Search

Introduction The efficacy and safety of the oral factor Xa inhibitor edoxaban compared to warfarin stratified by CHA2DS2VASc scores have not been described. Methods The ENGAGE AF-TIMI 48 trial randomized patients with atrial fibrillation to once-daily edoxaban or warfarin. We classified patients based on CHA2DS2VASc score and compared pharmacokinetics (edoxaban concentration), pharmacodynamics (anti-factor Xa [FXa] with edoxaban, time-in-therapeutic range for warfarin), efficacy (stroke or systemic embolism [SSE]), safety (major bleeding [MB], intracranial hemorrhage), and cardiovascular mortality, for the approved edoxaban regimen vs warfarin. Results The distribution CHA2DS2VASc score were:≤3, N = 4159 (29.6%); 4, N = 4066 (28.9%); 5, N = 3165 (22.5%); and ≥6, N = 2681 (19.1%). Increasing rates of SSE (1.05 to 2.99%/year) and MB (2.27 to 4.66%/year) were observed in the warfarin arm as the CHA2DS2VASc score increased. The hazard ratios per unit increase of CHA2DS2VASc score were 1.29 (1.21-1.38) and 1.26 (1.17-1.36) for SSE, and 1.20 (1.13-1.27) and 1.19 (1.12-1.27) for MB, with warfarin and edoxaban, respectively. Time-in-therapeutic range in warfarin-treated patients was similar and high (median 68%-69%) across CHA2DS2VASc scores, whereas edoxaban trough concentration, exogenous anti-FXa activity and %inhibition of endogenous FXa were higher at increasing CHA2DS2VASc scores. Edoxaban reduced SSE, MB, intracranial hemorrhage, and cardiovascular mortality vs warfarin to a similar degree across the range of CHA2DS2VASc scores (P-int = 0.90, 0.96, 0.21, and 0.37, respectively). Because of higher event rates the number of events prevented with edoxaban tended to be greater in patients with higher CHA2DS2VASc scores. Conclusion The benefit and safety of edoxaban versus warfarin is maintained across CHA2DS2VASc scores. While the relative risk reductions remain similar, edoxaban provides incrementally larger absolute reductions in outcomes over warfarin in patients with higher CHA2DS2VASc scores.

A strategy using coronary artery calcium (CAC) screening to refine coronary heart disease risk assessment in moderately high risk (MHR) subjects (10-year risk 10%-20%) has been suggested. The potential impact of this strategy is unknown.Coronary artery calcium screening strategies focused on MHR subjects were modeled in 2,610 subjects aged 30 to 65 years undergoing Framingham risk scoring and CAC assessment in the Dallas Heart Study. The proportions of subjects eligible for imaging and reclassified from MHR to high risk (HR) (10-year risk20%) based upon CAC scores were determined.Only 1.0% of women and 15.4% of men were at MHR by Framingham risk scoring and thus eligible for imaging, and0.1% and 1.1% respectively, changed from MHR to HR using a CAC thresholdor = 400. Coronary artery calcium imaging targeting MHR subjects was also relatively inefficient (100 women, 14.3 men scanned per subject reclassified). Restricting to an older age range (45-65 years) or expanding the MHR group to 6% to 20% risk had virtually no impact on risk assessment in women. In a secondary analysis, a proposed imaging strategy targeting promotion of subjects from lower risk to MHR was more efficient and had greater yield than current recommendations targeting promotion from MHR to HR.Coronary artery calcium screening strategies focused on MHR subjects will have a negligible impact on risk assessment in women and a modest impact in men. Further studies are needed to optimize the use of CAC screening as an adjunct to coronary heart disease risk assessment, especially for women and those at seemingly lower risk.

Background Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate. Methods In the PROVE IT–TIMI 22 study, 4162 patients with an acute coronary syndrome within the preceding 10 days were randomly assigned in a 1:1 fashion to pravastatin 40 mg or atorvastatin 80 mg daily. The primary efficacy outcome measure was the time from randomization until the first occurrence of a component of the primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, or stroke. Results At 30 days, there was a trend for less occurrence of the primary end point in patients randomized to atorvastatin compared with pravastatin, irrespective of whether they were taking clopidogrel. This becomes significant at 2-year follow-up in clopidogrel-treated patients (21.66 % vs 26.18% P = .0091). There was no evidence of interaction in the clopidogrel/no clopidogrel subgroup for the primary end point (interaction P = .65) or the components of the composite. Conclusion In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel.

The aim of this study was to determine correlates of acute/subacute coronary stent thrombosis among unselected patients treated in the era of routine dual antiplatelet therapy and specifically to investigate the influence of prophylactic administration of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors and use of clopidogrel versus ticlopidine on the development of coronary stent thrombosis (ST).Because of a relative infrequency of ST events and relatively uniform practice patterns within randomized trials, previous studies have had a limited ability to address whether the use of different antiplatelet regimens at the time of coronary stenting is associated with differences in ST.We performed a multicenter, case-control study to evaluate clinical, angiographic, and pharmacologic/procedural correlates of ST. Between 1996 and 2000, all cases of angiographically-confirmed ST (n = 145) among patients receiving dual antiplatelet therapy were identified from 10 participating clinical sites and were matched with a control without ST randomly selected from the same institution.Multivariable conditional logistic regression identified higher pre-procedure platelet count, stenting for acute myocardial infarction, use of a coil or self-expanding stent, and overt angiographic thrombus prior to the procedure, as independent predictors of ST (all P.05). After adjusting for these factors, the use of clopidogrel (vs ticlopidine) was independently associated with an increased risk of ST (OR 2.1, 95% CI 1.0-4.1, P = .04). The use of prophylactic glycoprotein IIb/IIIa inhibitors was not associated with reduced ST in the overall analysis, but appeared to confer some protection against ST within the first 24 hours post procedure (OR 0.5 [95% CI 0.2-1.1] for ST during first day, OR 1.7 [95% CI 0.7-4.3] for ST on subsequent days).Both biologic and pharmacologic factors are independently associated with acute/subacute ST. The association between clopidogrel use (vs ticlopidine) and increased ST in this analysis requires confirmation in adequately powered clinical trials and suggests a potential role for newer and more potent antiplatelet agents.

Background Atrial fibrillation (AF) is a major risk factor for stroke and systemic embolism. Trials comparing warfarin with non–vitamin K oral anticoagulants (NOACs) have demonstrated that, when compared with warfarin, the NOACs are at least as effective in preventing stroke, although detailed analyses characterizing systemic embolic events (SEEs) are lacking. Methods and results We performed a prespecified analysis in 21,105 patients with AF enrolled in the ENGAGE AF-TIMI 48 trial, which compared 2 once-daily regimens of edoxaban with warfarin for the prevention of stroke and SEE. Of 1,016 patients who met the primary end point, 67 (6.6%) experienced an SEE of which 13% were fatal. Of 73 total SEEs (including recurrent events), 85% involved the extremities, and 41% required a surgical or percutaneous intervention. There were 23 (0.12%/year) SEEs with warfarin versus 15 with higher dose edoxaban (0.08%/year; hazard ratio vs warfarin 0.65; 95% CI 0.34-1.24; P = .19) and 29 with lower dose edoxaban (0.15%/year; hazard ratio vs warfarin 1.24; 95% CI 0.72-2.15; P = .43). In a meta-analysis of 4 warfarin-controlled phase 3 AF trials, NOACs significantly reduced the risk of SEE by 37% (relative risk 0.63; 95% CI 0.43-0.91; P = .01). Conclusion Although considerably less frequent than stroke, systemic embolism is associated with significant morbidity and mortality in patients with AF. Although the overall number of events was too small to show a significant difference in the risk of SEE between edoxaban and warfarin, a meta-analysis of all the NOAC trials demonstrates that NOACs significantly reduce the risk of SEE compared with warfarin.

Background 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. Methods We hypothesized that early administration of the glycoprotein IIb/IIIa inhibitor eptifibatide in the emergency department (ED) would yield superior epicardial flow and myocardial perfusion before primary PCI compared with initiating eptifibatide after diagnostic angiography in the cardiac catheterization laboratory (CCL). Three hundred forty-three patients with STEMI were randomized to either early ED eptifibatide (n = 180) or CCL eptifibatide (n = 163). Results The primary end point (pre-PCI corrected TIMI frame count) was significantly lower (faster flow) with early eptifibatide (77.5 ± 32.2 vs 84.3 ± 30.7, P = .049). The incidence of normal pre-PCI TIMI myocardial perfusion was increased among patients treated in the ED versus CCL (24% vs 14%, P = .026). There was no excess of TIMI major or minor bleeding among patients treated in the ED versus CCL (6.9% [12/174] vs 7.8% [11/142], P = NS). Conclusion A strategy of early initiation of eptifibatide in the ED before primary PCI for STEMI yields superior pre-PCI TIMI frame counts, reflecting epicardial flow, and superior TIMI myocardial perfusion compared with a strategy of initiating eptifibatide in the CCL without an increase in bleeding risk.

Troponin testing is useful for evaluating patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker.Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative. A score predicting late TnI rise in TIMI IIIB was developed using these factors and validated among patients in the GUSTO IIA study.Of 1342 subjects in TIMI IIIB, 200 (14.9%) were negative at baseline, but developed an elevated TnI (or = 0.4 ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified: ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P.001), presentation8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P.001), no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P = .001), no prior beta-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008), unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation, presentation8 hours from symptoms, and no prior percutaneous coronary intervention were given a score of 2 points, whereas a score of 1 point was assigned to the other factors. Among baseline TnI-negative patients, a rising score was paralleled by an increasing prevalence of late TnI rise from 0% (with a score of 0) to 69% (with a score of 9) (P.001). In confirmation, the score was able to similarly predict late troponin T rise among 855 patients in the GUSTO IIA study (P.0001).Development of late troponin rise is common in non-ST-segment elevation acute coronary syndromes. Six easily ascertained variables may be used to identify those at higher risk for late rise in troponin levels after an initially negative presentation.

Background Early cardiac catheterization has been shown to improve outcomes in patients with non–ST-elevation acute coronary syndromes but not yet in those with ST-elevation myocardial infarction (STEMI). The benefit of catheterization in both syndromes may depend on patient risk for adverse clinical outcomes. Methods We analyzed the relation between inhospital catheterization and subsequent clinical outcomes based on risk profile in 8286 patients in the OPUS-TIMI 16 Trial of patients with acute coronary syndromes. Using baseline clinical characteristics, patients were stratified into low-, intermediate-, and high-risk groups. The primary end point was 10-month mortality. The STEMI, non-STEMI (NSTEMI), and unstable angina subgroups were analyzed separately. Results Inhospital cardiac catheterization was performed in 44% of patients. Mortality rates at 10 months were 1.3%, 2.2%, and 11.3% in the low-, intermediate-, and high-risk groups, respectively. Inhospital cardiac catheterization was associated with a trend to lower mortality among the high-risk patients with STEMI (hazard ratios [HR] 0.57, 95% CI 0.33-1.01, P = .052) and NSTEMI (HR 0.65, 95% CI 0.39-1.07, P = .088) but not in those with unstable angina (HR 0.95, 95% CI 0.63-1.43, P = .82). Catheterization was not associated with any significant difference in mortality in the low-risk or intermediate-risk group. The differences among high-risk patients persisted after adjusting for baseline characteristics; inhospital catheterization was associated with significantly lower mortality in high-risk patients with ST and non-ST myocardial infarction (HR 0.65, 95% CI 0.45-0.95, P = .03). Conclusions Inhospital cardiac catheterization is associated with lower mortality in high-risk patients and no difference in mortality in low-risk and intermediate-risk patients after STEMI and NSTEMI. These data support the hypothesis that high-risk patients with either STEMI or NSTEMI may benefit from an early invasive strategy. New prospective randomized trials are warranted, particularly in the STEMI population.

Background More complete ST-segment resolution (ST res) in acute myocardial infarction (MI) has been associated with better epicardial and myocardial reperfusion as assessed with the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and the TIMI myocardial perfusion grade (TMPG), respectively. However, no data exist comparing the speed of ST resolution on continuous electrocardiogram (ECG) monitoring with the TMPG on coronary angiography. We hypothesized that delayed ST res is associated with impaired TMPGs. Methods Continuous 12-lead ECG recordings and 60-minute angiographic data were analyzed in 120 patients with acute MI who received tenectaplase monotherapy or combination therapy with low-dose tenectaplase and eptifibatide in the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial. Results More rapid ST res on continuous ECG monitoring was associated with improved TMPGs on coronary angiography performed 60 minutes after study drug administration. For TMPG 3, the median time to ST resolution was 53 minutes. For TMPG 2, 1, and 0, the corresponding times were 64 minutes, 80 minutes, and 106 minutes, respectively ( P = .01 for trend). Likewise, more rapid ST res was also associated with faster epicardial flow. For TFG 3, the median time to ST resolution was 46 minutes, compared with 109 minutes for TIMI flow grades 0 to 2 ( P = .001). The corresponding times for a corrected TIMI frame count ≤40 versus >40 were 52 minutes and 112 minutes, respectively ( P Conclusions Although the static ECG has been associated with epicardial and myocardial blood flow in the past, this study extends these observations to demonstrate that more rapid ST res on continuous ECG monitoring is associated with improved myocardial perfusion after thrombolytic administration.

Background Successful reperfusion after acute ST-elevation myocardial infarction improves prognosis. Among the different electrocardiographic markers of reperfusion, sum ST resolution is considered the hallmark of reperfusion, but is cumbersome to use. Methods To assess the usefulness of a single lead ST resolution at 90 minutes after fibrinolysis compared with the sum ST resolution in predicting Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, we used prospectively collected data from the Limitation of Myocardial Injury Following Thrombolysis in Acute Myocardial Infarction (LIMIT-AMI) study. All patients had electrocardiograms recorded at presentation and 90 minutes and a coronary angiogram 90 minutes after fibrinolysis. Results Infarction artery patency was assessed in 238 patients with 4 different ST resolution criteria: single lead ST resolution ≥50% and ≥70% and sum ST resolution ≥50% and ≥70%. The most sensitive criteria for TIMI grade 3 flow was single lead ST resolution ≥50% (sensitivity rate, 70%; specificity rate, 54%), whereas sum ST resolution ≥70% was most the specific criteria (sensitivity rate, 45%; specificity rate, 79%). The proportion of patients with TIMI grade 3 flow was similar in all 4 ST resolution groups ( P = .84). Pre-discharge infarction size and ejection fraction were also similar. No single lead or sum lead measure of ST resolution was significantly associated with an increased risk of death, heart failure, or reinfarction. Conclusion We propose that single lead ST-resolution ≥50% as an optimal electrocardiographic indicator for successful reperfusion 90 minutes after fibrinolysis. This simple electrocardiographic measure should be combined with bedside clinical and hemodynamic assessment to optimize decision making after fibrinolysis.

Background Patients with diabetes are at increased risk of death after acute myocardial infarction, independent of other baseline risk factors and more severe coronary artery disease. 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. Methods Angiography was performed in 2588 patients at 90 minutes after thrombolytic agent administration as well as after percutaneous coronary intervention (PCI) in the Thrombolysis In Myocardial Infarction (TIMI) 4, 10A, 10B, and 14 trials. Electrocardiographic parameters were assessed at baseline and at 90 minutes in the TIMI 14 trial. Results Compared with those without diabetes, patients with diabetes (347/2588 [13.4%]) were older, more often female, heavier, and less often smokers, and they had higher systolic blood pressure on admission. At angiography, they more frequently had 3-vessel disease, well-developed collateral vessels, more distal culprit lesions, and smaller reference segment diameters. In the infarct-related artery, there was no relationship between diabetes and TIMI 3 flow at 90 minutes (55.4% vs 59.0% without diabetes) or after PCI, (83.7% vs 84.2%, both P = NS). Corrected TIMI frame counts were also similar at both time points. However, there was less frequent complete ST-segment resolution among diabetic patients after thrombolysis (38.6% vs 49.2%, adjusted P =.04). Conclusion 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. Abnormal microvascular flow may contribute at least in part to the poorer outcomes observed in patients with diabetes and acute myocardial infarction. (Am Heart J 2002;144:649-56.)

Background and Objectives Slower blood flow in the setting of acute myocardial infarction (MI) has been related to adverse outcomes, but the relationship of coronary blood flow after percutaneous transluminal coronary angioplasty (PTCA) in the setting of acute coronary syndromes to adverse outcomes and restenosis has not been well described. We sought to evaluate the correlates of pre- and post-PTCA coronary blood flow to shed light on potential modifiable determinants. Methods The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 hours of occurrence of either unstable angina pectoris or acute MI. Coronary blood flow was assessed with the corrected TIMI frame count (CTFC), and clinical outcomes were assessed at 30 days. Results In addition to tighter and longer minimum lumen diameters (MLDs), the multivariate correlates of slower flow before PTCA also included the presence of thrombus, collaterals, left coronary artery lesion location, acute MI, and >8F catheter size. As well as the above variables, type C and D dissection grades were related to slower post-PTCA CTFC. Death, or the composite of death/MI/coronary artery bypass graft at 30 days, was more frequent among patients with slower post-PTCA CTFCs and those with post-PTCA thrombus. In a multivariate model correcting for reference segment diameter and MLD, the post-PTCA CTFC was an independent predictor of late lumen loss and the follow-up MLD at 6 months. As a single index that integrates functional and anatomical aspects of the post-PTCA results, the ratio of CTFC/MLD was associated with death/MI by 30 days. Conclusions In addition to MLD, variables such as the presence of thrombus, left coronary artery lesion location, and dissection grade also are associated with slower coronary blood flow after PTCA. In turn, post-PTCA CTFCs were an independent predictor of late lumen loss and follow-up MLDs. Furthermore, patients who die or who sustain other adverse cardiac events have slower coronary blood flow and greater thrombus burden after PTCA. (Am Heart J 2002;144:130-5.)

The current standard of care for patients with non-ST-segment elevation acute coronary syndromes (ACS) includes antithrombotic therapy with aspirin and heparin. Although emerging data suggest that low-molecular weight preparations offer distinct advantages over unfractionated heparin, limited information on patient-related factors that may influence dosing, safety, and efficacy is available.The purpose of our study was the determination of the impact of patient age, sex, body weight, and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in patients with ACS.Patients enrolled in the TIMI 11A trial received a full complement of antiischemic therapy, aspirin, and enoxaparin (30 mg intravenously, followed by weight-adjusted doses of either 1 mg/kg or 1.25 mg/kg subcutaneously every 12 hours). Before and after the third and last doses, blood samples were obtained from 445 patients for measurement of anti-Xa activity. The mean apparent clearance, distribution volume, and plasma half-life were 0.733 L/h, 5.24 L, and 5 hours, respectively. Among a wide range of clinical and laboratory covariates, creatinine clearance emerged as the most influential factor on apparent clearance, area under the curve, and anti-Xa activity. Patients with marked renal impairment (creatinine clearance40 mL/min) had higher trough and peak anti-Xa activity compared with those with normal renal function and were more likely to have major hemorrhagic events.The pharmacokinetic and pharmacodynamic profiles after enoxaparin administration are consistent across a broad range of patients with ACS. Dose adjustments or anti-Xa coagulation monitoring or both will be necessary rarely in routine clinical practice, with the exception of patients with severe renal insufficiency.

Background The etiology of creatine kinase-myocardial band (CK-MB) release after percutaneous coronary intervention (PCI) remains unclear. The goal of this study was to evaluate the relationship of both epicardial and tissue level perfusion at the completion of stent placement to CK-MB release after the procedure. Given the high rates of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after PCI, we hypothesized that abnormalities in tissue level perfusion would instead explain CK-MB release. Methods Data were drawn from the angiographic substudy of the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial of eptifibatide versus placebo in patients undergoing planned coronary stent implantation. In the substudy, cinefilms of 65 patients were analyzed by an angiographic core laboratory blinded to enzymatic and clinical outcomes. Results The release of CK-MB was not associated with TIMI grade 3 flow or the corrected TIMI frame count; 100% of patients had TIMI grade 3 flow at the completion of PCI. In contrast, tissue level perfusion using the TIMI myocardial perfusion grade (TMPG) was related to postintervention CK-MB release: patients with a closed myocardium (TMPG 0/1) or delayed myocardial perfusion (TMPG 2) had an average CK-MB release 2.2 ± 2.7 times the upper limit of normal (n = 34), whereas those patients with normal myocardial perfusion (TMPG 3, n = 24) had CK-MB 0.8 ± 0.6 times the upper limit of normal (P = .01). Although no patients with TMPG 3 sustained death/myocardial infarction/urgent target vessel revascularization or thrombotic bailout, 17.7% of patients with TMPG 0/1/2 did by 48 hours (P = .037). Conclusions Impaired tissue level perfusion as assessed by the TMPG and not epicardial coronary blood flow is associated with CK-MB elevation after PCI. These data provide a pathophysiologic link between impaired tissue level perfusion, post-PCI infarction, and adverse clinical outcomes. (Am Heart J 2002;143:106-10.)

Background The Thrombolysis In Myocardial Infarction (TIMI) Study Group originally defined TIMI grade 3 flow (complete perfusion) as antegrade flow into the bed distal to the obstruction that occurs as promptly as antegrade flow into the bed proximal to the obstruction. Recently, several groups have defined TIMI grade 3 flow as opacification of the coronary artery within 3 cardiac cycles. Methods and Results On the basis of heart rate data at the time of the cardiac catheterization and the time for dye to go down the artery (TIMI frame count/30 = seconds), we estimated the number of patients who would meet the 3 cardiac cycle criterion and compared this with the number of patients with TIMI grade 3 flow by using the original definition in 1157 patients from 3 recent TIMI trials (10 A, 10B, and 14). In 74 patients without acute myocardial infarction and normal coronary arteries, the fraction of a cardiac cycle required for dye to traverse the artery was a mean of 0.93 ± 0.34 cardiac cycles (n = 74) (median 0.80, minimum 0.44, maximum 2.1, none >3.0 cycles). The mean heart rate at 90 minutes after thrombolysis in the TIMI 14 trial was 79.6 ± 16.8 beats/min (n = 194), and the duration of 3 cardiac cycles was a mean of 2.36 seconds, or a TIMI frame count of 70.8 frames. In all trials, the rate of TIMI grade 3 flow was 57.3% (n = 663/1157) with the original definition and 66.8% (n = 743/1113) with the

At least 30% of patients with non-ST-elevation acute coronary syndrome present without evidence of myonecrosis using current generation troponin assays. A new generation of research assays for troponin that offer a10-fold increase in analytical sensitivity has emerged.To perform a pilot study to evaluate the clinical sensitivity of a new ultra-sensitive nanoparticle assay for cardiac troponin I (nano-cTnI), we identified 50 patients with unstable angina (serial negative cTnI) and 50 patients with non-ST-elevation myocardial infarction with an initially negative current generation cTnI result. We measured cTnI using an assay (Nanosphere, Northbrook, IL) that can detect pg/mL concentrations of cTnI (detection-limit 0.0002 microg/L).Measured at 0, 2, and 8 hours with the nano-cTnI assay 44%, 62%, and 82% of patients with unstable angina defined by the current-generation assay had an elevated nano-cTnI result (or =0.003 microg/L, 99 th percentile decision-limit, coefficient of variation10%). In patients with definite myocardial injury (current-generation cTnIor =0.1 microg/L) but an initially negative cTnI, 72% and 98% had a nano-cTnIor =0.003 microg/L at 0 and 2 hours. No patient had a positive current-generation cTnI without an elevated nano-cTnI level.In this pilot study using a nanoparticle assay for cTnI, myocardial injury was detectable in a substantial proportion of patients presently classified as having unstable angina, suggesting that ischemia with rest pain without injury is rare. The emergence of a new generation of troponin assays has the potential to lead to new clinical applications based on enhanced analytical performance at very low concentrations of troponin.

Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate.In the PROVE IT-TIMI 22 study, 4162 patients with an acute coronary syndrome within the preceding 10 days were randomly assigned in a 1:1 fashion to pravastatin 40 mg or atorvastatin 80 mg daily. The primary efficacy outcome measure was the time from randomization until the first occurrence of a component of the primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, or stroke.At 30 days, there was a trend for less occurrence of the primary end point in patients randomized to atorvastatin compared with pravastatin, irrespective of whether they were taking clopidogrel. This becomes significant at 2-year follow-up in clopidogrel-treated patients (21.66 % vs 26.18% P = .0091). There was no evidence of interaction in the clopidogrel/no clopidogrel subgroup for the primary end point (interaction P = .65) or the components of the composite.In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel.

Background Most hospitals that perform primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in the United States exceed the recommended door-to-balloon time. There is heightened interest in identifying and eliminating factors that introduce delay. Methods We performed a key process analysis of our primary PCI program, assessed the relative contribution of individual time intervals on total ischemic time, and identified predictors of delay. Results Median times and predictors of delay within each time interval were determined for the entire STEMI cohort (“real world”) and after exclusion of patients with atypical symptoms and/or presentations of STEMI that resulted in inherent delay in diagnosis and treatment (“ideal world”). Delays in therapy were symptom onset to presentation (120 minutes [interquartile range, IQR, 60-310 minutes, ideal world] and 150 minutes [IQR 60-360 minutes, real world]; predictors of delay were peripheral vascular disease, self-transportation, daytime and weekend presentation); door-to-balloon time (118.5 minutes [IQR 96-141 minutes, ideal world] and 125 minutes [IQR 100-170 minutes, real world]; predictors of delay were female sex, previous stroke, nighttime and weekend presentation, and cardiogenic shock); and symptom onset to first balloon inflation (272 minutes [IQR 187-465 minutes, ideal world] and 297 minutes [IQR 198-560 minutes, real world]; predictors of delay were peripheral vascular disease, weekend presentation, and self-transportation). Conclusions Key process analysis of a primary PCI program identifies treatment delays unique to the hospital and the patient population it serves.

Family history of premature myocardial infarction (FHMI) may be a useful marker of cardiovascular disease (CVD) risk in young subjects, but comparisons of its implications for CVD risk factor burden, prevalent atherosclerosis, and risk awareness between young men and women have not been reported.We analyzed data from 2404 young subjects with ages 30 to 50 in the Dallas Heart Study, which is a population-based study. Family history of premature MI was defined as a first-degree relative with myocardial infarction (MI) before age 50 (men) or 55 (women). Coronary artery calcification was measured by computed tomography scan, and perceived lifetime risk of MI was assessed by questionnaire. Analyses were sex-stratified.Women with versus without FHMI had an increased composite risk factor burden (or = 2 CVD risk factors, 49.1% vs 39.1%; P.001), an association not seen in men (P = .6). Family history of premature MI was independently associated with coronary artery calcification among women (adjusted odds ratio, 2.0; 95% confidence interval, 1.0-4.1) but not among men (adjusted odds ratio, 1.7; 95% confidence interval, 0.9-3.2). A higher proportion of subjects with FHMI versus no FHMI perceived their lifetime risk of MI to be ator = average in women (59.7% vs 47.4%; P.001) and men (75.0% vs 48.3%; P = .004), with the increment greatest among men (P interaction = .02).Despite a stronger association with CVD risk factors and atherosclerosis prevalence with FHMI among young women compared with men, young women with FHMI demonstrated less CVD risk awareness and worse lifestyle choices. Family history of premature MI may be an especially useful risk assessment tool in young women, and greater efforts are needed to promote CVD risk awareness among young women with FHMI.

Background The use of routine nonemergent percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolytic therapy is unknown. 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. Methods CLARITY-TIMI 28 randomized 3491 patients with STEMI treated with fibrinolytic administration and aspirin to clopidogrel or placebo. All patients were to undergo angiography 48 to 192 hours after randomization. Percutaneous coronary intervention was performed at the discretion of the treating physician. Nonemergent PCI, which was defined as PCI that was not precipitated by recurrent myocardial infarction, was performed in 1781 patients (55.7%). Results Nonemergent PCI did not affect 30-day mortality (2.0% vs 2.3% among patients who did not undergo PCI). However, nonemergent PCI was associated with lower mortality among patients randomized to clopidogrel (1.3% vs 2.8%, P = .04) but not among those randomized to placebo (2.6% vs 1.7%, P = .25; interaction P = .025). In multivariate modeling, PCI remained associated with lower mortality among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028). Conclusion Among patients with STEMI treated with fibrinolytic administration and aspirin, nonemergent PCI was associated with lower mortality among patients pretreated with clopidogrel. These results suggest that routine nonemergent PCI is beneficial among such patients, although further confirmatory randomized studies are needed.

A variety of imaging modalities have implicated impaired myocardial perfusion in the pathogenesis of acute coronary syndromes (ACSs).We hypothesized that an abnormal TIMI myocardial perfusion grade (TMPG 0/1/2) and an impaired coronary flow reserve (CFR) as assessed angiographically using the TIMI frame count would be associated with biomarker release, ischemia on Holter monitoring, and adverse clinical outcomes in the PROTECT-TIMI 30 trial of patients with non-ST-elevation ACS undergoing percutaneous coronary intervention (PCI).The pre-PCI TMPG was correlated with the baseline as well as peak levels of troponin I (P.001) and creatine kinase-MB (P.001) and the post-PCI rise in troponin I (P = .03). The incidence of an ischemic event on Holter by 48 hours was more common among patients with an abnormal post-PCI TMPG (12.5% vs 7.0%, P = .013), and the mean normalized duration of ischemia by 24 hours after PCI on Holter monitoring trended longer among patients with an abnormal post-PCI TMPG (8.9 vs 3.2 minutes, P = .068). In multivariable analyses, an abnormal post-PCI TMPG was the strongest correlate of death, myocardial infarction, or an ischemic event by 48 hours after randomization. In contrast, the post-PCI CFR as assessed angiographically using the TIMI frame count was not associated with the baseline, peak, or absolute rise of any biomarker, Holter findings, or clinical events.An abnormal TMPG, but not an angiographic CFR, is associated with biomarker status, the occurrence and duration of Holter ischemia, and adverse clinical outcomes among patients with moderate- to high-risk non-ST-elevation ACS undergoing PCI.

Background It is uncertain how aggressively patients should be monitored and admitted to the hospital for chest pain syndromes and if the monitoring itself affects patient care, process, or outcomes. We assessed the appropriateness of care based on retrospective analysis of admission bed assignment (nonmonitored vs monitored) and Thrombolysis in Myocardial Infarction (TIMI) risk score in patients from the Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. Methods Baseline characteristics, process of care, and outcomes were compared among 2939 patients admitted to 1 of 35 hospitals in the United States. Patients were stratified into low (0-2), intermediate (3 or 4), and high (5-7) risk based on TIMI risk score. Results Among the patients, 92 (3%) were admitted to the cardiac care unit (CCU), 1602 (56%) were admitted to the telemetry unit, and 1163 (41%) were admitted to an unmonitored bed. Paradoxically, high-risk patients comprised only 1% of those in the CCU, 5% of those in telemetry, and 10% of those in nonmonitored units. Conversely, low-risk patients were 64% of those in the CCU, 53% of those in telemetry, and 42% of those in unmonitored beds. Procedures were done more often on patients admitted to nonmonitored units than those on telemetry or in the CCU irrespective of TIMI risk score. Conclusions This registry suggests that triage of patients does not routinely follow the risk-based approach suggested in the American College of Cardiology and American Heart Association guidelines and could therefore potentially lead to inefficiencies in care. Better implementation of risk stratification for acute coronary syndrome evaluation and management is necessary. (Am Heart J 2005;149:1-6.)

Lipid-lowering is effective in the prevention of cardiovascular morbidity and mortality in patients with coronary artery disease, but effective strategies for improving the implementation of these therapies are needed.In the 10,288 patients in the OPUS-TIMI 16 trial, patients were stratified by use of lipid-lowering therapy during index hospitalization and were compared for use of lipid-lowering therapy at follow-up as well as for clinical outcomes.Lipid-lowering therapy was used in 38% of patients during the index hospitalization, of which 94% were statins. At 10 months, 88% of patients who were discharged on lipid-lowering medications remained on these drugs. Conversely, only 34% of patients not discharged on lipid-lowering medications were receiving them at 10 months. Forty-one percent of patients with prior history of hyperlipidemia requiring treatment were not discharged on lipid-lowering therapy, and of these, only 51% were subsequently started on a lipid-lowering medication as an outpatient despite clear indications. Patients treated as inpatients with lipid-lowering therapy had a lower mortality rate at 10 months adjusted by propensity analysis (3.1% vs 5.1%, P.0001) than patients not treated with lipid-lowering therapy.In patients with acute coronary syndromes, the initiation of lipid-lowering therapy in the inpatient setting increases the rate of its subsequent use at 10 months, making this an important method of ensuring appropriate secondary prevention.

Background Previous reports have associated acute coronary syndromes (ACSs) with cerebrovascular disease but in general have not included long-term patient follow-up or have not analyzed ischemic and hemorrhagic cerebrovascular events separately. Methods We analyzed stroke outcomes from the OPUS-TIMI 16 study, a multicenter, randomized, placebo-controlled trial. Patients were randomized to aspirin plus either orbofiban or placebo and followed for up to 1 year. Cerebrovascular events were prospectively identified and classified by a committee of cardiologists and neurologists blinded to treatment assignment. Results During 10 months of follow-up, there were 150 (1.5%) patients with cerebrovascular events. Risk factors for ischemic stroke (n = 67) and transient ischemic attack (TIA) (n = 44) were age, prior ischemic stroke, history of hypertension, and increased heart rate. Prior ischemic stroke and history of hypertension were not risk factors for 30-day ischemic stroke or TIA. Risk factors for intracranial hemorrhage (ICH) (n = 14) were age, history of hypertension, history of TIA, and coronary angiography with evidence of coronary artery disease. Compared with placebo, treatment with orbofiban was associated with a nonsignificant increased risk of ischemic stroke or TIA (HR 1.15, 95% CI 0.76-1.74, P = .51) and ICH (HR 1.25, 95% CI 0.39-4.00, P = .70). Conclusions The overall incidence of cerebrovascular events after ACS was highest in the first 30 days then declined; risk factors for cerebrovascular events may be different in the different periods. Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA.

Background Both epicardial and myocardial perfusion have been associated with clinical outcomes in the setting of ST elevation myocardial infarction (STEMI), and the performance of adjunctive/rescue percutaneous coronary intervention (PCI) may further improve clinical outcomes after fibrinolytic administration. Methods The goal was to develop a simple, broadly applicable angiographic metric that takes into account indices of epicardial and myocardial perfusion both before and after PCI to arrive at a single perfusion grade in patients undergoing cardiac catheterization after fibrinolysis. The angiographic perfusion score (APS) is the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG; 0–3) added to the TIMI myocardial perfusion grade (TMPG; 0–3) before and after PCI (total possible grade, 0–12). Failed perfusion was defined as an APS of 0 to 3, partial perfusion was defined as an APS of 4 to 9, and full perfusion was defined as an APS of 10 to 12. The APS was evaluated in patients from the Double-blind, Placebo-contolled, Multicenter Angiographic Trial of Rhumab CD18 in Acute Myocardial Infarction (LIMIT-AMI; n=394) and Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis In Myocardial Infarction (ENTIRE-TIMI) 23 trials (n = 483), and infarct size (120–216 hours after AMI SPECT Technetium-99m Sestamibi data) was assessed in the LIMIT-AMI trial. Results The APS was associated with the incidence of death or myocardial infarction (failed, 16.7% [n = 18]; partial, 2.5% [n = 155]; full, 2.4% [n = 82]; P = .039 for trend) and larger SPECT infarct sizes (failed, median 39% [n = 10]; partial, 12% [n = 79]; and full, 8% [n = 35]; P = .002). No patient with full APS died, whereas the mortality rate was 11.1% in patients with a failed APS ( P = .03). Conclusions The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI. Partial or full angiographic perfusion scores are associated with a halving of infarct size, and no patients with full angiographic perfusion died.

Few data are available about development of congestive heart failure (CHF) in patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI). We developed and validated a risk score to predict which patients will develop CHF.A subset of 4681 patients from the Orbofiban in Patients With Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction (OPUS-TIMI 16) trial with UA/NSTEMI and without a history of CHF were included in this analysis and stratified according to the development of CHF at 10 months. A risk score was created from significant variables and validated in the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI 18) trial. B-type natriuretic peptide (BNP) was then added to the initial multivariate analysis and validated in the TACTICS-TIMI 18 trial.The incidence of CHF at 30 days was 4.9%, and at 10 months it was 5.6%. Significant variables on multivariate analysis included age65 years, heart rate100 beats/min, history of diabetes mellitus, lateral electrocardiographic changes, and history of angiographically confirmed coronary artery disease. The risk of CHF increased 10-fold across the number of risk factors (P.001). When validated in the TACTICS-TIMI 18 trial, the risk score was significantly associated with CHF at 6 months (P =.01). The median BNP value doubled across the number of risk factors (P.001 for trend). The addition of BNP to the risk score improved its discriminatory capacity.In patients with UA/NSTEMI, a simple clinical risk score can aid in assessing the risk of developing CHF. BNP adds to the predictive capacity of this risk score. This score may assist in identifying patients who warrant more careful monitoring and therapy for CHF prevention inhospital and during follow-up.

Background In the absence of thrombolytic therapy, patients with non-Q–wave myocardial infarction (MI) have previously been shown to have lower long-term mortality rates than patients with Q-wave MI. The goal of our study was to examine the angiographic and clinical differences between non-Q–wave MI and Q-wave MI in patients with ST elevation MI (STEMI) in the era of thrombolytic and combination therapy of thrombolytics plus glycoprotein IIb/IIIa inhibitors. Methods Angiography was performed 90 minutes after thrombolytic administration in the Thrombolysis in Myocardial Infarction (TIMI) 14 trial. The development of a non-Q–wave MI was assessed on electrocardiogram performed at the time of hospital discharge. Angiographic findings were assessed at an angiographic core laboratory by blinded investigators. Results The qualifying episode of ST elevation developed into a non-Q–wave MI in 36% of patients (315/878) and into a Q-wave MI in 64% of patients (563/878). In patients in whom non-Q–wave MI developed, the rate of TIMI grade 3 flow was higher, peak creatine kinase level was lower, mean left ventricular ejection fraction was greater, corrected TIMI frame counts (CTFCs) were lower (ie, faster blood flow), and chest pain duration after thrombolytic administration was shorter. Patients in whom non-Q–wave MI developed less frequently underwent a percutaneous coronary intervention (PCI), and when they did, they had faster post-PCI CTFCs and higher rates of post-PCI TIMI grade 3 flow. Patients in whom a non-Q–wave MI developed had lower rates of severe recurrent ischemia. There were no differences in 30-day or in-hospital mortality rates or recurrent MI between patients with Q-wave MI and patients with non-Q–wave MI. Conclusion After thrombolytic therapy in STEMI with or without abciximab, ejection fractions were higher, the duration of ischemia was shorter, and coronary blood flow at both 90 minutes and after PCI was faster in patients who sustained non-Q–wave MI than in patients who sustained Q-wave MI. No differences in mortality or recurrent MI rates were detected in patients who sustained a Q-wave MI and patients in whom a Q-wave MI did not evolve in the modern thrombolytic era.

Background Questions about the generalizability of randomized trial results to clinical practice have arisen because the overall mortality rate is generally lower in trials, potentially because patients who are at lower risk are enrolled. However, little is known about the characteristics of patients included in clinical trials versus those who are not included.Methods The Thrombolysis In Myocardial Infarction (TIMI) 9 Registry prospectively evaluated patients with ST-elevation myocardial infarction at 20 hospitals during the TIMI 9 trial, which compared hirudin versus heparin with fibrinolysis. We compared the characteristics, treatment, and outcomes of patients enrolled in TIMI 9B (n = 3002) with other fibrinolytic-eligible patients not enrolled in TIMI 9B (n = 296) and with those not eligible for fibrinolysis by American College of Cardiology/American Heart Association criteria, at the same centers (n = 282), with the latter groups divided by use of reperfusion therapy.Results Across the groups, ranging from those in the TIMI 9 trial to those ineligible for fibrinolysis, we observed a gradient of higher-risk baseline characteristics, lower use of reperfusion therapy, and higher mortality rates (P < .001). In addition, comparing fibrinolytic-eligible patients in TIMI 9B versus those not enrolled in the trial, the use of aspirin, β-blockers, and angiotensin-converting enzyme inhibitors was significantly higher in the TIMI 9B trial. Ineligible patients not treated with reperfusion therapy had much lower rates of use of these medications and the highest inhospital mortality rate (24%, adjusted odds ratio 2.8, P < .0001)Conclusions In this prospective registry, patients not enrolled in a clinical trial had higher risk characteristics and worse outcomes; however, they also were treated less frequently with guideline-recommended medications, which may have contributed to their higher mortality rates. (Am Heart J 2003;145:109-17.)

Background Because rescue intervention may improve the outcome of patients who fail to achieve epicardial reperfusion after fibrinolytic administration for acute ST-elevation myocardial infarction (STEMI), simple noninvasive measures of infarction-related artery (IRA) patency are needed. The sum of ST-segment resolution (sum-STRES) has a high positive predictive value (PPV) for a patent IRA, but is quite time-consuming. Methods We retrospectively developed a very simple assessment that requires only the measurement of ST-segment deviation in a single electrocardiographic lead on a single electrocardiogram (ECG) 90 minutes after fibrinolytic administration. The ECG obtained immediately before fibrinolytic administration was reviewed as a means of selecting the single lead with the greatest ST-segment deviation. The absolute magnitude of ST deviation was measured in this lead on the 90-minute ECG. Minimal ST-segment deviation (MSTD) was defined as ≤1 mm ST deviation for inferior infarctions and ≤2 mm ST deviation for anterior infarctions. We compared the predictive value of this method with established but more complex ECG methods using data from the Thrombolysis In Myocardial Infarction (TIMI) 14 trial of low-dose fibrinolytic with full-dose glycoprotein IIb/IIIa inhibition. Results Of the 604 patients with an evaluable ECG and angiographic data, 383 (63%) had MSTD. The presence of MSTD had a positive predictive value (PPV) of 91% for a patent IRA (TIMI flow grade 2 or 3). Results were similar for inferior and anterior infarctions. MSTD was a means of identifying 90% of patients with complete sum-STRES. The PPV of MSTD compared favorably with that of standard measures of ST-segment resolution, but it required only a few seconds to perform. Conclusions The presence of MSTD at 90 minutes after fibrinolytic administration indicates a very high likelihood of IRA patency. MSTD may be helpful in identifying patients with STEMI treated by means of fibrinolytics who could safely avoid emergent coronary angiography. (Am Heart J 2002;144:790-5.)

Slower blood flow in the setting of acute myocardial infarction (MI) has been related to adverse outcomes, but the relationship of coronary blood flow after percutaneous transluminal coronary angioplasty (PTCA) in the setting of acute coronary syndromes to adverse outcomes and restenosis has not been well described. We sought to evaluate the correlates of pre- and post-PTCA coronary blood flow to shed light on potential modifiable determinants.The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 hours of occurrence of either unstable angina pectoris or acute MI. Coronary blood flow was assessed with the corrected TIMI frame count (CTFC), and clinical outcomes were assessed at 30 days.In addition to tighter and longer minimum lumen diameters (MLDs), the multivariate correlates of slower flow before PTCA also included the presence of thrombus, collaterals, left coronary artery lesion location, acute MI, and8F catheter size. As well as the above variables, type C and D dissection grades were related to slower post-PTCA CTFC. Death, or the composite of death/MI/coronary artery bypass graft at 30 days, was more frequent among patients with slower post-PTCA CTFCs and those with post-PTCA thrombus. In a multivariate model correcting for reference segment diameter and MLD, the post-PTCA CTFC was an independent predictor of late lumen loss and the follow-up MLD at 6 months. As a single index that integrates functional and anatomical aspects of the post-PTCA results, the ratio of CTFC/MLD was associated with death/MI by 30 days.In addition to MLD, variables such as the presence of thrombus, left coronary artery lesion location, and dissection grade also are associated with slower coronary blood flow after PTCA. In turn, post-PTCA CTFCs were an independent predictor of late lumen loss and follow-up MLDs. Furthermore, patients who die or who sustain other adverse cardiac events have slower coronary blood flow and greater thrombus burden after PTCA.

Background Clarification of the specific clinical course of non-ST-segment elevation acute coronary syndromes (NSTEMI ACS), including recurrent ischemic events and need for coronary revascularization, is important given the increasing economic pressure to shorten the length of hospitalization and therefore the duration of acute therapy. To examine the mode and timing of subsequent cardiac events, we analyzed pooled data from the ESSENCE and TIMI 11B studies of antithrombotic therapy in NSTEMI ACS. Methods The daily event rates (with confidence intervals) during the first 43 days and the monthly average event rates during the first year were tabulated for 7081 patients. Results The median antithrombotic treatment duration was 3.2 days, whereas the highest absolute frequency of recurrent angina prompting urgent revascularization, myocardial infarction, or death after hospital admission occurred on day 2, day 3, and day 8, respectively. Coronary revascularization was performed in 32% of patients, with the greatest number occurring on day 4. Only 12% of the end point events were adjudicated as being periprocedural. The median length of hospital stay was 7 days. Conclusions Despite aggressive antithrombotic therapy, a significant proportion of patients with NSTEMI ACS have recurrent ischemia precipitating urgent revascularization or infarction within the first few days, whereas the highest risk of death occurs later, after the first week. (Am Heart J 2002;143:63-9.)

Objective We sought to identify, by use of serum cardiac markers, patients at low risk for 30-day mortality after STsegment elevation myocardial infarction. Background Baseline cardiac markers are currently used to identify patients at increased risk for short-term events. We hypothesized that serum markers measured after treatment could identify patients at low risk for 30-day mortality. Methods A total of 839 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B study had myoglobin, cardiac-specific troponin-I, creatine kinase (CK)-MB measurements at the following time points; baseline, 90 minutes, and 3 and 12 hours after thrombolysis. By use of receiver operating characteristic analysis, thresholds were derived to predict 30-day mortality with at least 95% negative predictive value. Results Ninety minutes after thrombolysis myoglobin was superior to troponin-I or CK-MB in identifying patients at low risk for mortality. The 30-day mortality for 12-hour myoglobin ≤239 ng/mL was 1.4% compared with 9.1% for levels >239 ng/mL (P

Background Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. Methods ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. Results Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution ( P =.008). Conclusions A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy. (Am Heart J 2001;141:592-8.)

Identification of individuals in the community with left ventricular systolic dysfunction (LVSD) or left ventricular hypertrophy (LVH) may allow earlier initiation of disease-modifying treatment. We performed a comprehensive evaluation of the screening performance of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) for LVSD or LVH.In 2,429 subjects without a history of heart failure, myocardial infarction, valvular abnormalities, or a serum creatinine2.0 mg/dL enrolled in the Dallas Heart Study, measurement of BNP and NT-proBNP and cardiovascular magnetic resonance imaging were performed.B-type natriuretic peptide and NT-proBNP were robustly associated with magnetic resonance imaging-defined LVH and LVSD (ejection fraction55%) among men and women (P.0001 for each). In the overall population, neither test discriminated well for LVH or LVSD (area under the receiver operating characteristic curve [AUROC]0.7). Among women, no differences in AUROC were observed between BNP and NT-proBNP. Among men, AUROCs were similar between BNP and NT-proBNP in the overall population, but among subgroups age 50 or older, or with hypertension, the AUROCs for NT-proBNP (0.73-0.79) were higher than for BNP (0.63-0.69, P.05 for each comparison). Compared with subjects with isolated BNP elevation (97.5th percentile), those with isolated NT-proBNP elevation had worse renal function and more LVH and coronary calcium (P.05 for each).Overall, neither BNP nor NT-proBNP accurately discriminated subjects with LVH or LVSD in this predominately young and healthy population-based cohort. However, among high-risk men, NT-proBNP performed slightly better than BNP and comparably with other routinely used screening tests such as prostate-specific antigen measurement for prostate cancer.

Background It has recently been shown that statins increase the myocardial content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of PG production may protect the gastric mucosa and prevent gastrointestinal (GI) bleeding. We hypothesized that statins would lower the risk of GI bleeding associated with antiplatelet therapy in patients with acute coronary syndromes (ACS). Methods We retrospectively analyzed data on 10 288 patients with ACS included in the OPUS-TIMI 16 trial and received aspirin and either the oral IIb/IIIa inhibitor orbofiban or placebo. Results Inhospital GI bleeding rate was significantly lower in patients who were receiving lipid-lowering drugs before admission compared with those who were not (0.2% vs 0.6%, P = .031). Throughout 10 months of follow-up, GI bleeding occurred in 1.8% of non–statin users compared with 1.0% of statin users (P = .001). Statin use was associated with less overall bleeding in both the orbofiban (1.4% vs 2.4%, P = .006) and the placebo groups (0.2% vs 0.8%, P = .047). Severe and major bleeding occurred less frequently with statin use (0.8% vs 1.5%, P = .001) in both the orbofiban (1.1% vs 2.0%, P = .006) and the placebo groups (0.1% vs 0.5%, P = .119). Logistic regression analysis showed that age >65 years, orbofiban treatment, Killip class >1, history of cerebrovascular disease, and calcium-channel blocker use were associated with higher risk of GI bleeding, whereas statin therapy was associated with a lower risk (odds ratio 0.68, 95% CI 0.45-1.04, P = .079). Conclusions Statins may exert protective effect against GI bleeding in patients with ACS. Additional studies are warranted to explore this additional potential benefit of statins.