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Eugene Braunwald

Bio: Eugene Braunwald is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Myocardial infarction & TIMI. The author has an hindex of 230, co-authored 1711 publications receiving 264576 citations. Previous affiliations of Eugene Braunwald include Boston University & University of California, San Francisco.


Papers
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Journal ArticleDOI
TL;DR: In this article, the authors used prospectively defined criteria to assess the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period.
Abstract: Background—The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. Methods and Results—To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, prav...

412 citations

Journal ArticleDOI
TL;DR: This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of a private-sector, expert panel.
Abstract: This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel Principal conclusions include the following (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling

412 citations

Journal Article
TL;DR: Investigations have clearly indicated that stimulation of the vagosympathetic trunk produces a negative inotropic effect in the canine ventricle, and cholinergic and adrenergic influences interact synergistically and antagonistically in their actions upon the heart.
Abstract: In the last decade, evidence has been obtained which indicates that the terminal innervation of the ventricles as well as the atria includes parasympathetic nerve fibers The demonstration of ganglia within the ventricular myocardium suggested the presence of parasympathetic nerve fibers and the vagal nature of these ganglia was supported by their persistence after total surgical cardiac denervation and cardiac transplantation Although it is now clear that parasympathetic fibers are present throughout the ventricles, their density is considerably sparser in these chambers than in the atria Furthermore, the vagal trunkas receive abundant adrenergic fibers from the stellate ganglia via the ansa subclavia and actually are mixed parasympathetic-adrenergic trunks The adrenergic and parasympathetic components of the trunks are unevenly distributed to the ventricles; it appears that greater numbers of adrenergic fibera terminate in the right ventricle and greater numbers of cholinergic fibers in the left ventricle Cholinergic interventions produce their action upon the heart by a variety of mechanisms The inhibitory actions appear to be closely related to their ability to decrease the duration of the action potential and subsequent cellular influx of ionic calcium In addition ACH and choline esters decrease adenylate cyclase activity and cyclic adenosine 3' ,5'-monophosphate accumulation of broken cell preparationa from mammalian atria and ventricles On the other hand, under special conditions, ie , after atropine administration, cholinergic interventions may cause stimulatory effects through interactions with adrenergic and nonadrenergic mechanisms There is now abundant evidence to indicate that ACH releases norepinephrine from depota in the heart; these depots are located predominantly in postganglionic adrenergic nerve fibers In addition, particularly in the presence of conditions tending to lower intracellular ionic calcium, large doses of ACH produce positive inotropic effects on ventricular myocardium, in spite of prior depletion of cardiac catecholamine stores Cholinergic and adrenergic influences interact synergistically and antagonistically in their actions upon the heart It appears that under conditions involving a high level of sympathetic tone, the vagal center in the medulla is inhibited by higher centers in the hypothalamus In addition, cholinergic and adrenergic mechanisms interact at the receptor level, the inhibitory actions of ACH on automaticity and contractility on atrial tissue predominating over the excitatory actions of catecholamines Although an inhibitory effect of the vagi upon ventricular contractility has been questioned for many years, recent investigations have clearly indicated that stimulation of the vagosympathetic trunk produces a negative inotropic effect in the canine ventricle In addition, there is now convincing evidence that stimulation of parasympathetic nerve fibers produces distinct vasodilatation in the coronary vascular bed, independent of its indirect effects on the determinants of myocardial oxygen requirements and myocardial extravascular compression Parasympathetic nerve fibers serve as a component of the efferent limb of the baroreceptor, chemoreceptor, and of other cardiovascular and respiratory reflexes involved in the regulation of cardiac automaticity and contractility Recent studies using a sensitive technique to evaluate the responsiveness of the baroreceptor reflex indicate that reflexly induced parasympathetic stimulation of the heart is attenuated by general anesthesia, during exercise, in hypertensive patients, and in normotensive, elderly patients Observations in man and in experimental animals indicate that parasympathetic tone and parasympathetically medisted reflexes are profoundly depressed in heart failure and in various forms of heart disease

411 citations

Journal ArticleDOI
02 Aug 2016-JAMA
TL;DR: The use of liraglutide did not lead to greater posthospitalization clinical stability among patients recently hospitalized with heart failure and reduced LVEF, and these findings do not support the use ofLiragLutide in this clinical situation.
Abstract: Importance Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. Objective To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. Design, Setting, and Participants Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. Interventions The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. Main Outcomes and Measures The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. Results Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52-68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%-33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054-4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs 16 [11%] in the placebo group; hazard ratio, 1.10 [95% CI, 0.57-2.14]; P = .78) or rehospitalizations for heart failure (63 [41%] vs 50 [34%], respectively; hazard ratio, 1.30 [95% CI, 0.89-1.88]; P = .17) or for the exploratory secondary end points. Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences. The number of investigator-reported hyperglycemic events was 16 (10%) in the liraglutide group vs 27 (18%) in the placebo group and hypoglycemic events were infrequent (2 [1%] vs 4 [3%], respectively). Conclusions and Relevance Among patients recently hospitalized with heart failure and reduced LVEF, the use of liraglutide did not lead to greater posthospitalization clinical stability. These findings do not support the use of liraglutide in this clinical situation. Trial Registration clinicaltrials.gov Identifier:NCT01800968

411 citations

Journal ArticleDOI
TL;DR: There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.
Abstract: In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/- 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.

403 citations


Cited by
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Journal ArticleDOI
21 May 2003-JAMA
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

24,988 citations

Book
23 Sep 2019
TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

21,235 citations

Journal ArticleDOI
TL;DR: Atherosclerosis is an inflammatory disease as discussed by the authors, and it is a major cause of death in the United States, Europe, and much of Asia, despite changes in lifestyle and use of new pharmacologic approaches to lower plasma cholesterol concentrations.
Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

19,881 citations

Journal ArticleDOI
TL;DR: Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups.
Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

17,213 citations

Journal ArticleDOI
TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

14,975 citations