In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Patients with heart failure have increased vascular resistance and evidence for increased neurohumoral drive. High levels of circulating norepinephrine are found in patients with heart failure, but it is not known whether they reflect increased sympathetic neural activity or result from altered synthesis, release, or metabolism of norepinephrine. We used microneurography (peroneal nerve) to directly record sympathetic nerve activity to muscle (mSNA) and also measured plasma norepinephrine levels in patients with heart failure and in normal control subjects. Our goal was to determine whether sympathetic nerve activity is increased in patients with heart failure and whether plasma norepinephrine levels correlate with levels of mSNA in heart failure. Resting muscle sympathetic nerve activity in 16 patients with moderate to severe heart failure (54 + 5 bursts/min, mean + SE) was significantly higher (p < .01) than the levels of activity in either nine age-matched normal control subjects (25 ± 4 bursts/min) or 19 "young" normal control subjects (24 + 2 bursts/min). We found a significant correlation between plasma norepinephrine levels and mSNA (r = .73, p < .05). Neither mSNA nor plasma norepinephrine levels correlated with total systemic vascular resistance, cardiac index, left ventricular ejection fraction, or heart rate. However, both mSNA and plasma norepinephrine levels showed significant positive correlations (p < .05) with left ventricular filling pressures (r = .80, mSNA vs filling pressures; r = .82, norepinephrine levels vs filling pressures) and mean right atrial pressure. The results of the study provide the first direct evidence of increased central sympathetic nerve outflow in patients with heart failure and the first direct evidence that plasma norepinephrine levels show a reasonable correlation with sympathetic nerve activity to muscle in these patients. Furthermore, the data suggest that preload is an important determinant of SNA in these patients. Circulation 73, No. 5, 913-919, 1986. A HALLMARK of advanced heart failure is high peripheral vascular resistance.' Several neurohumoral factors may contribute to the increased vascular resistance, including increased activity of the renin-angiotensin system,24 elevated levels of arginine vasopressin,5 and increased activity of the sympathetic nervous

The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated.

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