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Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

A 50-year-old man arrives in the emergency room with signs and symptoms occurring intermittently over a period of 48 h consistent with a myocardial infarction. He has several major risk factors for a recurrent event. A number of management strategies have already been attempted. Two opinions for further management are presented.

Over a one year period (1979 to 1980) all cardiac admissions to the coronary care units (CCU) and all intensive care unit (ICU) overflow admissions in Hamilton, Ontario, a city of approximately 375,000 people, were documented. Mortality status was determined one year following admission. There were 2004 individuals with either acute myocardial infarction (810), unstable angina (811) or other chest pain (783) as their first CCU/ICU admitting diagnosis that year. Mortalities in-hospital and by one year were: acute myocardial infarction 17 and 27%, respectively; unstable angina 1.5 and 9.2%, respectively; and other chest pain 1.4 and 3.1%, respectively. Of one year mortality following acute myocardial infarction, 63% occurred during the initial hospitalization, whereas this figure was 16% for unstable angina. For acute myocardial infarction, female mortality was greater than male mortality overall and in all but one age category. Mortality following acute myocardial infarction and unstable angina was strongly related to age. Repeat CCU/ICU admission occurred in 24% of acute myocardial infarction, 28% of unstable angina and 15% of other chest pain, while a total of death or nonfatal CCU/ICU readmission occurred in 31% of acute myocardial infarction, 32% of unstable angina and 17% of other chest pain.

All cardiac admissions to coronary care unit (CCU) beds and all intensive care unit (ICU) overflow admissions in Hamilton, Ontario, a city of 375,000 people, were documented over a one-year period, 1979-80. There were 4180 such admissions, 89% of them to CCUs. In the CCUs, 22% of patients had acute myocardial infarction, 24% unstable angina and 21% other chest pain. For myocardial infarction, hospitalization rate was 224 per 100,000, hospital mortality 42 per 100,000 and 48% of all myocardial infarction deaths in the community occurred in hospital. Of all myocardial infarction patients admitted to the CCU, 69% were correctly diagnosed on admission (sensitivity) and of all the admission diagnoses of myocardial infarction, 72% were eventually found to be correct (positive predictive value). Mean values for CCU patients overall were age 62.5 years, CCU stay 2.88 days and hospital stay 9.7 days; and for acute myocardial infarction patients in CCUs, age 63.4 years, CCU stay 3.98 days and hospital stay 13.28 days. For myocardial infarction, CCU mortality was 10.9%, hospital mortality 15.2% and, with the inclusion of ICU overflow patients, hospital mortality was 17.6%. Age-specific mortality for myocardial infarction was 9.7% age 45 to 64 years, and 32.8% over 70 years.