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Showing papers by "Eugene Braunwald published in 2002"


Journal ArticleDOI
TL;DR: These revised guidelines for the management of unstable angina and non–ST-segment elevation myocardial infarction were published in September 2000 and the present article describes these revisions and provides further updates in this rapidly moving field.
Abstract: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the management of unstable angina and non–ST-segment elevation myocardial infarction (UA/NSTEMI) were published in September 2000.1 Since then, a number of clinical trials and observational studies have been published or presented that, when taken together, alter significantly the recommendations made in that document. Therefore, the ACC/AHA Committee on the Management of Patients With Unstable Angina, with the concurrence of the ACC/AHA Task Force on Practice Guidelines, revised these guidelines. These revisions were prepared in December 2001, reviewed and approved, and then published on the ACC World Wide Web site (www.acc.org) and AHA World Wide Web site (www.americanheart.org) on March 15, 2002. The present article describes these revisions and provides further updates in this rapidly moving field. Minor clarifications in the wording of three recommendations that now appear differently from those that were previously published on the ACC and AHA Web sites are noted in footnotes. The ACC/AHA classifications I, II, and III are used to summarize indications as follows: Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective. Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. IIa: Weight of evidence/opinion is in favor of usefulness/efficacy. IIb: Usefulness/efficacy is less well established by evidence/opinion. Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful. The weight of the evidence was ranked highest (A) if the data were derived from multiple randomized clinical trials that involved large numbers of patients and intermediate (B) if the data were derived from a limited number of randomized trials that involved small numbers of …

1,496 citations


Journal ArticleDOI
TL;DR: Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS and a simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events.
Abstract: Background— In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination. Methods and Results— Baseline measurements of TnI, CRP, and BNP were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment fo...

765 citations


Journal ArticleDOI
TL;DR: Right ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI, after adjusting for age, gender, diabetes mellitus, hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment assignment.

415 citations


Journal ArticleDOI
TL;DR: Both improved epicardial flow (TFG 2/3 and low CTFCs) and tissue-level perfusion at 90 minutes after thrombolytic administration are independently associated with improved 2-year survival, suggesting complementary mechanisms of improved long-term survival.
Abstract: Background— Although 90-minute TIMI flow grades (TFGs), corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grades (TMPGs) have been associated with 30-day outcomes, we hypothesized that these indices would be related to long-term outcomes after thrombolytic administration. Methods and Results— As a substudy of the TIMI 10B trial (tissue plasminogen activator versus tenecteplase), 49 centers carried out 2-year follow-up. TIMI grade 2/3 flow (Cox hazard ratio [HR] 0.41, P=0.001), reduced CTFCs (faster flow, P=0.02), and an open microvasculature (TMPG 2/3) (HR 0.51, P=0.038) were all associated with improved 2-year survival. Rescue percutaneous coronary intervention (PCI) of closed arteries (TFG 0/1) at 90 minutes was associated with reduced mortality (P=0.03), and mortality trended lower with adjunctive PCI of open (TFG 2/3) arteries (P=0.11). In a multivariate model correcting for previously identified correlates of mortality (age, sex, pulse, left anterior descending coronary artery infarc...

372 citations


Journal ArticleDOI
25 Dec 2002-JAMA
TL;DR: Despite differences between women and men in baseline characteristics, the benefit of an early invasive strategy incorporating tirofiban and intracoronary stents was similar in women andMen and was enhanced in women presenting with markers of increased risk.
Abstract: ContextWomen who present with acute coronary syndromes (ACSs) have different characteristics than men. Reports have conflicted about whether different outcomes exist for women with use of a routine invasive management strategy. However, these studies were performed prior to the widespread use of platelet glycoprotein IIb/IIIa inhibitors and intracoronary stents.ObjectiveTo determine sex differences in baseline characteristics and outcomes in ACS and whether women benefit from a contemporary early invasive management strategy.Design and SettingProspective analysis of women and men enrolled in the TACTICS-TIMI 18 randomized trial, conducted December 1997 to December 1999 in 169 centers in 9 countries in North America and Europe, with follow-up at 1 and 6 months.ParticipantsA total of 2220 patients (757 women and 1463 men) with ACS.InterventionsAll patients received aspirin, 325 mg/d; intravenous unfractionated heparin; and tirofiban for 48 hours or until revascularization, with tirofiban administered for at least 12 hours after percutaneous coronary revascularization. Patients assigned to the early invasive strategy (n = 1114) underwent coronary angiography 4 to 48 hours after randomization and revascularization when appropriate. Patients assigned to the early conservative strategy (n = 1106) were treated medically and underwent coronary angiography and appropriate revascularization only if they met specified criteria.Main Outcome MeasuresBaseline characteristics and the primary composite end point of death, myocardial infarction, or rehospitalization for ACS at 6 months in women and men assigned to early invasive vs conservative management.ResultsWomen were older and more frequently had hypertension (P<.001 for both). Women less frequently had previous myocardial infarction, coronary artery bypass grafting, and elevations in cardiac markers (P<.001 for all), but there was no difference in distribution of TIMI risk scores (P = .76). Angiography and intervention rates were similar, but women had less severe coronary artery disease, including no critical lesions in 17% of women vs 9% of men (P<.001). Women had a 28% odds reduction in the primary end point with an early invasive strategy (adjusted odds ratio [OR], 0.72; 95% confidence interval [CI], 0.47-1.11), similar to the benefit in men (adjusted OR, 0.64; 95% CI, 0.47-0.88; P = .60 for sex interaction). When adjusted for baseline characteristics, the benefit of invasive therapy in women with elevated troponin T levels was further enhanced (adjusted OR, 0.47; 95% CI, 0.26-0.83).ConclusionsDespite differences between women and men in baseline characteristics, the benefit of an early invasive strategy incorporating tirofiban and intracoronary stents was similar in women and men and was enhanced in women presenting with markers of increased risk.

260 citations



Journal ArticleDOI
TL;DR: In this paper, the authors evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab.
Abstract: Background— ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab. Methods and Results— Patients (n=483) with ST-elevation MI presenting <6 hours from symptom onset were randomized to full-dose TNK and either unfractionated heparin (UFH) (bolus 60 U/kg; infusion 12 U/kg per hour) or enoxaparin (1.0 mg/kg subcutaneously every 12 hours±initial 30 mg intravenous bolus), or half-dose TNK plus abciximab and either UFH (bolus 40 U/kg; infusion 7 U/kg per hour) or enoxaparin (0.3 to 0.75 mg/kg subcutaneously every 12 hours±initial intravenous bolus of 30 mg). With full-dose TNK and UFH, the rate of TIMI 3 flow at 60 minutes was 52% and was 48% to 51% with enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47% to 58% with enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among enoxaparin patients. Through 30 days, death/recurrent MI occurred in the full-dose TNK group in 15.9% of patients with UFH and 4....

249 citations


Journal ArticleDOI
TL;DR: This prospective analysis indicates that during prolonged exposure, 40 mg of pravastatin is well tolerated, with no excess of noncardiovascular serious adverse events, including liver function abnormalities and laboratory and clinical evidence for myositis.
Abstract: Background— Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data. Clinical trials designed to assess efficacy are often insufficiently powered to generate reliable safety data. Methods and Results— The West of Scotland Coronary Prevention Study (WOSCOPS), the Cholesterol and Recurrent Events (CARE), and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies collectively accumulated >112 000 person-years of exposure in double-blind randomized trials comparing placebo and pravastatin (40 mg once daily). During 5 years of exposure, the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups. No differences in noncardiovascular serious adverse events were detected. With >243 000 blood sample analyses, the percentage of patients with any abnormal liver function test after baseline sampling was similar (>3× the upper limit of normal for alanine aminotransferase: 128 [1.4%] versus 131 [1...

243 citations


Journal ArticleDOI
TL;DR: Direct thrombin inhibitors are superior to heparin for the prevention of death or myocardial infarction in patients with acute coronary syndromes, and this information should prompt further clinical development of direct throm bin inhibitors for the management of arterial thrombosis.

228 citations


Journal ArticleDOI
TL;DR: The TIMI Risk Score is a simple clinical tool for risk assessment that may aid in the early identification of patients who should be considered for treatment with potent antiplatelet therapy.
Abstract: Aims We evaluated the TIMI Risk Score for Unstable Angina and Non-ST Elevation Myocardial Infarction for predicting clinical outcomes and the efficacy of tirofiban in non-ST elevation acute coronary syndromes. Methods and Results Developed in TIMI 11B, the risk score is calculated as the sum of seven presenting characteristics (age ≥65 years, ≥3 cardiac risk factors, documented coronary disease, recent severe angina, ST deviation ≥0·5mm, elevated cardiac markers, prior aspirin use). The risk score was validated in the PRISM-PLUS database (n=1915) and tested for interaction with the efficacy of tirofiban+heparin vs heparin alone. The risk score revealed an increasing gradient of risk for death, myocardial infarction or recurrent ischaemia at 14 days ranging from 7·7–30·5% ( P <0·001). Dichotomized at the median, patients with a score ≥4 derived a greater relative risk reduction with tirofiban ( P (Interaction)=0·025). Among patients with normal creatine kinase myocardial bands, the risk score showed a 3·5-fold gradient of risk ( P <0·001) and identified a population that derived significant benefit from tirofiban (RR 0·73, P =0·027). Conclusion The TIMI Risk Score is a simple clinical tool for risk assessment that may aid in the early identification of patients who should be considered for treatment with potent antiplatelet therapy.

213 citations


Journal ArticleDOI
TL;DR: In two large secondary prevention trials of pravastatin, risk reduction was not significant in participants who had low baseline LDL-C concentrations (that is, <125 mg/dL). as discussed by the authors conducted exploratory analyses of participant characteristics, lipid risk factors, and risk reduction in this group.
Abstract: Background— In two large secondary prevention trials of pravastatin, risk reduction was not significant in participants who had low baseline LDL-C concentrations (that is, <125 mg/dL). We conducted exploratory analyses of participant characteristics, lipid risk factors, and risk reduction in this group. Methods and Results— Among 13 173 participants with coronary heart disease (CHD), 2607 had baseline LDL-C <125 mg/dL. Those with LDL-C <125 compared with ≥125 mg/dL were more likely to be diabetic (15% versus 9%), hypertensive (46 versus 41%), and male (89% versus 83%); they had higher triglycerides (169 versus 154 mg/dL), lower HDL-C (36.5 versus 38 mg/dL), and similar body mass index (27 kg/m2); and pravastatin lowered their LDL-C by 36 mg/dL (32%) versus 45 mg/dL (29%). During 5.8-year (mean) follow-up, HDL-C and triglycerides were both significantly stronger predictors of recurrent CHD events in participants with LDL-C <125 than ≥125 mg/dL. In diabetic participants with low LDL-C, pravastatin decreased...

Journal ArticleDOI
TL;DR: It is suggested that Nt-proBNP measurements provide complementary prognostic information to conventional risk indicators, including troponin I, in patients with non-ST-segment elevation acute coronary syndromes.
Abstract: In summary, we have shown that circulating Nt-proANP and Nt-proBNP levels are associated with early death, but not with nonfatal recurrent AMI, in patients with non-ST-segment elevation acute coronary syndromes. This nested case-control study suggests that Nt-proBNP measurements provide complementary prognostic information to conventional risk indicators, including troponin I.

Journal ArticleDOI
TL;DR: Prehospital administration of rPA is a feasible approach to accelerating reperfusion in patients with STEMI and valuable time savings can be achieved in the setting of contemporary transport and door-to-drug times and may translate into an improvement in clinical outcomes.

Journal ArticleDOI
TL;DR: This discussion of the evaluation and management of hypertrophic cardiomyopathy revolves around two illustrative cases of patients initially believed to have congenital or valvular subaortic stenosis and a 42-year-old woman referred for evaluation of progressive exertional dyspnea and fatigue.
Abstract: This discussion of the evaluation and management of hypertrophic cardiomyopathy revolves around two illustrative cases. A 42-year-old woman was referred for evaluation of progressive exertional dyspnea and fatigue over the past 2 years. Both symptoms were greatly intensified during paroxysms of atrial fibrillation, which occur every 3 or 4 months. The patient was asymptomatic until 5 years ago, when she suffered a single syncopal episode precipitated by a bout of coughing in the erect position. She subsequently experienced episodes of presyncope under similar circumstances and at increasing frequency, but she learned to abort frank syncope by immediately lying or sitting down. Examination revealed a grade 3/6 systolic murmur along the left sternal border and at the apex. The diagnosis of obstructive hypertrophic cardiomyopathy (HCM) was established by 2-dimensional and Doppler echocardiography, which showed asymmetric septal hypertrophy, a subaortic systolic pressure gradient at rest estimated at 80 mm Hg, and mild mitral regurgitation. Her symptoms did not respond to the sequential administration of atenolol, verapamil, disopyramide, or the combination of atenolol and disopyramide. Although amiodarone reduced the frequency of the paroxysms of atrial fibrillation, she has required cardioversion for individual episodes and receives warfarin. HCM has been diagnosed by echocardiography in her 20-year-old daughter; her 11- and 9-year-old sons have shown no abnormalities on clinical examination. There is no history suggestive of HCM in her deceased grandparents, her living parents, or her 5 siblings. ### Explanation of the Clinical Presentation Obstruction to left ventricular outflow occurs in approximately 25% of patients with HCM. Indeed, many of the early reports of this condition occurred in patients initially believed to have congenital or valvular subaortic stenosis.1 Studies in the early 1960s revealed that the unique feature of the obstruction in HCM is its dynamic nature.2 Conditions that reduce left ventricular volume narrow the distance between the hypertrophied …

Journal ArticleDOI
TL;DR: Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization and helps recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction.
Abstract: Patel KK, Frederick B, Nakada MT, Topol EJ. Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization. Circulation 2001;104:163–167. 15. Neumann FJ, Blasini R, Schmitt C, Alt E, Dirschinger J, Gawaz M, Kastrati A, Schomig A. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998;98:2695–2701.


Journal ArticleDOI
TL;DR: Data from the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy was used to test the hypothesis that diabetes was associated with increased LV enlargement after myocardial infarction.
Abstract: Background— Diabetic patients are at increased risk for heart failure (HF) and other adverse events after myocardial infarction (MI). Left ventricular (LV) enlargement after MI is also associated with the same increased risk. We used data from the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy to test the hypothesis that diabetes was associated with increased LV enlargement after MI. Methods and Results— Four hundred twelve nondiabetic and 100 diabetic patients underwent echocardiographic assessment at baseline and 3 months, 1 year, and 2 years after MI. HF developed in 30% of diabetic and 17% of nondiabetic patients during follow-up (P<0.001). Baseline LV diastolic size, ejection fraction, and infarct segment length were similar between diabetic and nondiabetic patients. Diabetic patients demonstrated less LV enlargement between baseline and 2 years than nondiabetic patients (0.9±11.1 cm2 versus 3.8±10.9 cm2, P=0.047). In patients who developed HF, LV diastolic dilatation (10.0±12...

Journal ArticleDOI
TL;DR: Treatment with pravastatin over 5 years reduces all-cause mortality and coronary mortality in patients with and those without a history of coronary heart disease, and the size of the benefit was related principally to the baseline risk.
Abstract: Aims To assess the effects of pravastatin on all-cause mortality and cause-specific mortality and to compare the effects for patients with prior coronary heart disease with those for patients without, using pooled data from the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study, the Cholesterol and Recurrent Events (CARE) study, and the West of Scotland Coronary Prevention Study (WOSCOPS). Methods and Results 13173 patients with coronary heart disease and 6595 men with elevated cholesterol and no prior coronary disease received pravastatin, 40mg daily, or placebo for an average of 5 to 6 years. Data were analysed according to a pre-specified, published protocol. For all three trials combined, the mortality among patients assigned pravastatin was significantly lower, at 7·9%, than the 9·8% among those assigned placebo, a relative risk reduction of 20% (95% confidence interval (CI) 12–27%, P <0·0001). Active treatment was associated with a reduction in coronary mortality (24%, 95% CI 14–33%). Larger reductions in absolute risk were estimated in those with prior coronary heart disease than in those without. Conclusion Treatment with pravastatin over 5 years reduces all-cause mortality and coronary mortality in patients with and those without a history of coronary heart disease. The size of the benefit was related principally to the baseline risk.

Journal ArticleDOI
TL;DR: The goal of this study was to validate the TIMI risk score in a large unselected population of patients with UAP/NSTEMI and assess its long-term predictive value.
Abstract: The 1.4 million patients admitted with unstable angina pectoris and non‐ST-elevation myocardial infarction (UAP/NSTEMI) each year are a heterogenous population with varying risks of death and recurrent cardiac events. The Thrombolysis In Myocardial Infarction (TIMI) risk score for UAP/NSTEMI was created to better stratify patients according to easily obtainable information gathered from the initial history, electrocardiogram, and cardiac markers. 1 The TIMI risk score was derived and validated in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Non‐Q-wave Coronary Events (ESSENCE) trials and accurately predicted adverse outcomes through 14 days. It has also been applied in the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) and Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-TIMI 18 Trials. 2,3 However, because clinical trials of UAP/ NSTEMI usually select higher risk patients (with electrocardiographic changes and/or positive cardiac markers), there has been questions whether the TIMI risk score would be valid in an unselected population of patients representative of general clinical practice. The goal of this study was to validate the TIMI risk score in a large unselected population of patients with UAP/NSTEMI and assess its long-term predictive value. ••• The details of the TIMI III Registry have been previously reported. 4 Briefly, patients admitted be

Journal ArticleDOI
TL;DR: Leaders of major academic medical institutions provide guidance on the successful management of several specific points of interaction between academic medical centers and commercial entities.
Abstract: Ties between academic medical centers and commercial entities are increasing in number and magnitude. These ties have the potential to benefit the public through the development of novel diagnostic and therapeutic techniques. They can also be quite problematic, since the goals of an academic medical center and those of a commercial entity may differ in many respects. In this article, leaders of major academic medical institutions provide guidance on the successful management of several specific points of interaction.

Journal ArticleDOI
TL;DR: Thrombolysis and adjunctive/rescue PCI achieved equal rates of epicardial flow in patients with and without diabetes, however, diabetic patients had less complete ST-segment resolution, suggesting impaired microvascular flow.


Journal ArticleDOI
TL;DR: In this paper, the authors defined the prognostic value of serum myoglobin in patients with non-ST-elevation acute coronary syndromes (ACS) and established that myoglobin may be useful for the early diagnosis of myocardial infarction (MI).

Journal ArticleDOI
TL;DR: Smokers have lower mortality after AMI than non-smokers, due in large part to lower clinical risk profiles and faster epicardial blood flow after thrombolysis, and microvascular injury does not appear to play a major role in the lower mortality risk among smokers.
Abstract: Background: Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), smokers have a paradoxically lower mortality after thrombolysis for AMI than non-smokers. We determined the clinical risk profiles and coronary flow characteristics of patients in the TIMI trials according to smoking status, focusing on microvascular flow. Methods: Among 2,573 patients in the TIMI 4, 10A, 10B and TIMI 14 trials, epicardial flow post-thrombolysis was measured using angiographic TIMI flow grades and the corrected TIMI frame count (CTFC). Microvascular flow was measured by TIMI Myocardial Perfusion Grade (TMPG) and, in TIMI 14, the percentage of ST segment resolution. Results: Clinically, the mean age (54 vs. 62 years), the prevalence of diabetes mellitus (11% vs. 16%) and hypertension (26% vs. 40%), and the 30-day mortality (2.6% vs. 6.2%) were lower among smokers than non-smokers (all p ≤ 0.001). Angiographically, single-vessel disease (48% vs. 40%) and non-left anterior descending infarct arteries (65.4% vs. 60.8%) were more common among smokers (both p ≤ 0.01). Epicardial TIMI grade 3 flow was achieved more often in smokers than non-smokers (61% vs. 56%) and the CTFC was faster (34 vs. 37 frames/sec, both p ≤ 0.01), especially in LAD lesions. However, the frequency of normal microvascular flow (TMPG 3) was similar among smokers and non-smokers (24% vs. 29%, p = 0.16), as was the frequency of complete ST segment resolution (50% vs. 46%, p = 0.29). Conclusions: Smokers have lower mortality after AMI than non-smokers, due in large part to lower clinical risk profiles and faster epicardial flow. Differences in tissue-level perfusion do not appear to contribute to lower mortality in smokers. Abbreviated Abstract. After acute MI, active smokers have lower acute mortality than non-smokers that appears to be largely explained by their healthier risk profiles, less extensive coronary disease, and faster epicardial blood flow after thrombolysis. Microvascular injury does not appear to play a major role in the lower mortality risk among smokers.

Journal ArticleDOI
TL;DR: The trend toward a lower rate of death or nonfatal MI in the bivalirudin group is consistent with a therapeutic effect of the drug and is consistentwith other trials of bivalIRudin in patients with acute coronary syndromes.

Journal ArticleDOI
19 Jun 2002-JAMA
TL;DR: Results from an observational cohort study that indicate no difference in mortality and cardiovascular outcomes among patients with ACS who initiated statin treatment prior to hospital discharge and patients who did not receive statins are presented.
Abstract: CAN OBSERVATIONAL DATA SUBSTITUTE FOR RANDOMized controlled trials for developing treatment recommendations and initiating public health interventions? This question arises from the article by Newby and colleagues on the early initiation of statins in patients with acute coronary syndromes (ACS), reported in this issue of THE JOURNAL. The authors present results from an observational cohort study that indicate no difference in mortality and cardiovascular outcomes among patients with ACS who initiated statin treatment prior to hospital discharge and patients who did not receive statins. Almost 2 million patients with ACS are discharged from US hospitals each year. Since these patients are at high risk for recurrent events, secondary prevention is an important medical challenge. Randomized clinical trials (RCTs) have shown the benefits of aspirin, -blockers, and clopidogrel in these patients. Furthermore, there is evidence that administration of these agents prior to hospital discharge reduces recurrent event rates. Large RCTs have indicated that initiation of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) months to years following an ACS event is effective for secondary prevention. Recently, attention has focused on the optimal time to commence statin therapy. Several observational studies, among them 2 large studies comprising some 40000 patients, found that early statin therapy was associated with lower rates of death. In addition, the results from 2 RCTs, although not definitive, yielded consistent results. Consequently, a strong momentum is building to recommend routine, early initiation of statin therapy in post-ACS patients. Indeed, such therapy is recommended in contemporary practice guidelines. The retrospective cohort study using data from the Sibrafiban vs Aspirin to Yield Maximum Protection From Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) ACS trials strikes a dissonant note. In contrast to the previous studies, the report by Newby et al indicates no benefit from early initiation of statin therapy for any clinical end point, except stroke, for which statins appeared protective. How should the results from the SYMPHONY populations be interpreted and how can the differences between this and the previously reported studies be explained? One possible reason for the surprising findings is that the fractions of patients in the 2 SYMPHONY trials for whom statins were started in the hospital as well as those for whom revascularization was performed were much larger than in the other 2 observational studies. Perhaps the analysis reported by Newby and colleagues signals that statins simply do not offer a significant additional benefit in the presence of revascularization therapy in relatively low-risk patients. Other possible explanations for the different results obtained by the various studies are measurement error and confounding. Any results, whether from observational studies or RCTs can be distorted by measurement error. Measurement error may have affected the ascertainment of statin use, the diagnosis of ACS, and all clinical covariates. Furthermore, observational studies are especially vulnerable to confounding. Although analytic techniques can address the control of measured confounders, unmeasured confounders remain an omnipresent threat to the validity of nonrandomized research. Mismeasurement of a confounder, such as low-density lipoprotein cholesterol (LDL-C) level, might not create a problem if the physician decided treatment based on the mismeasured variable. Nevertheless, any discrepancy between the value of a confounder used by the physician and that used in the analysis could lead to residual confounding. To overcome the lack of randomization in their cohort, Newby et al used propensity scores to account for imbalances in baseline characteristics. In the 2 other large observational studies on this issue available to date, propensity scores were also used. Propensity scores have become a popular tool in pharmacoepidemiology. Of particular con-

Journal ArticleDOI
TL;DR: The influence of time from symptoms on epicardial flow and STRES reinforces the need for increased efforts to reduce treatment delays in patients with ST elevation MI and suggests phase II trials evaluating new drug combinations should consider using a randomization scheme that stratifies patients based on infarct location and time from Symptoms.
Abstract: Background When evaluating new reperfusion regimens for ST elevation MI, it is important to adjust for factors that influence the likelihood of achieving normal epicardial flow and complete ST resolution. Methods and Results A total of 610 patients from TIMI 14 contributed to the angiographic analyses. The electrocardiographic analyses were based on 544 patients from TIMI 14 and 763 patients from InTIME-II. For each hour from onset of symptoms to initiation of pharmacological reperfusion, the odds of achieving TIMI3 flow at 90min or complete ST resolution at 60–90min decreased significantly ( P =0·03). Anterior location of infarction was associated with a reduction in the odds of achieving TIMI3 flow or complete ST resolution. The use of abciximab as part of the reperfusion regimen significantly increased the odds of TIMI3 flow ( P =0·01) and ST resolution ( P <0·001). The fibrinolytic administered (alteplase, reteplase, lanoteplase) did not influence the odds of TIMI3 flow or ST resolution after adjusting for time to treatment, infarct location, and use of abciximab. Conclusions The influence of time from symptoms on epicardial flow and STRES reinforces the need for increased efforts to reduce treatment delays in patients with ST elevation MI. The significant benefits of abciximab with respect to facilitation of epicardial and myocardial reperfusion are evident even after adjusting for time to treatment and infarct location. To adjust for determinants of success of reperfusion regimens, phase II trials evaluating new drug combinations should consider using a randomization scheme that stratifies patients based on infarct location and time from symptoms.

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TL;DR: The development of the coronary care unit in the early 1960s with continuous electrocardiographic monitoring and prompt external defibrillation by a trained team eliminated almost all early arrhythmic deaths in patients treated in such units, thereby reducing the early mortality by half, leaving pump failure associated with large infarction as a major challenge in cardiology.
Abstract: In the second half of the 19th Century, physiologists observed that ligation of a major coronary artery in the dog was immediately fatal. During that era, pathologists occasionally encountered thrombosis of such vessels and acute myocardial infarction (AMI) at autopsy, and considered this combination of findings to be quite uncommon and uniformly fatal. At the dawn of the twentieth century, Krehl, a Viennese physician, challenged these beliefs and reported that coronary thrombosis was actually compatible with survival [1]. In 1910, Obrastov and Strazheske [2], two Russian physicians, and in 1912, Herrick, a Chicago physician [3], described the clinical features of AMI, related them to the pathologic findings and distinguished AMI from angina pectoris. Herrick also adapted the then new technique of electrocardiography to the premorbid diagnosis of AMI, considered at the time to be a very uncommon condition. By the middle of the 20th Century, during my clinical training in internal medicine and cardiology at New York University, New York's Mount Sinai Hospital, and Johns Hopkins, it was clear that rather than being a curiosity, AMI was, in fact, the most common cause of death in the United States and western Europe. Arrhythmias and pump failure were the two major reasons for both the very high early (approximately 30% in 30 days) and late (approximately 50% in 1 year) mortality in patients who reached the hospital. The development of the coronary care unit in the early 1960s with continuous electrocardiographic monitoring and prompt external defibrillation by a trained team eliminated almost all early arrhythmic deaths in patients treated in such units, thereby reducing the early mortality by half [4], leaving pump failure associated with large infarction as a major challenge in cardiology. In 1951, as a medical student at New York University and Bellevue Hospital, I … * Tel.: +1-617-732-8989; fax: +1-617-975-0955. ebraunwald{at}partners.org

Journal ArticleDOI
TL;DR: The Braunwald classification of UAP predicts prognosis with secondary U AP, post-MI UAP, and patients with pain at rest who have a higher risk for death or recurrent cardiac events.
Abstract: The unstable angina pectoris (UAP) classification proposed by Braunwald in 1989, although often used, has never been validated in a large, prospective multicenter study in which all subgroups of patients were included Patients with UAP or non-ST-elevation myocardial infarction (NSTEMI) were enrolled in the Thrombolysis In Myocardial Ischemia III Registry and classified according to the Braunwald classification for UAP Clinical end points were compared at 6 weeks and 1 year Of 3,318 patients, those with primary UAP had lower rates of recurrent myocardial infarction (MI) or death when compared with patients with secondary UAP and post-MI UAP at 6 weeks (41% vs 64% vs 134%, respectively; p <0001) and 1 year (97% vs 167% vs 197%; p <0001) Recurrent ischemia at 6 weeks followed the same gradient (132% vs 185% vs 208%; p <0001) Patients with secondary UAP had similar extent of disease at angiography as primary UAP Patients with nonresting UAP had lower rates of death or MI than patients with UAP at rest (30% vs 56%, p = 0011 at 6 weeks, and 82% vs 125%, p = 0004 at 1 year) Patients with ST-segment deviation and those who had received prior antianginal medical treatment also had worse outcomes Thus, the Braunwald classification of UAP predicts prognosis with secondary UAP, post-MI UAP, and patients with pain at rest who have a higher risk for death or recurrent cardiac events Given their high risk for adverse events, patients with secondary UAP should be treated aggressively

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TL;DR: Use of the TIMI risk score for UA/NSTEMI revealed a progressive, statistically significant increase in the rate of events after leaving the hospital as the patients' baseline level of risk increased.