Showing papers by "Eugene Braunwald published in 2010"
TL;DR: Individuals with the ABCB1 3435C→T genotype have reduced platelet inhibition and are at increased risk of recurrent ischaemic events during clopidogrel treatment, and in patients with acute coronary syndromes who have undergone percutaneous intervention, this polymorphism is significantly associated with the risk of cardiovascular death, myocardial infarction, or stroke.
564 citations
TL;DR: In this paper, a phase 3 comparison of the novel oral factor Xa inhibitor edoxaban to warfarin for the prevention of thromboembolism in patients with atrial fibrillation was conducted.
441 citations
TL;DR: Among acute coronary syndrome patients with planned percutaneous coronary intervention, treatment with prasugrel versus clopidogrel for up to 15 months is an economically attractive treatment strategy.
Abstract: Background— In patients with acute coronary syndromes and planned percutaneous coronary intervention, the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) demonstrated that treatment with prasugrel versus clopidogrel was associated with reduced rates of cardiovascular death, MI, or stroke and an increased risk of major bleeding. We evaluated the cost-effectiveness of prasugrel versus clopidogrel from the perspective of the US healthcare system by using data from TRITON-TIMI 38. Methods and Results— Detailed resource use data were prospectively collected for all patients recruited from 8 countries (United States, Australia, Canada, Germany, Italy, Spain, United Kingdom, and France; n=3373 prasugrel, n=3332 clopidogrel). Hospitalization costs were estimated on the basis of diagnosis-related group and in-hospital complications. Cardiovascular medication costs were estimated by using net wholesale pri...
149 citations
TL;DR: Low-level increases in cTnI using a sensitive assay identify patients at higher risk of death or MI, and the incremental value of newer, more sensitive assays in identifying high-risk patients with ACS is supported.
133 citations
TL;DR: Nonsustained VT is common after admission for non–ST-elevation acute coronary syndrome, and even short episodes of VT lasting 4 to 7 beats are independently associated with the risk of SCD over the subsequent year.
Abstract: Background—Most studies examining the relationship between ventricular tachycardia (VT) after acute coronary syndrome and sudden cardiac death (SCD) were performed before widespread use of reperfusion, revascularization, or contemporary medical therapy and were limited to ST-elevation myocardial infarction. The incidence and prognostic implications of VT in patients with non–ST-elevation acute coronary syndrome receiving contemporary care have not been examined. Methods and Results—The Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) trial randomized 6560 patients hospitalized with a non–ST-elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG recording was performed for the first 7 days after randomization and evaluated in a blinded core laboratory. SCD (n=121) was assessed over a median follow-up of 1 year. A total of 6345 patients (97%) had con...
113 citations
96 citations
Cleveland Clinic1, Harvard University2, Ohio State University3, Mayo Clinic4, University of Maryland, Baltimore5, University of Cincinnati6, University of California, Davis7, University of California, Los Angeles8, University of Pennsylvania9, Emory University10, Northwestern University11, Wayne State University12, University of California, San Diego13, University of California, San Francisco14, Veterans Health Administration15, Duke University16, National Institutes of Health17, Vanderbilt University18
TL;DR: Recommendations include proposals regarding the design and conduct of emergency department-based clinical trials, suggestions regarding the development of improved methods for early detection and monitoring of AHFS, and potential needs for expanding translational and applied AHFS focused research and biotechnology.
85 citations
TL;DR: It is indicated that smoking cessation is beneficial after high-risk MI and the importance of smoking cessation as a therapeutic target in patients with LV dysfunction after MI is highlighted.
Abstract: Patients with left ventricular (LV) systolic dysfunction after myocardial infarction (MI) are at particularly high risk for recurrent adverse outcomes. The magnitude of the decrease in risk associated with smoking cessation after MI has not been well described in patients with LV dysfunction after MI. We aimed to quantify the risk decrease associated with smoking cessation in subjects with LV dysfunction after MI. The Survival and Ventricular Enlargement (SAVE) trial randomized 2,231 subjects with LV dysfunction 3 to 16 days after MI. Smoking status was assessed at randomization and at regular intervals during a median follow-up of 42 months. Propensity score-adjusted Cox proportional hazard models were used to quantify the decrease in risk of all-cause mortality, death or recurrent MI, and death or heart failure (HF) hospitalization associated with smoking cessation. In baseline smokers who survived to 6 months without interval events, smoking cessation at 6-month follow-up was associated with a significantly lower adjusted risk of all-cause mortality (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.31 to 0.91), death or recurrent MI (HR 0.68, 95% CI 0.47 to 0.99), and death or HF hospitalization (HR 0.65, 95% CI 0.46 to 0.92). In conclusion, in patients with LV dysfunction after MI, smoking cessation is associated with a 40% lower hazard of all-cause mortality and a 30% lower hazard of death or recurrent MI or death or HF hospitalization. These findings indicate that smoking cessation is beneficial after high-risk MI and highlight the importance of smoking cessation as a therapeutic target in patients with LV dysfunction after MI.
84 citations
TL;DR: Ranolazine, when added to concurrent antidiabetes treatment, lowers FPG and A1C in patients with cardiovascular disease and poorly controlled diabetes.
Abstract: OBJECTIVE — We determined the relationships between glycemia at randomization, concurrent antidiabetic therapy, and change in A1C and fasting plasma glucose (FPG) in patients with diabetes receiving standard treatment for diabetes and randomized to ranolazine or placebo within the MERLIN-TIMI-36 (MERLIN) study. Ranolazine is a novel first-in-class drug approved for treating angina pectoris. RESEARCH DESIGN AND METHODS — Randomization and 4-month glycemic and antidiabetes drug usage data from MERLIN were analyzed using Spotfire and SAS version 9.1 software. RESULTS — In patients with diabetes and A1C of 8 –10% at randomization (n 171), there was an absolute A1C reduction in the ranolazine group of 1.2% (95% CI 1.4 to 1.0), and the placebo-adjusted (n 182) decrease in A1C by ranolazine was 0.59% (95% CI 0.99 to0.20,P 0.001). In patients with FPG of 150 – 400 mg/dl at randomization, ranolazine (n 131) compared with placebo (n 147) reduced FPG by 25.7 mg/dl (95% CI43.3 to8.1,P 0.001). When changes in either A1C or FPG were correlated to A1C or FPG at randomization, the slopes were significantly steeper for ranolazine than placebo (A1C, P 0.046; FPG, P 0.001), indicating that lowering of A1C and FPG by ranolazine is related to hyperglycemia at randomization. Ranolazine, compared with placebo, was not associated with serious hypoglycemic events, associated with significant changes in concurrent antidiabetic therapy, or dependent on a history of angina. CONCLUSIONS — Ranolazine, when added to concurrent antidiabetes treatment, lowers FPG and A1C in patients with cardiovascular disease and poorly controlled diabetes. Diabetes Care 33:1163–1168, 2010
73 citations
TL;DR: Among ACS patients presenting with isolated anterior ST-segment depression, over one-quarter had an occluded culprit artery and elevated cardiac biomarkers, and these patients had significantly worse clinical outcomes, and few underwent urgent angiography.
Abstract: Objectives This study sought to determine angiographic and clinical outcomes among patients with acute coronary syndrome (ACS) presenting with isolated anterior ST-segment depression on 12-lead electrocardiogram (ECG). Background In patients with ACS, anterior ST-segment depression on 12-lead ECG may represent plaque rupture with: 1) acute thrombotic occlusion with elevation of cardiac biomarkers (+Tn); 2) a patent artery with +Tn; or 3) a patent artery with –Tn. Methods The TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction 38) enrolled 13,608 ACS patients. Those with isolated anterior (leads V1 to V4) ST-segment depression were analyzed. Angiograms and ECGs were interpreted by local investigators. Results There were 1,198 (8.8%) patients with isolated anterior ST-segment depression. Of those, 314 (26.2%) had an occluded culprit artery (TIMI flow grade 0/1) and +Tn, 641 (53.5%) had a patent culprit artery (TIMI flow grade 2/3) and +Tn, and 243 (20.3%) had TIMI flow grade 2/3 and –Tn. Among patients with an occluded artery, the culprit artery was most often the left circumflex artery (48.4%). The 30-day incidence of the composite of death and MI was significantly higher among patients with an occluded artery (8.6%) than among those with a patent culprit artery and either +Tn (6.3%) or –Tn (2.9%) (3-way p = 0.006). Among patients with an occluded artery, the median time from ECG to percutaneous coronary intervention was 29.4 h (interquartile range 26.1 to 44.1 h). Conclusions Among ACS patients presenting with isolated anterior ST-segment depression, over one-quarter had an occluded culprit artery and elevated cardiac biomarkers. These patients had significantly worse clinical outcomes, and few underwent urgent angiography.
71 citations
TL;DR: The underlying assumptions and the existing evidence supporting a natriuretic-peptide-guided approach to the outpatient management of HF are addressed.
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Testing for natriuretic peptide markers, such as B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP), has emerged as an important tool for the diagnosis and risk stratification of patients with HF. However, questions remain regarding the potential role for natriuretic peptides to guide therapy in patients with HF. In this Review, we address the underlying assumptions and the existing evidence supporting a natriuretic-peptide-guided approach to the outpatient management of HF.
TL;DR: It is indicated that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP, and the interaction of biomarkers of hemodynamic stress and the effects of ranolazines warrants additional investigation.
TL;DR: In a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS, there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan, aliskiren, or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy.
Abstract: Aims Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin–angiotensin–aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo.
Methods and results AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function ≤40% but with an increased level of NP 3–10 days after admission to aliskiren, valsartan, their combination, and placebo. The primary endpoint was the change in NT-proBNP from baseline to Week 8. NT-proBNP declined significantly in each treatment arm, including placebo, by Week 8, though there were no differences in the reduction between treatment strategies (42% in placebo, 44% in aliskiren, 39% in valsartan, and 36% in combination arm). Although several subgroups had higher baseline levels of NP and greater reductions over the study period, there were no differences among treatment groups in any subgroup. There were no differences in clinical outcomes but there were more adverse events, including serious events and adverse events leading to early study drug discontinuation, in patients treated with active therapy.
Conclusion In this study of a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS, there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan, aliskiren, or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy. Moreover, adverse events were reported more frequently in patients assigned to active therapy.
TL;DR: Prior aspirin use was associated with more comorbidities and coronary disease and a higher risk of recurrent MI, but not mortality, and should best be considered a marker of a patient population at high risk for recurrent adverse events after ACS.
TL;DR: Cardiogenic shock, age, and ICH were important independent correlates of 30-day and 1-year mortality in STEMI patients receiving fibrinolytic therapy as well as in-hospital non-ICH major and minor bleeding.
Abstract: Aims To evaluate the association of bleeding with mortality in ST-elevation myocardial infarction (STEMI).
Methods and results We studied 20 323 patients with STEMI receiving fibrinolytic therapy and an antithrombin in ExTRACT-TIMI 25. Relationships between in-hospital bleeding, patient characteristics, treatments, and in-hospital cardiovascular complications with mortality were evaluated using Cox models. Likelihood ratios estimated each variable's model contribution. High 30-day mortality after major bleeding ( n = 309, 37.6% mortality) was driven by the poor prognosis of intracranial haemorrhage (ICH; n = 143, 65.4% mortality, model contribution 7.8%). The adjusted hazard ratios (HRs) for 30-day death for any major bleeding and for ICH were 2.9 [2.4–3.6] and 10.3 [8.2–12.8], respectively. Neither non-ICH major nor minor bleeding was associated with 30-day death after adjustment. Cardiogenic shock (HR 13.5, 61% contribution) and age (HR 1.6/decade, 17% contribution) were most strongly correlated with 30-day death. Among 30-day survivors, age (HR 1.6/decade, contribution 43%) and heart rate (HR 1.2 per 10 b.p.m., contribution 18%) were most strongly associated with mortality between Days 31 and 365.
Conclusion Cardiogenic shock, age, and ICH were important independent correlates of 30-day and 1-year mortality in STEMI patients receiving fibrinolytic therapy. In-hospital non-ICH major and minor bleeding were not independently associated with increased mortality at 30 days or 1 year.
TL;DR: Data is summarized and compared on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation.
Abstract: Arterial and venous thromboembolism account for significant morbidity and mortality worldwide. Warfarin, and other vitamin K antagonists (VKAs), have been the only class of oral anticoagulants currently in clinical use and have been so for over 50 years. Although warfarin is effective in preventing thromboembolism, its use is limited by its narrow therapeutic index that necessitates frequent monitoring and dose adjustments resulting in considerable inconvenience to patients and clinicians. There are now several orally administered anticoagulants in late stages of clinical development that may offer effective, safer, and more convenient anticoagulation. This review summarizes and compares data on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation.
TL;DR: Baseline TnT and 90-minute STRes are independent predictors of 30-day CV death in patients with STEMI and use of these 2 simple, readily available tools can aid clinicians in early risk stratification.
TL;DR: Compared with UFH for 48 h, a strategy using enoxaparin as an adjunct to fibrinolysis resulted in a sustained reduction in death or MI at 1 year with no additional benefit after 30 days.
Abstract: Aims To determine the impact of a strategy using enoxaparin for up to 8 days compared with unfractionated heparin (UFH) for 48 h as an adjunct to fibrinolysis for ST-segment elevation myocardial infarction (STEMI) on 1-year clinical outcomes.
Methods and results Follow-up at 1 year ( n = 20 275) was conducted by telephone in the ExTRACT-TIMI 25 trial to ascertain the endpoints of death, MI, and disabling stroke. The primary endpoint of death or non-fatal MI occurred in 1614 (15.8%) and 1732 (17.0%) of patients allocated to enoxaparin and UFH, respectively [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.86–0.98, P = 0.01]. The enoxaparin strategy significantly reduced non-fatal MI at 1 year (5.7 vs. 6.8%, HR 0.82, 95% CI 0.73–0.92, P < 0.001). The risks of death (10.5 vs. 10.6%, HR 0.98, 95% CI 0.91–1.07) and disabling stroke (1.1 vs. 1.2%, HR 0.97, 95% CI 0.75–1.26) were not reduced. The composite of death, MI, or disabling stroke favoured enoxaparin (HR 0.91, 95% CI 0.85–0.98, P = 0.007).
Conclusion Compared with UFH for 48 h, a strategy using enoxaparin as an adjunct to fibrinolysis resulted in a sustained reduction in death or MI at 1 year with no additional benefit after 30 days. Mortality was not reduced at 1 year with the enoxaparin strategy.
The study was registered at ClinicalTrials.gov, NCT00077792.
TL;DR: The extent of STRes based on routinely obtained ECGs is an independent predictor of death and heart failure when used together with the TIMI risk score and significantly improves the ability to risk stratify patients after fibrinolysis.
TL;DR: James W. Black conducted research and published his first article on the effects of 5-hydroxytryptamine on gastric acid secretions, which stimulated his lifelong research work on intestinal absorption of carbohydrates.
Abstract: James W. Black was born in Lanarkshire, a coal mining district of Scotland, on June 14, 1924 and died in London on March 22, 2010. He was the fourth of five sons of a mining engineer and a housewife. His family could not afford to send him to university, but at the age of 15, on the advice of his high school mathematics teacher, he applied for and won a scholarship to nearby St Andrew’s University, where, under the influence of an older brother, he attended its medical school. His clinical training in medical school was at University College, which subsequently became the University of Dundee. (Black served as Chancellor of his alma mater later, vide infra.)
He decided not to practice medicine because of what he perceived to be “insensitive” treatment of patients that he had observed. Instead, on graduation, he joined the Physiology Department of St Andrews as an Assistant Lecturer and began his research career in Professor R. C. Garry’s laboratory, where he studied the intestinal absorption of carbohydrates. In 1947, Black and his new wife, the former Hilary Vaughan whom he had met at St Andrews, moved to Singapore, where he served for 3 years as a Lecturer in Physiology at the King Edward VII College of Medicine, University of Malaya. That move was necessitated, subsequently described by Black, as: “an inevitable result of marriage, debts accumulated to pay for the completion of my medical studies, and pitiful academic prospects.”1 On returning to Scotland in 1950, he became Senior Lecturer and Head of the Department of Physiology at the new Glasgow Veterinary School, where he built a state-of-the-art physiology teaching laboratory. He conducted research and published his first article on the effects of 5-hydroxytryptamine on gastric acid secretions.2 This early work stimulated his lifelong …
TL;DR: In the January 2010 issue of Nature Reviews Cardiology, errors were published in Figure 4 (page 18) of the Review article by Michelle O'Donoghue and Eugene Braunwald, where the key for the Kaplan-Meier curves was incorrect.
Abstract: Nat. Rev. Cardiol. 7, 13–20 (2010); doi:10.1038/nrcardio.2009.197 In the January 2010 issue of Nature Reviews Cardiology, errors were published in Figure 4 (page 18) of the Review article by Michelle O'Donoghue and Eugene Braunwald. The key for the Kaplan-Meier curves was incorrect. In parts a to d,the red, solid line should represent NT-BNP-guided therapy and the blue, dashed line should represent symptom-guided therapy.
Journal Article•
TL;DR: Heart failure may be associated with preserved (HFpEF) or reduced (HFrEF) ejection fraction or both and acute HF decompensation (AHF) is associated with impaired renal hemodynamics and acti...
Abstract: Introduction: Heart failure (HF) may be associated with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Acute HF decompensation (AHF) is associated with impaired renal hemodynamics and acti...
TL;DR: In this article, the impact of cancer on the risk of cardiovascular events and bleeding was not explicitly accounted for in the analysis of cancer risk in the Saskatchewan Health Database (SHDB).
Abstract: Dr Serebruany raises 3 issues with regard to our analysis1: (1) Failure to account for an increased incidence of cancer; (2) use of the Saskatchewan Health database for prognostic modeling; and (3) differential effects across patient subgroups.
With regard to cancer, Dr Serebruany is correct that we have not explicitly accounted for the impact of cancer in our analysis. There are several reasons behind this approach. First of all, our analysis plan was developed prospectively, long before the trial results were available. For reasons of expediency, our data collection focused on those events that were expected to be impacted by the treatments under consideration (ie, cardiovascular events and bleeding). Consequently, we did not collect specific data on resource utilization associated with cancer and were unable to include this information in our analysis. More importantly, however, it should be noted that the excess risk of cancer that Dr Serebruany alludes to was not actually identified in the Food and …
01 Jan 2010
TL;DR: It is argued that Dr. Braunwald's research has had a major impact on cardiovascular medicine, greater than that of any other contemporary investigator.
Abstract: What can I say, in one paragraph, about Dr. Braunwald’s research contributions? Surely it won’t be enough to point out that he has laid the foundations of classic chapters of cardiovascular physiology, such as myocardial oxygen consumption, cardiac mechanics, and cardiovascular hemodynamics. Or that he has been pivotal in identifying the etiology, pathogenesis, and treatment of hypertrophic cardiomyopathy. Or that he has created and spearheaded the concept of infarct size limitation (inspiring my own scientific career). Or that he has illuminated our understanding of heart failure and revolutionized the management of postinfarction left ventricular remodeling. Or that he has led more than 50 TIMI trials, which have transformed the management of acute coronary syndromes. No, that won’t do, because this list is woefully incomplete. There is so much more. I think the best way to put it is that his research has had a major impact on cardiovascular medicine, greater than that of any other contemporary investigator.