveTo evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS).Design, Setting, and ParticipantsThis is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022.Main Outcomes and MeasuresThe outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses.ResultsOf 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change P P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend Conclusions and RelevanceAmong stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT00202878
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- 2023
28. The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial
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Roxana Mehran, Philippe Gabriel Steg, Marc A. Pfeffer, Karola Jering, Brian Claggett, Eldrin F. Lewis, Christopher Granger, Lars Køber, Aldo Maggioni, Douglas L. Mann, John J.V. McMurray, Jean-Lucien Rouleau, Scott D. Solomon, Gregory Ducrocq, Otavio Berwanger, Carmine G. De Pasquale, Ulf Landmesser, Mark Petrie, David Sim Kheng Leng, Peter van der Meer, Martin Lefkowitz, Yinong Zhou, Eugene Braunwald, Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), and Cardiovascular Centre (CVC)
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Heart Failure ,Angiotensins ,Receptors, Angiotensin ,Aminobutyrates ,Biphenyl Compounds ,Tetrazoles ,Stroke Volume ,Angiotensin-Converting Enzyme Inhibitors ,sacubitril and valsartan sodium hydrate drug combination ,neprilysin ,Angiotensin Receptor Antagonists ,Ventricular Dysfunction, Left ,myocardial infarction ,Ramipril ,Physiology (medical) ,Humans ,Valsartan ,Prospective Studies ,Cardiology and Cardiovascular Medicine - Abstract
Background: In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI. Methods: We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. Results: Patients were randomly assigned at a median of 4.4 [3.0–5.8] days after index AMI (ST-segment–elevation myocardial infarction 76%, non–ST-segment–elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74–0.99], P =0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different. Conclusions: In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan—compared with ramipril—reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02924727.
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- 2022
29. Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis
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Eri Toda Kato, David A Morrow, Jianping Guo, David D Berg, Michael A Blazing, Erin A Bohula, Marc P Bonaca, Christopher P Cannon, James A de Lemos, Robert P Giugliano, Petr Jarolim, Tibor Kempf, L Kristin Newby, Michelle L O’Donoghue, Marc A Pfeffer, Nader Rifai, Stephen D Wiviott, Kai C Wollert, Eugene Braunwald, and Marc S Sabatine
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Cardiology and Cardiovascular Medicine - Abstract
Aims Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Methods and results An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints ( 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17–1.31 and HR: 1.16, 95% CI: 1.05–1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90–1.06 and HR: 0.87, 95% CI: 0.39–1.92, respectively). Conclusion Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS.
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- 2022
30. Air pollution: challenges and opportunities for cardiology
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Eugene Braunwald
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Cardiology and Cardiovascular Medicine - Published
- 2023
31. Sacubitril/valsartan versus ramipril for patients with acute myocardial infarction: win‐ratio analysis of the PARADISE‐MI trial
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Otavio Berwanger, Marc Pfeffer, Brian Claggett, Karola S. Jering, Aldo P. Maggioni, Philippe Gabriel Steg, Roxana Mehran, Eldrin F. Lewis, Yinong Zhou, Peter van der Meer, Carmine De Pasquale, Béla Merkely, Gerasimos Filippatos, John J.V. McMurray, Christopher B. Granger, Scott D. Solomon, Eugene Braunwald, Cardiovascular Centre (CVC), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
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Heart Failure ,Aminobutyrates ,Biphenyl Compounds ,Myocardial Infarction ,Tetrazoles ,Stroke Volume ,Acute myocardial infarction ,Ventricular Function, Left ,Sacubitril ,valsartan ,Angiotensin Receptor Antagonists ,Drug Combinations ,NEPRILYSIN INHIBITION ,Ramipril ,Win ratio ,Angiotensin receptor-neprilysin inhibition ,Humans ,Neprilysin ,Cardiology and Cardiovascular Medicine ,COMPOSITE END-POINTS ,CLINICAL-TRIALS - Abstract
Background: \ud The win ratio can incorporate different types of outcomes and enhance statistical power, making it a useful method for analyzing composite outcomes in cardiovascular trials. The application of this approach to the PARADISE-MI trial provides an additional perspective into understanding the effects of sacubitril/valsartan in patients with acute myocardial infarction.\ud \ud Methods: \ud We conducted a post-hoc analysis of the PARADISE-MI trial, which randomly assigned patients with acute myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril/valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to guideline-recommended therapy. The principal composite outcome was analyzed in the hierarchical order of death due to cardiovascular causes, first hospitalization for heart failure, and first outpatient episode of symptomatic heart failure. We included events confirmed by the clinical event classification (CEC) committee as well as events identified by investigators that did not meet study definitions. Results were analyzed by the unmatched win ratio method. A win ratio that exceeds 1.00 reflects a better outcome.\ud \ud Results: \ud A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. The hierarchical analysis of the principal composite outcome demonstrated a larger number of wins [1,265,767 (15.7%)] than losses [1,079,502 (13.4%)] in the sacubitril/valsartan group (win ratio of 1.17, 95% confidence interval [CI],1.03 to 1.33; P=0.015). Sensitivity analyses using alternative definitions of the composite outcome showed results similar to those of the principal analysis, except for analysis restricted to events that met CEC definitions (win ratio of 1.11, 95% CI, 0.96 to 1.30; P=0.16).\ud \ud Conclusion: \ud In this post-hoc analysis of the PARADISE-MI trial using the win ratio and including investigator-identified events not having CEC confirmation, sacubitril/valsartan was superior to ramipril among high-risk survivors of acute myocardial infarction.
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- 2022
32. Tolerability of Sacubitril/Valsartan in Patients With Advanced Heart Failure
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Justin M. Vader, Michael M. Givertz, Randall C. Starling, Steven E. McNulty, Kevin J. Anstrom, Patrice Desvigne-Nickens, Adrian F. Hernandez, Eugene Braunwald, and Douglas L. Mann
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Cardiology and Cardiovascular Medicine - Published
- 2022
33. Neutrophil-lymphocyte ratio and clinical outcomes in 19,697 patients with atrial fibrillation: Analyses from ENGAGE AF- TIMI 48 trial
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Antonio Fagundes Jr., Christian T. Ruff, David A. Morrow, Sabina A. Murphy, Michael G. Palazzolo, Cathy Chen, Petr Jarolim, Elliott M. Antman, Eugene Braunwald, and Robert P. Giugliano
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Cardiology and Cardiovascular Medicine - Published
- 2023
34. Prognostic Importance of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Following High-Risk Myocardial Infarction in the PARADISE-MI Trial
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Karola S. Jering, Brian L. Claggett, Marc A. Pfeffer, Christopher B. Granger, Lars Køber, Eldrin F. Lewis, Aldo P. Maggioni, Douglas L. Mann, John J.V. McMurray, Margaret F. Prescott, Jean L. Rouleau, Scott D. Solomon, Phillippe Gabriel Steg, Dirk von Lewinski, and Eugene Braunwald
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Cardiology and Cardiovascular Medicine - Abstract
Background: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a potent predictor of death and heart failure (HF) across multiple populations. We evaluated the prognostic importance of NT-proBNP in patients with acute myocardial infarction (MI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 risk-augmenting factors enrolled in the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction). Methods: Patients were randomized to sacubitril/valsartan 200 mg or ramipril 5 mg twice daily within 0.5 to 7 days of a MI. Patients with prior HF were excluded. NT-proBNP and hs-cTnT (high-sensitivity troponin T) were collected at randomization in a prespecified substudy of 1129 patients. The primary end point of PARADISE-MI was a composite of cardiovascular death or incident HF (hospitalization or outpatient symptomatic HF), analyzed as time-to-first event; additional end points included all-cause death and the composite of fatal or nonfatal MI or stroke. Results: Median NT-proBNP was 1757 ng/L (25th–75th percentiles, 896–3462 ng/L) at randomization (4.0±1.8 days after the index MI). Patients in the highest quartile of NT-proBNP were older, more commonly women and had more hypertension, atrial fibrillation, renal dysfunction, and pulmonary congestion on presentation (all P P interaction=0.46). Conclusions: Within the first week of a high-risk MI NT-proBNP is associated with incident HF, death and atherosclerotic events. This prognostic information is independent of hs-cTnT. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02924727.
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- 2023
35. Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure
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Robert J. Mentz, Jonathan H. Ward, Adrian F. Hernandez, Serge Lepage, David A. Morrow, Samiha Sarwat, Kavita Sharma, Randall C. Starling, Eric J. Velazquez, Kristin M. Williamson, Akshay S. Desai, Shelley Zieroth, Scott D. Solomon, and Eugene Braunwald
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Cardiology and Cardiovascular Medicine - Published
- 2023
36. Geographic differences in patients with acute myocardial infarction in the <scp>PARADISE‐MI</scp> trial
- Author
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Jawad H. Butt, Brian L. Claggett, Zi M. Miao, Karola S. Jering, David Sim, Peter van der Meer, Mpiko Ntsekhe, Offer Amir, Myeong‐Chan Cho, Jorge Carrillo‐Calvillo, Julio E. Núñez, Alberto Cadena, Prafulla Kerkar, Aldo P. Maggioni, Philippe G. Steg, Christopher B. Granger, Douglas L. Mann, Béla Merkely, Eldrin F. Lewis, Scott D. Solomon, Yinong Zhou, Lars Køber, Eugene Braunwald, John J.V. McMurray, and Marc A. Pfeffer
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2023
37. Serial assessment of biomarkers and heart failure outcomes in patients with atrial fibrillation
- Author
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Kazuma Oyama, Robert P. Giugliano, Christian T. Ruff, David D. Berg, Petr Jarolim, Minao Tang, Jeong‐Gun Park, Hans J. Lanz, Elliott M. Antman, Eugene Braunwald, and David A. Morrow
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2023
38. Mitochondrial cardiomyopathy: a fertile field for research
- Author
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Eugene Braunwald
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2023
39. Changing the Trajectory of Heart Failure and Kidney Disease
- Author
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Janani Rangaswami, Vivek Bhalla, Glenn M. Chertow, Robert A. Harrington, Alexander Staruschenko, Katherine Tuttle, and Eugene Braunwald
- Subjects
Heart Failure ,Male ,Transplantation ,Diabetes Mellitus, Type 2 ,Nephrology ,Epidemiology ,Perspective ,Humans ,Female ,Kidney Diseases ,Critical Care and Intensive Care Medicine ,Sodium-Glucose Transporter 2 Inhibitors - Published
- 2022
40. Foreword
- Author
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Eugene Braunwald, Peter Libby, Robert O. Bonow, Douglas L. Mann, Gordon F Tomaselli, Deepak L. Bhatt, and Scott D. Solomon
- Published
- 2023
41. Assessment of Atherothrombotic Risk in Patients with Type 2 Diabetes Mellitus
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David Berg, Filipe A. Moura, Minao Tang, Benjamin M. Scirica, Stephen Wiviott, David A. Morrow, Deepak L. Bhatt, Itamar Raz, Erin Ann Bohula, Robert P. Giugliano, Jeong-Gun Park, Mark William Feinberg, Eugene Braunwald, and Marc Steven Sabatine
- Subjects
Other health sciences not elsewhere classified ,Cardiology and Cardiovascular Medicine - Abstract
Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention. The purpose of this study was to develop a risk model for atherothrombosis in patients with T2DM.
- Published
- 2023
- Full Text
- View/download PDF
42. Short interfering RNA: a rapidly developing drug class
- Author
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Eugene Braunwald
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
43. In Memoriam: A Tribute to Attilio Maseri
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Valentin Fuster, Eugene Braunwald, and Filippo Crea
- Subjects
business.industry ,MEDLINE ,Medicine ,Tribute ,Cardiology and Cardiovascular Medicine ,business ,Classics - Published
- 2021
44. Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT
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Marc S. Sabatine, Robert P. Giugliano, Jeong-Gun Park, Christopher P. Cannon, Michael A. Blazing, Andrew M. Tershakovec, Eugene Braunwald, and Kazuma Oyama
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medicine.medical_specialty ,Acute coronary syndrome ,Statin ,business.industry ,medicine.drug_class ,Low density lipoprotein cholesterol ,Guideline ,medicine.disease ,Ezetimibe ,Internal medicine ,medicine ,lipids (amino acids, peptides, and proteins) ,Statin therapy ,Cardiology and Cardiovascular Medicine ,business ,Baseline (configuration management) ,medicine.drug ,Cholesterol management - Abstract
Background The 2018 U.S. cholesterol management guideline recommends additional lipid-lowering therapy with ezetimibe for secondary prevention in very high-risk patients with low-density l...
- Published
- 2021
45. Inhibitors of factor XI: game changers of anti-thrombotic therapy?
- Author
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Eugene Braunwald
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
46. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials
- Author
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Christina Reith, Colin Baigent, Lisa Blackwell, Jonathan Emberson, Enti Spata, Kelly Davies, Heather Halls, Lisa Holland, Kate Wilson, Jane Armitage, Charlie Harper, David Preiss, Alistair Roddick, Anthony Keech, John Simes, Rory Collins, Elizabeth Barnes, Jordan Fulcher, William G Herrington, Adrienne Kirby, Borislava Mihaylova, Rachel O'Connell, Pierre Amarenco, Philip Barter, D John Betteridge (deceased), Michael Blazing, Jackie Bosch, Louise Bowman, Eugene Braunwald, Christopher P Cannon, Michael Clearfield, Stuart Cobbe, Helen M Colhoun, Björn Dahlöf, Barry Davis, James de Lemos, John R Downs, Paul N Durrington, Bengt Fellström, Ian Ford, Maria Grazia Franzosi, John Fuller (deceased), Curt Furberg, Robert Glynn, David Gordon, Antonio Gotto Jr, Richard Grimm, Ajay Gupta, C Morton Hawkins, Graham A Hitman, Hallvard Holdaas (deceased), Alan Jardine, J Wouter Jukema, John JP Kastelein, Sharon Kean, John Kjekshus, Genell Knatterud (deceased), Robert H Knopp (deceased), Wolfgang Koenig, Michael Koren, Vera Krane, Martin Landray, John LaRosa, Roberto Latini, Eva Lonn, Donata Lucci, Jean MacFadyen, Peter Macfarlane, Stephen MacMahon, Aldo Maggioni, Roberto Marchioli, Ian Marschner, Lemuel Moyé, Sabina Murphy, Andrew Neil, Enrico B Nicolis, Chris Packard, Sarah Parish, Terje R Pedersen, Richard Peto, Marc Pfeffer, Neil Poulter, Sara Pressel, Jeffrey Probstfield, Mahboob Rahman, Paul M Ridker, Michele Robertson, Frank Sacks, Naveed Sattar, Roland Schmieder, Patrick W Serruys, Peter Sever, John Shaw (deceased), James Shepherd (deceased), Lara Simpson, Peter Sleight (deceased), Luigi Tavazzi, Gianni Tognoni, Andrew Tonkin, Stella Trompet, Christoph Wanner, Hans Wedel, Stephen Weis, K Michael Welch, Harvey White, John Wikstrand, Lars Wilhelmsen, Stephen Wiviott, Robin Young, Salim Yusuf, Faiez Zannad, Hiroyuki Arashi, Robert Byington, Robert Clarke, Marcus Flather, Uri Goldbourt, Shinya Goto, Jemma Hopewell, Kees Hovingh, Patricia Kearney, George Kitas, Connie Newman, Marc S Sabatine, Greg Schwartz, Liam Smeeth, Jonathan Tobert, John Varigos, Junichi Yamaguchi, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, and Collaboration, Cholesterol Treatment Trialists'
- Subjects
Male ,Muscles ,Australia ,Humans ,Female ,General Medicine ,Myalgia ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Middle Aged ,Atherosclerosis ,Randomized Controlled Trials as Topic - Abstract
Background: Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy. Methods: Randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. We analysed individual participant data from 19 double-blind trials of statin versus placebo (n=123 940) and four double-blind trials of a more intensive versus a less intensive statin regimen (n=30 724). Standard inverse-variance-weighted meta-analyses of the effects on muscle outcomes were conducted according to a prespecified protocol. Findings: Among 19 placebo-controlled trials (mean age 63 years [SD 8], with 34 533 [27·9%] women, 59 610 [48·1%] participants with previous vascular disease, and 22 925 [18·5%] participants with diabetes), during a weighted average median follow-up of 4·3 years, 16 835 (27·1%) allocated statin versus 16 446 (26·6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1·03; 95% CI 1·01–1·06). During year 1, statin therapy produced a 7% relative increase in muscle pain or weakness (1·07; 1·04–1·10), corresponding to an absolute excess rate of 11 (6–16) events per 1000 person-years, which indicates that only one in 15 ([1·07–1·00]/1·07) of these muscle-related reports by participants allocated to statin therapy were actually due to the statin. After year 1, there was no significant excess in first reports of muscle pain or weakness (0·99; 0·96–1·02). For all years combined, more intensive statin regimens (ie, 40–80 mg atorvastatin or 20–40 mg rosuvastatin once per day) yielded a higher RR than less intensive or moderate-intensity regimens (1·08 [1·04–1·13] vs 1·03 [1·00–1·05]) compared with placebo, and a small excess was present (1·05 [0·99–1·12]) for more intensive regimens after year 1. There was no clear evidence that the RR differed for different statins, or in different clinical circumstances. Statin therapy yielded a small, clinically insignificant increase in median creatine kinase values of approximately 0·02 times the upper limit of normal. Interpretation: Statin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower than the known cardiovascular benefits. There is a need to review the clinical management of muscle symptoms in patients taking a statin. Funding: British Heart Foundation, Medical Research Council, Australian National Health and Medical Research Council.
- Published
- 2022
47. A polygenic risk score predicts atrial fibrillation in cardiovascular disease
- Author
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Nicholas A Marston, Amanda C Garfinkel, Frederick K Kamanu, Giorgio M Melloni, Carolina Roselli, Petr Jarolim, David D Berg, Deepak L Bhatt, Marc P Bonaca, Christopher P Cannon, Robert P Giugliano, Michelle L O’Donoghue, Itamar Raz, Benjamin M Scirica, Eugene Braunwald, David A Morrow, Patrick T Ellinor, Steven A Lubitz, Marc S Sabatine, and Christian T Ruff
- Subjects
Clinical Research ,Cardiology and Cardiovascular Medicine - Abstract
Aims Interest in targeted screening programmes for atrial fibrillation (AF) has increased, yet the role of genetics in identifying patients at highest risk of developing AF is unclear. Methods and results A total of 36,662 subjects without prior AF were analyzed from four TIMI trials. Subjects were divided into quintiles using a validated polygenic risk score (PRS) for AF. Clinical risk for AF was calculated using the CHARGE-AF model. Kaplan–Meier event rates, adjusted hazard ratios (HRs), C-indices, and net reclassification improvement were used to determine if the addition of the PRS improved prediction compared with clinical risk and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Over 2.3 years, 1018 new AF cases developed. AF PRS predicted a significant risk gradient for AF with a 40% increased risk per 1-SD increase in PRS [HR: 1.40 (1.32–1.49); P < 0.001]. Those with high AF PRS (top 20%) were more than two-fold more likely to develop AF [HR 2.45 (1.99–3.03), P < 0.001] compared with low PRS (bottom 20%). Furthermore, PRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, ranging from a 3-year incidence of 1.3% in patients with low clinical and genetic risk to 8.7% in patients with high clinical and genetic risk. The subgroup of patients with high clinical risk, high PRS, and elevated NT-proBNP had an AF risk of 16.7% over 3 years. The C-index with the CHARGE-AF clinical risk score alone was 0.65, which improved to 0.67 (P < 0.001) with the addition of NT-proBNP, and increased further to 0.70 (P < 0.001) with the addition of the PRS. Conclusion In patients with cardiovascular conditions, AF PRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score and NT-proBNP.
- Published
- 2022
48. Glucose-Insulin-Potassium Therapy for Acute Myocardial Infarction: 50 Years On and Time for a Relook
- Author
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James E. Udelson, Harry P. Selker, and Eugene Braunwald
- Subjects
Glucose ,Physiology (medical) ,Myocardial Infarction ,Potassium ,Humans ,Insulin ,Cardiology and Cardiovascular Medicine - Published
- 2022
49. Cardiac Xenotransplantation: Another Historic First?
- Author
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Eugene, Braunwald
- Published
- 2022
50. Atrial amyloidosis: mechanisms and clinical manifestations
- Author
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Giuseppe Vergaro, Alberto Aimo, Claudio Rapezzi, Vincenzo Castiglione, Iacopo Fabiani, Angela Pucci, Gabriele Buda, Claudio Passino, Josep Lupón, Antoni Bayes‐Genis, Michele Emdin, and Eugene Braunwald
- Subjects
Heart Failure ,Amyloidosis ,Atrial disease ,Atrial fibrillation ,Heart ,Natriuretic peptides ,Atrial Fibrillation ,Humans ,Cardiology and Cardiovascular Medicine - Abstract
Cardiac amyloidosis (CA) is now recognized as an important cause of heart failure. Increased wall thickness and diastolic dysfunction of the left ventricle are the most easily detectable manifestations of CA, but amyloid accumulates in all cardiac structures. Involvement of the left and right atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, the effects of amyloid infiltration into the atrial wall, and the cardiotoxic damage of atrial cardiomyocytes by amyloid precursors. Atrial amyloidosis is an early manifestation of CA, and is associated with an increased risk of atrial fibrillation and thromboembolic events. Furthermore, atrial amyloidosis can be found even in the absence of systemic disease and ventricular involvement. This condition is named isolated atrial amyloidosis and is due to a local overproduction of atrial natriuretic peptide. In this review we summarize the evidence on the mechanisms and clinical relevance of atrial amyloidosis.
- Published
- 2022
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