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ObjectivesThis study sought to determine the association of pre-hospital electrocardiograms (ECGs) and the timing of reperfusion therapy for patients with ST-segment elevation myocardial infarction (STEMI).BackgroundPre-hospital ECGs have been recommended in the management of patients with chest pain transported by emergency medical services (EMS).MethodsWe evaluated patients with STEMI from the NCDR (National Cardiovascular Data Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were transported by EMS from January 1, 2007, through December 31, 2007. Patients were stratified by the use of pre-hospital ECGs, and timing of reperfusion therapy was compared between the 2 groups.ResultsA total of 7,098 of 12,097 patients (58.7%) utilized EMS, and 1,941 of these 7,098 EMS transport patients (27.4%) received a pre-hospital ECG. Among the EMS transport population, primary percutaneous coronary intervention was performed in 92.1% of patients with a pre-hospital ECG versus 86.3% with an in-hospital ECG, whereas fibrinolytic therapy was used in 4.6% versus 4.2% of patients. Median door-to-needle times for patients receiving fibrinolytic therapy (19 min vs. 29 min, p = 0.003) and median door-to-balloon times for patients undergoing primary percutaneous coronary intervention (61 min vs. 75 min, p < 0.0001) were significantly shorter for patients with a pre-hospital ECG. A suggestive trend for a lower risk of in-hospital mortality was observed with pre-hospital ECG use (adjusted odds ratio: 0.80, 95% confidence interval: 0.63 to 1.01).ConclusionsOnly one-quarter of these patients transported by EMS receive a pre-hospital ECG. The use of a pre-hospital ECG was associated with a greater use of reperfusion therapy, faster reperfusion times, and a suggested trend for a lower risk of mortality.

ObjectivesThe goal of this study was to determine whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38) study.BackgroundOptimal aspirin dosing after acute coronary syndromes remains uncertain. Previous studies have raised questions regarding an interaction between high-dose aspirin and the potent antiplatelet agent ticagrelor.MethodsIn TRITON–TIMI 38, we classified 12,674 patients into low-dose (

ObjectivesThis study sought to determine whether the novel biomarker monocyte chemoattractant protein (MCP)-1 adds prognostic value to standard risk assessment tools and biomarkers after acute coronary syndromes (ACS).BackgroundMonocyte chemoattractant protein-1 is a chemokine recruiting signal for monocytes that may function as both a mediator and biomarker of ACS.MethodsMonocyte chemoattractant protein-1 was measured at baseline (n = 4,244), 4 months (n = 3,603), and 12 months (n = 2,950), and correlated with clinical events in the Z phase of the A to Z (Aggrastat to Zocor) trial, which compared early intensive versus delayed and less intensive statin therapy after ACS.ResultsRates of death and the composite end points of death or myocardial infarction (MI); death, MI, or heart failure; and cardiovascular death, MI, readmission for ACS, or stroke increased across baseline quartiles of MCP-1 and among patients with MCP-1 greater than versus less than or equal to the pre-specified threshold of 238 pg/ml (p < 0.01 for each). After adjustment for standard risk predictors and levels of C-reactive protein and B-type natriuretic peptide, MCP-1 >238 pg/ml remained independently associated with mortality (hazard ratio 2.16; 95% confidence interval 1.54 to 3.02) and with each composite end point, and increased the C-statistic of the fully adjusted mortality model from 0.76 to 0.78 (p < 0.0001). A value of MCP-1 >238 pg/ml at the 4-month follow-up visit was also independently associated with mortality after 4 months (hazard ratio 1.76; 95% confidence interval 1.12 to 2.76). Elevated MCP-1 levels did not identify patients who derived incremental benefit from intensive statin therapy.ConclusionsMonocyte chemoattractant protein-1 provides independent prognostic value in the acute and chronic phases after ACS and merits further evaluation as a prognostic marker and potential therapeutic target.

ObjectivesThe 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).BackgroundThe 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.MethodsThe 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.ResultsThere 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.ConclusionsThere 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.

BackgroundVorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease.ObjectivesThe goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting.MethodsTRA 2°P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria.ResultsA total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTO moderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p < 0.001).ConclusionsThe rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2°P-TIMI 50] [P04737]; NCT00526474)

ObjectivesThis study was designed to determine the relationship between clopidogrel and early ST-segment resolution (STRes) and the interaction of the two with clinical outcomes after fibrinolysis.BackgroundST-segment resolution is an early noninvasive marker of coronary reperfusion.MethodsThe CLARITY–TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis in Myocardial Infarction 28) trial randomized 3,491 patients with ST-segment elevation myocardial infarction (STEMI) undergoing fibrinolysis to clopidogrel versus placebo. ST-segment resolution was defined as complete (>70%), partial (30% to 70%), or none (

ObjectivesWe evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON–TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel–Thrombolysis In Myocardial Infarction) analysis.BackgroundPrasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding.MethodsLandmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial.ResultsSignificant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non–coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial.ConclusionsBoth the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y12 receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591)

ObjectivesThis study sought to evaluate the safety and efficacy of achieving very low calculated low-density lipoprotein (LDL) levels with intensive statin therapy.BackgroundIntensive statin therapy reduces clinical events occurring after acute coronary syndrome (ACS) and may result in LDL levels markedly lower than guideline levels. Prior epidemiologic and preclinical studies raise concerns about the safety of very low cholesterol levels.MethodsThe Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study compared intensive therapy (atorvastatin, 80 mg) and moderate therapy (pravastatin, 40 mg) in patients after ACS. Patients treated with atorvastatin were divided by four-month LDL values into groups: >100, >80 to 100 (reference-range-meeting guidelines), >60 to 80, >40 to 60, and 80 to 100 mg/dl (14%), >60 to 80 mg/dl (31%), >40 to 60 mg/dl (34%), and

ObjectivesWe sought to evaluate a simple risk index based on age and vital signs in a community sample of patients with ST-segment elevation myocardial infarction (STEMI).BackgroundA simple risk index based on age and vital signs (heart rate × [age/10]2/systolic blood pressure) developed from patients with STEMI accurately predicts mortality in clinical trials of fibrinolysis. The application of such a tool in an unselected population is necessary to evaluate its utility in clinical practice.MethodsTo evaluate the Thrombolysis In Myocardial Infarction (TIMI) risk index for routine practice, we tested it in the National Registry of Myocardial Infarction (NRMI)-3 and -4. The risk index was evaluated as a continuous variable in patients with STEMI from NRMI and in subgroups based on age and reperfusion status.ResultsA total of 153,486 patients with STEMI were eligible. As anticipated, STEMI patients in NRMI had a higher risk index profile, as compared with those in the clinical trial (median 26.9 vs. 20, p < 0.0001). Classification of NRMI patients with STEMI into risk groups revealed a significant graded relationship with mortality (0.9% to53.2%, ptrend< 0.0001, cstatistic 0.79). The discriminatory capacity of the risk index was particularly strong in the 81,679 patients receiving reperfusion therapy (0.6% to60%, ptrend< 0.0001, cstatistic 0.81). For the 71,807 patients not receiving reperfusion therapy, a strong graded relationship remained (1.9% to 52.2%, ptrend< 0.0001, cstatistic 0.71). Among the elderly, although the distribution of scores was shifted toward higher risk, the performance remained (0% to 53.1%, ptrend< 0.0001, cstatistic 0.71).ConclusionsA simple risk index from baseline clinical variables routinely obtained at the first patient encounter predicted mortality in a large unselected heterogeneous group of patients with STEMI.