Increased platelet reactivity in patients given orbofiban after an acute coronary syndrome: an OPUS-TIMI 16 substudy. Orbofiban in Patients with Unstable coronary syndromes. Thrombolysis In Myocardial Infarction

Patients receiving the oral glycoprotein IIb-IIIa inhibitor orbofiban in the OPUS -TIMI 16 trial had a paradoxical increase in platelet reactivity with respect to both fibrinogen binding and alpha-granule degranulation, suggesting a mechanism for the lack of efficacy of orbofiban in the trial. Thus, sensitive assays of platelet reactivity may be helpful in the design of further clinical studies and implementation of antiplatelet therapy in patients.     

Modified Thrombolysis in Myocardial Infarction (TIMI) risk score to risk stratify patients in the emergency department with possible acute coronary syndrome

Objective To assess the prognostic utility of the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients in the emergency department (ED) evaluated for possible acute coronary syndrome (ACS). Background The ability of the TIMI risk score to risk stratify patients at initial presentation in the ED with chest pain of unclear etiology is uncertain. Methods We investigated the prognostic utility of the TIMI risk score in 947 consecutive patients evaluated in the ED for possible ACS. A multivariate analysis was done to evaluate the independent predictive power of the individual components of the TIMI risk score to predict an adverse event at 30 days (all-cause death, myocardial infarction, and coronary revascularization). Results There were 151 (16%) patients diagnosed with ACS. At 30 days there were 48 (5%) deaths, 84 (9%) myocardial infarctions, and 49 (5%) coronary revascularization procedures. The mean TIMI risk score was significantly higher in patients with an adverse event compared with those without (2.6 ± 1.3 vs. 1.7 ± 1.2, P < 0.0001). Four of the 7 TIMI risk factors (age ≥65 years, ST segment deviation ≥0.5 mm elevated troponin I, and coronary stenosis ≥50%) were independently associated with adverse events. A simplified TIMI risk score was computed and was found to have similar prognostic ability as the 7 variable TIMI risk score. Conclusion A modified TIMI risk score may simplify risk stratification of ED patients with undifferentiated chest pain.     

One-year outcome after therapy with tissue plasminogen activator: report from the Thrombolysis and Angioplasty in Myocardial Infarction trial

To evaluate the long-term effects of reperfusion with tissue plasminogen activator (t-PA) and an aggressive strategy of revascularization with angioplasty and coronary artery bypass grafting, we obtained 1-year follow-up results from 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI I) trial. All patients were treated with 100 to 150 mg of t-PA intravenously over 6 to 8 hours, and coronary angiography was performed within 90 minutes of initiation of therapy. In 197 patients with suitable anatomic characteristics, angioplasty was either performed immediately or was deferred for 7 to 10 days on a randomized basis. The remainder of the patients were treated as considered clinically appropriate. The in-hospital mortality rate was 7%, and only 1.9% of patients died in the first year after discharge from the hospital; three patients died of cardiac events and four died of noncardiac causes. Ninety-four percent of patients discharged alive from the hospital remained alive and had no myocardial infarctions during the first 12 posthospital months. Revascularization procedures after discharge from the hospital included angioplasty in 8% of patients and coronary artery bypass grafting in 5%. The high survival rates were evident in high-risk groups defined by age, ejection fraction, and extent of coronary artery disease. At 1-year follow-up 64% of patients less than 65 years of age were employed and only 10% reported that they were disabled; 94% of patients were in Canadian Heart Association class I or II. These low rates of follow-up events suggest a change in the "natural history" of the first year after acute myocardial infarction.     

Platelet function in clopidogrel-treated patients with acute coronary syndrome.

Percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) is associated with increased risk of thrombotic complications. ACS enhances platelet activation; whether pretreatment with clopidogrel is sufficient to suppress platelet function in patients with ACS is not known. This study assessed platelet function in patients with and without ACS prior to PCI and after pretreatment with a single dose of 600 mg clopidogrel. Blood samples of 402 patients prior to PCI with (n = 119) or without (n = 283) ACS were collected at least 2 h after 600 mg clopidogrel administration. Maximal platelet aggregation in response to ADP (5 and 20 micromol/l), collagen (4 microg/ml) and TRAP (25 micromol/l) was measured with optical aggregometry. Surface expression of glycoprotein IIb/IIIa and P-selectin was assessed with flow cytometry at baseline and after stimulation with 5 and 20 micromol/l ADP. Agonist-induced platelet aggregation did not differ significantly between patients with and without ACS (P > or = 0.15). Parameters of platelet activation (glycoprotein IIb/IIIa and P-selectin surface expression) were significantly higher in ACS patients at baseline and after 5 and 20 micromol/l ADP stimulation (P < 0.0001). Patients with ACS continue to exhibit increased platelet activation after pretreatment with 600 mg clopidogrel. This finding supports the need for additional platelet function inhibition during PCI in patients with ACS.     

Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.     

Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction.

OBJECTIVES: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.     

Suboptimal medical care of patients with STElevation Myocardial Infarction and Renal Insufficiency: results from the Korea acute Myocardial Infarction Registry

ABSTRACT: BACKGROUND: The clinical outcomes of ST-segment elevation myocardial infarction (STEMI) are poor in patients with renal insufficiency. This study investigated changes in the likelihood that patients received optimal medical care throughout the entire process of myocardial infarction management, on the basis of their glomerular filtration rate (GFR). METHODS: This study analyzed 7,679 patients (age, 63 +/- 13 years; men 73.6 %) who had STEMI and were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to August 2008. The study subjects were divided into 5 groups corresponding to strata used to define chronic kidney disease stages. RESULTS: Patients with lower GFR were less likely to present with typical chest pain. The average symptom-to-door time, door-to-balloon time, and symptom-to-balloon time were longer with lower GFR than higher GFR. Primary reperfusion therapy was performed less frequently and the results of reperfusion therapy were poorer in patients with renal insufficiency; these patients were less likely to receive adjunctive medical treatment, such as treatment with aspirin, clopidogrel, beta-blocker, angiotensin-converting enzyme (ACE) inhibitor/angiotensinreceptor blocker (ARB), or statin, during hospitalization and at discharge. Patients who received less intense medical therapy had worse clinical outcomes than those who received more intense medical therapy. CONCLUSIONS: Patients with STEMI and renal insufficiency had less chance of receiving optimal medical care throughout the entire process of MI management, which may contribute to worse outcomes in these patients.     

Quantitative radionuclide assessment of regional ventricular function after thrombolytic therapy for acute myocardial infarction: results of phase I Thrombolysis in Myocardial Infarction (TIMI) trial

In Thrombolysis in Myocardial Infarction (TIMI) Phase I,290 patients with acute myocardial infarction were randomized to either intravenous recombinant tissue-type plasminogen activator (rt-PA) or intravenous streptokinase. Two hundred twenty-nine patients had radionuclide ventriculograms at discharge for assessment of global and regional left ventricular ejection fraction. Among these 229 patients 185 had totally occluded infarct-related arteries, and angiographic reperfusion of the infarct-related artery occurred in 69% of patients treated with rt-PA and 28% of patients treated with streptokinase (p less than 0.001). Mean global left ventricular ejection fraction was not different for rt-PA-treated patients compared with streptokinase-treated patients (0.46 versus 0.45). However, the average regional ejection fraction of the regions subtended by the infarct-related artery showed a trend toward better average infarct region ejection fraction in patients treated with rt-PA than in patients treated with streptokinase (0.40 versus 0.36; 0.05 less than p less than 0.06). Analysis of data according to perfusion status of the infarct-related artery showed no difference in mean global left ventricular ejection fraction between patients with sustained versus nonsustained reperfusion (0.47 versus 0.44). However, there was better average regional ejection fraction of the region subtended by the infarct-related artery in patients with sustained reperfusion (0.40 versus 0.36; p less than 0.01). Thus, quantitation of regional left ventricular function by radionuclide techniques provides a noninvasive means for evaluating the effects of thrombolysis. This study suggests a direct relation between improvement of regional left ventricular function and the greater infarct-related artery patency rate achieved by rt-PA compared with streptokinase.     

Impact of injections during diagnostic coronary arteriography on coronary patency in the setting of acute myocardial infarction from the TIMI trials. Thrombolysis In Myocardial Infarction

The mechanical force of injection at 90 minutes opens 13.4% of occluded arteries, but overall, only 2.4% of all culprit arteries (already open and occluded combined) are opened. Thus, although some arteries are opened by the force of hand injection, the frequency of mechanical opening among all arteries is low, and hand injections appear to alter current 80% patency rates by approximately 2.5%.     

Impaired coronary blood flow in patients with metabolic syndrome: documented by Thrombolysis in Myocardial Infarction (TIMI) frame count method

Background

Endothelium plays an important role in regulating coronary vascular tone. In addition, several of cardiovascular risk factors that are associated metabolic syndrome have been reported to be associated with endothelial dysfunction. In the present study we aimed to evaluate the coronary blood flow in patients with metabolic syndrome by means of the Thrombolysis in Myocardial Infarction (TIMI) frame count.

Method

Forty-two patients with metabolic syndrome (group I) and 42 control subjects without metabolic syndrome (group II) were included in the study. All subjects had angiographically proven normal coronary arteries. Diagnosis of metabolic syndrome was based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines published in 2001. Coronary flow rates of all subjects were documented by TIMI frame count method.

Results

TIMI frame counts for each of the major epicardial coronary arteries were found to be significantly higher in patients with metabolic syndrome compared with control subjects (corrected TIMI frame count for left anterior descending coronary artery: 35 ± 7 vs 25 ± 7, respectively; left circumflex coronary artery: 32 ± 9 vs 25 ± 7, respectively; right coronary artery: 31 ± 9 vs 24 ± 5, respectively; P < .001 for all). Statistically significant independent relationships were found between TIMI frame count and body mass index (R² = 0.480, P = .009), waist circumference (R² = 0.551, P = .001), and triglyceride level (R² = 0.434, P = .036).

Conclusion

We have shown for the first time that patients with metabolic syndrome and angiographically normal coronary arteries have higher TIMI frame counts for all 3 coronary vessels, indicating impaired coronary blood flow, compared to control subjects without metabolic syndrome.     

Improving care for patients with acute coronary syndromes: initial results from the National Audit of Myocardial Infarction Project (MINAP)

Objective: To describe the improvements in care that have followed the introduction of an electronic data entry and analysis system providing contemporary feedback on the management of acute coronary syndromes in 230 hospitals in England and Wales.     

Myoglobin levels at 12 hours identify patients at low risk for 30-day mortality after thrombolysis in acute myocardial infarction: a Thrombolysis in Myocardial Infarction 10B substudy.

OBJECTIVE: We sought to identify, by use of serum cardiac markers, patients at low risk for 30-day mortality after ST-segment 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 < or = 239 ng/mL was 1.4% compared with 9.1% for levels > 239 ng/mL (P < .001). For 12-hour troponin-I (threshold 81.5 ng/mL), mortality was 1.9% versus 6.6% (P = .001) if above threshold; similarly for CK-MB at 12 hours (threshold 191 ng/mL) it was 3.3% versus 7.9% (P = .02). Multivariate analysis of baseline and posttreatment cardiac markers, age, sex, infarct artery location, and 90-minute TIMI flow grade identified only 12-hour myoglobin among the cardiac markers as independently predicting a low 30-day mortality (odds ratio 0.11, 95% confidence interval 0.02-0.50, P < .004). CONCLUSION: Serum cardiac markers can identify greater than two thirds of patients at low risk for 30-day mortality. 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.     

One-year results of the Thrombolysis in Myocardial Infarction investigation (TIMI) Phase II Trial.

BACKGROUND. The Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial randomized 3,339 patients to either an invasive (INV, n = 1,681) or a conservative (CON, n = 1,658) strategy after intravenous recombinant tissue-type plasminogen activator (rt-PA) for acute myocardial infarction. METHODS AND RESULTS. The patients assigned to the INV strategy routinely underwent cardiac catheterization, and when anatomically appropriate, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting 18-48 hours after infarction. CON patients had these procedures only in response to the occurrence of spontaneous or provoked ischemia. One-year follow-up data are available in 3,316 patients (99.3%). The primary trial end point, death and nonfatal reinfarction, occurred in 14.7% of INV patients and in 15.2% of CON patients (p = NS). When analyzed individually, there was no difference (p = NS) in death (INV, 6.9%; CON, 7.4%) or recurrent infarction (INV, 9.4%; CON, 9.8%) between the two groups. Anginal status at 1 year was also similar. Cardiac catheterization and PTCA were performed more often in INV (98.0% and 61.2%, respectively) compared with CON (45.2% and 20.5%, respectively) patients. At 1 year, the cumulative number of patients who underwent coronary bypass surgery (INV, 17.5%; CON, 17.3%) was similar in the two groups. CONCLUSIONS. The INV and CON strategies resulted in similar favorable outcomes at 1 year of follow-up. In particular, the rates of mortality and reinfarction were not different and were impressively low in both groups. One possible advantage of the INV strategy was detected in subgroup analyses. In patients with a history of myocardial infarction, the data are suggestive that 1-year mortality was lower in INV patients (10.3%) than in CON patients (17.0%) (p = 0.03).     

Early prognostic usefulness of C-reactive protein added to the Thrombolysis In Myocardial Infarction risk score in acute coronary syndromes

The aim of the present study was to evaluate whether an elevated plasma C-reactive protein (CRP) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with acute coronary syndromes. For this purpose, 1,846 consecutive patients with either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were included. The incidence of 30-day death and 14-day composite of death, myocardial infarction (or repeat myocardial infarction) and recurrent ischemia was the prespecified primary end point in the STEMI and NSTEACS cohorts, respectively. The incidence of the primary end point was 9.8% and 23.6% in the STEMI and NSTEACS cohorts, respectively. A significantly increased risk of the primary end point was present with an increase in the STEMI and NSTEACS TIMI risk score (p(trend) < 0.001 for the 2 groups). A plasma CRP value of > or = 5 and > or = 3 mg/L (defined by receiver-operating characteristic analysis) was associated with a significantly increased risk of the primary end point in the STEMI and NSTEACS cohorts, respectively (p < 0.001 for the 2 cohorts), and it was true throughout the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated plasma CRP level appears to be a marker that adds prognostic information to the validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score may be used together for enhanced risk stratification in the setting of acute coronary syndromes.     

Identification of acute myocardial infarction patients suitable for early hospital discharge after aggressive interventional therapy. Results from the Thrombolysis and Angioplasty in Acute Myocardial Infarction Registry

BACKGROUND. Very early (day 4) hospital discharge has recently been proposed for selected patients with acute myocardial infarction (MI). The purpose of this study was to determine the most useful factors for identifying acute MI patients treated with aggressive interventional therapy who could be safely discharged on day 4. METHODS AND RESULTS. We studied 708 patients enrolled in the Thrombolysis and Angioplasty in Acute Myocardial Infarction trials I-III. Patients dying in the first 3 days and those with early (days 1-3) emergency coronary artery bypass graft surgery (CABG), late elective CABG (greater than or equal to day 4), or urgent/emergency CABG resulting from a late elective coronary angioplasty were excluded. The remaining 580 patients were randomly divided into a training sample (group 1) that was used to build a logistic regression model for predicting the absence of a late major complication and a test sample (group 2) that was used to validate this model. For this study, patients were considered appropriate for day 4 hospital discharge if they did not experience any of the following for 30 days after MI: death, reinfarction, cardiogenic shock, pulmonary edema, sustained hypotension, sustained ventricular tachycardia, high-grade atrioventricular block, acute ventricular septal defect, and recurrent ischemia necessitating urgent CABG. In group 1, four variables were independent predictors of freedom from late major complications: absence of early sustained ventricular tachycardia or ventricular fibrillation, absence of early sustained hypotension or cardiogenic shock, fewer coronary arteries with significant (greater than or equal to 75%) stenosis, and a higher left ventricular ejection fraction. In group 2, 23% of patients had a logistic model prediction of a 3% or less chance of a late complication. These patients had no deaths or reinfarctions by day 30 and a 3% late major complication rate. CONCLUSIONS. The results of early cardiac catheterization and the absence of selected early (days 1-3) major complications do allow identification of a low risk subgroup of acute MI patients that may be suitable for very early discharge.     

Application of the Thrombolysis in Myocardial Infarction risk index in non-ST-segment elevation myocardial infarction: evaluation of patients in the National Registry of Myocardial Infarction.

OBJECTIVES: The purpose of this research was to evaluate the Thrombolysis In Myocardial Infarction risk index (TRI) to characterize the risk of death among patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: The TRI, calculated from baseline age, systolic pressure, and heart rate, was established in patients with ST-segment elevation myocardial infarction (STEMI) and is predictive of mortality. Patients presenting with NSTEMI are increasing compared to STEMI and constitute a group with varied risk. METHODS: The TRI was calculated in 337,192 patients from the National Registry of Myocardial Infarction with NSTEMI. Values and outcomes were compared with 153,486 patients with STEMI classified by reperfusion status. Comparisons of baseline characteristics and clinical outcomes stratified by TRI were made. RESULTS: There was a graded relationship between the TRI and mortality in patients with NSTEMI with a >30-fold difference in mortality rates between lowest and highest deciles (p < 0.0001). The index showed good discrimination (c = 0.73). Overall mortality in the group with NSTEMI was higher (10.9%) than patients with STEMI treated with (6.6%) but lower than for STEMI patients not receiving reperfusion therapy (18.7%). The higher risk in comparison to patients with STEMI treated with reperfusion therapy was explained largely by the higher-risk profile of the population with NSTEMI. CONCLUSIONS: There is a graded relationship between TRI and mortality in patients with NSTEMI. This simple risk index provides important information about mortality in patients across the spectrum of myocardial infarction, STEMI and NSTEMI. Early identification of NSTEMI patients who are at high risk of in-hospital mortality may provide clinicians with important information for initial triage and treatment.     

High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial.

AIMS: Patients with acute coronary syndrome (ACS) in the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study had diminished cardiovascular events after 16 weeks of treatment of atorvastatin 80 mg daily. We determined whether plasma lipoproteins at baseline and then at 6 weeks after randomization predicted clinical outcome. METHODS AND RESULTS: Cox proportional hazards models were constructed to determine relations between lipoproteins and clinical endpoint events. Baseline LDL cholesterol (LDL-C) did not predict outcome. In contrast, baseline HDL-C predicted outcome with a hazard ratio of 0.986 per mg/dL increment in HDL-C, P<0.001, indicating 1.4% reduction in risk for each 1 mg/dL increase in HDL-C. Atorvastatin treatment profoundly lowered LDL-C, but had minimal effect on HDL-C. Neither Week 6 LDL-C nor absolute change of LDL-C from baseline by Week 6 had any significant impact on clinical endpoints occurring between Week 6 and Week 16 after randomization. CONCLUSION: Plasma HDL-C, but not LDL-C, measured in the initial stage of ACS predicts the risk of recurrent cardiovascular events over the ensuing 16 weeks. LDL-C reduction does not account for the clinical risk reduction with atorvastatin treatment after ACS. This finding may suggest that the clinical benefit of atorvastatin after ACS is mediated by qualitative changes in the LDL particle and/or by non-lipid (pleiotropic) effects of the drug.