E Braunwald

..Cumulatively, it seems likely that the clinical advances emerging from ongoing research will, in the foreseeable future, reduce the number of deaths in the industrialized world from cardiovascular disease...

..TIMI is currently conducting 7 large trials worldwide on novel agents designed to reduce the morbidity and mortality of a variety of cardiovascular disorders...

..Research and practice are increasingly conducted in cardiovascular centres and institutes. It is likely that in the future, a greater emphasis will be placed on prevention, which will be enhanced by genetic information...

..Those at low risk should continue to receive intensive antiischemic and antithrombotic therapy. At discharge, patients should receive intensive lipid-lowering therapy with high doses of a statin, as tolerated...

..A plan for the testing of these interventions in patients with acute myocardial infarction is described...

..The ideal platelet function test for clinical practice would be rapid, easy-to-use, inexpensive, and reliable...

..We conclude that the hemodynamic status and neurohumoral background at the time of coronary occlusion and for at least 3 hr thereafter can alter the extent and severity of myocardial ischemic injury and myocardial necrosis...

..Patient nonadherence to treatment and premature discontinuation and underutilization of antiplatelet therapies by physicians remain important clinical problems with potentially dire consequences...

..The article ends with some general comments on conducting research and the rewards that can come with this activity...

..I focus attention on the sociological aspects of the Atlantic City meetings and the critically important role these meetings played in the evolution of academic medicine during the third quarter of the 20th century...

..Lower-risk patients should undergo early noninvasive stress testing. An intensive program of secondary prevention is mandatory and should be begun before hospital discharge...

..Given their high risk for adverse events, patients with secondary UAP should be treated aggressively...

..Results from these studies could cause a paradigm shift toward individualized antiplatelet therapy, improving predictability of platelet inhibition, and diminishing the likelihood for hyporesponsiveness...

..Currently, it appears that the use of GP IIb/IIIa antagonists might be most beneficial in high-risk ACS patients scheduled to undergo PCI, who demonstrate non-ST-segment elevation myocardial infarction and elevated troponin levels...

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..Aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors, the 3 major pharmacologic approaches to persistent platelet activation, target various levels of the hemostatic pathways and thrombus formation...

..The recognition of this fourth and last major feature in 1959 makes 2009 the golden anniversary year marking completion of the description of the major features of HOCM...

..Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non-Q-wave myocardial infarction (UA/NQMI)...

..There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation...

..We sought to determine whether the rapid bedside assay for troponin T identified patients at risk for a more complicated hospital stay and a higher rate of adverse clinical events...

..The availability of a reliable, noninvasive serum marker of reperfusion may permit early identification of patients with occlusion after thrombolysis who might benefit from further interventions...

..reteplase when administered in combination with abciximab were associated with higher TIMI 3 flow rates than reported previously for reduced doses of reteplase without abciximab and were at least as high as for full dose reteplase alone..

..We studied whether inflammation after myocardial infarction (MI) is a risk factor for recurrent coronary events and whether randomized treatment with pravastatin reduces that risk...

..Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition might provide an additional reduction in recurrent events...

..ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab...

..We determined whether the combination of abciximab plus reduced-dose tPA provided additional benefit in terms of myocardial reperfusion, as evidenced by greater resolution of ST elevation...

..Complex multivariable models identify independent predictors and quantify their relative contribution to mortality risk but are too cumbersome to be readily applied in clinical practice...

..A prospectively planned meta-analysis was performed to provide a more precise estimate of the effects of enoxaparin on multiple end points...

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..Although LDL lowering has been shown to reduce recurrent coronary events in patients with coronary heart disease, little direct information is available on the extent of LDL lowering required to achieve this outcome...

..We evaluated the combination of a baseline myoglobin assay and early (60- to 90-minute) ST resolution for risk stratification after ST-segment elevation myocardial infarction...

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..These findings have important implications in the design and interpretation of international studies, identify under- and over-utilized therapies, and support further study of treatments with marked worldwide variations...

..The optimal heparin dose as an adjunct to fibrinolysis and its role in causing intracranial hemorrhage (ICH) is unclear...

..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...

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..However, these studies were performed prior to the widespread use of platelet glycoprotein IIb/IIIa inhibitors and intracoronary stents...

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..In conclusion, compared with patients with ACS without previous CABG, those with previous CABG have a higher risk for adverse cardiac events and may derive similar benefit from intensive statin therapy...

..Patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events...

..e., TIMI 3 flow at 90 minutes) who did not undergo revascularization (p = 0.02). Thus, early PCI following AMI is associated with excellent outcomes. Randomized trials of an early invasive strategy following thrombolysis are warranted...

..We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI)...

..These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI...

..A variety of imaging modalities have implicated impaired myocardial perfusion in the pathogenesis of acute coronary syndromes (ACSs)...

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..We sought to determine whether STRes provides incremental risk stratification to the TIMI risk score...

..We sought to evaluate the effect of nonemergent PCI on mortality among patients with STEMI treated with fibrinolytic administration and the consequence of clopidogrel pretreatment on this effect...

..Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals but have not been assessed with respect to prognosis in patients with acute coronary syndrome...

..Early restoration of epicardial flow before primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been associated with improved clinical outcomes...

..Women and men enrolled in the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial of unstable angina and non-Q wave myocardial infarction (MI) were evaluated to determine gender differences in characteristics and outcome...

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..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)...

..RPR 109891 is a modified tetrapeptide glycoprotein IIb/IIIa inhibitor available in intravenous and oral formulations. Two phase II dose-ranging studies were performed to investigate pharmacodynamics and safety in acute coronary syndromes...

..A low 12-hour myoglobin level (< or = 239 ng/mL in this substudy) identifies such patients at low risk and could potentially assist in early risk stratification and triage after ST-segment elevation myocardial infarction...

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..We sought to assess the influence of baseline lipid levels on coronary event rates and the effectiveness of pravastatin therapy in the Cholesterol And Recurrent Events (CARE) study...

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..Available models for predicting mortality in STEMI include up to 45 variables, but have consistently shown advanced age, increased heart rate, and decreased blood pressure to be among the strongest predictors...

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..In patients with a LAD culprit lesion, proximal lesion location is a multivariate correlate of adverse outcomes even after adjustment for coronary blood flow and other covariates...

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..MCP-1 appears to play a critical role at multiple stages in atherosclerosis, including the initiation of the fatty streak, promotion of plaque instability, and remodeling after myocardial infarction...

..Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention...

..Developed and validated in multiple clinical trials of fibrinolysis, the risk score has not been validated in a community-based population...

..Thus, the 60-minute angiographic end point appears to be a valid alternative to that at 90 minutes and may permit earlier decisions regarding post-thrombolytic intervention...

..There is increasing evidence of a link between conduit vessel stiffness and cardiovascular events, although the association has never been tested in a large post-myocardial infarction patient population...

..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...

..At 30 days, Lp-PLA2 activity is significantly lowered with high-dose statin therapy and is associated with an increased risk of CV events independent of C-reactive protein and LDL cholesterol levels...

..These data support the value of combining markers of hemodynamic stress with traditional approaches to risk assessment in acute myocardial infarction...

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..There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction...

..Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown...

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..Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose...

..These findings likely explain in part the particular benefit of potent antithrombin and antiplatelet agents among patients with higher risk scores...

..0 vs 5.1 mg/L, p <0.001). CRP was associated with adverse cardiovascular outcomes in smokers and nonsmokers, even when adjusted for the presence of pulmonary disease...

..To investigate the relationship between diabetes and inflammation and the potentially synergistic relationship between hyperglycaemia and inflammation on clinical outcomes in non ST-elevation ACS...

..Patients who experience late-onset HF have a 10-fold increased risk of death compared with other MI survivors. Baseline characteristics can risk stratify patients at high risk of subsequent HF...

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..On the basis of these findings, 1 death was prevented for every 95 patients treated with high-dose statin therapy for 2 years. The results of this pooled analysis provide further evidence for early intensive statin therapy after ACS...

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..2% vs 3.2% to 3.6% for WBC count < 10,000; p < 0.000). With its simplicity and widespread availability, WBC count could serve as a simple, inexpensive, new tool for risk stratification in acute coronary syndromes...

..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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..Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma...

..In stable patients, intensive statin therapy provides long-term reduction in clinical events when compared with standard therapy. Thus, ACS patients should be started in-hospital and continued long-term on intensive statin therapy...

..We studied the angiographic and electrocardiographic responses to thrombolytic agents in patients with diabetes; in particular ST-segment resolution as a measure of microvascular flow...

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..High TRS at presentation is associated with abnormal myocardial perfusion, even after adjusting for possible confounders...

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..Notably, combined assessment of sCD40L with cTnI complements prognostic information for death and MI...