J. Frederick McNeer

Efficacy and safety of a potent new selective Cholesterol absorption inhibitor, Ezetimibe, in patients with primary hypercholesterolemia

The efficacy and safety of ezetimibe, a new cholesterol absorption inhibitor, was evaluated in this randomized, double-blind, placebo-controlled trial of 892 patients with primary hypercholesterolemia. After > or =2 weeks on the National Cholesterol Education Program (NCEP) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in, patients with low-density lipoprotein (LDL) cholesterol 130 to 250 mg/dl and triglycerides < or =350 mg/dl were randomized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks. The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point. A total of 434 men and 458 women (ages 18 to 85 years) received randomized treatment (666 ezetimibe 10 mg, 226 placebo). Demographics and baseline characteristics were similar between treatment groups. Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9%, compared with an increase of 0.4% with placebo (p <0.01). Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups, regardless of risk-factor status, gender, age, race, or baseline lipid profile. Ezetimibe effects on LDL cholesterol occurred early (2 weeks) and persisted throughout the 12-week treatment period. Compared with placebo, ezetimibe 10 mg also significantly improved calculated LDL cholesterol, apolipoprotein B, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and HDL(3) cholesterol (p <0.01). Ezetimibe was well tolerated. There were no differences in laboratory or clinical safety parameters, or gastrointestinal, liver, or muscle side effects from that of placebo. Ezetimibe 10 mg/day is well tolerated, reduces LDL cholesterol approximately 17%, and improves other key lipid parameters.

Prognostic value of ventricular arrhythmias associated with treadmill exercise testing in patients studied with cardiac catheterization for suspected ischemic heart disease

The prognostic information provided by ventricular arrhythmias associated with treadmill exercise testing was evaluated in 1,293 consecutive nonsurgically treated patients undergoing an exercise test within 6 weeks of cardiac catheterization. The 236 patients with simple ventricular arrhythmias (at least one premature ventricular complex, but without paired complexes or ventricular tachycardia) had a higher prevalence of significant coronary artery disease (57 versus 44%), three vessel disease (31 versus 17%) and abnormal left ventricular function (43 versus 24%) than did patients without ventricular arrhythmias. Patients with paired complexes or ventricular tachycardia had an even higher prevalence of significant coronary artery disease (75%), three vessel disease (39%) and abnormal left ventricular function (54%). In the 620 patients with significant coronary artery disease, patients with paired complexes or ventricular tachycardia had a lower 3 year survival rate (75%) than did patients with simple ventricular arrhythmias (83%) and patients with no ventricular arrhythmias (90%). Ventricular arrhythmias were found to add independent prognostic information to the noninvasive evaluation, including history, physical examination, chest roentgenogram, electrocardiogram and other exercise test variables (p = 0.03). Ventricular arrhythmias made no independent contribution once the cardiac catheterization data were known. In patients without significant coronary artery disease, no relation between ventricular arrhythmias and survival was found.

Hospital discharge one week after acute myocardial infarction.

Sixty-seven consecutive patients who had suffered an acute myocardial infarction but no serious complications during the first to fourth hospital days were considered for a trial of hospital discharge at one week. Thirty-three of the 67 patients were discharged at one week, the remainder having a mean hospital stay of 11 +/- 2 days. The incidence of late complications and recurrent infarctions, as well as mortality and functional status, were determined in all patients six months after discharge. No serious complications occurred in either subgroup within three weeks after discharge. There were no deaths in either subgroup and no difference in functional status at six months. Patients without serious complications during the four days after an acute myocardial infarction can be spared the economic costs and psychologic stress of prolonged hospitalization.

The nature of treatment selection in coronary artery disease. Experience with medical and surgical treatment of a chronic disease.

This report presents our experience with the medical and surgical management of patients with coronary heart disease and uses this experience to document the role of a computerized medical information system in the long-term management of patients with a chronic disease. Of 781 consecutively evaluated patients, 402 were treated medically and 379 were treated with aortocoronary bypass surgery. At two years post-zero time, more than twice as many surgical survivors were pain free, but the survival was the same in the medical (83%) and surgical (85%) cohorts. The medically and surgically treated patients were compared with respect to 89 baseline characteristics. The cohorts were remarkably similar. Correction for baseline inequalities did not affect the fact that two-year survival was the same in both cohorts. One subgroup was identified in which surgically treated patients had a higher two-year survival. Other subgroups were identified in which therapy did not appear to affect two-year survival.

Cardiac Arrest Complicating Acute Myocardial Infarction: Predictability and Prognosis

Eleven percent of 905 consecutive patients with acute myocardial infarction admitted to the coronary care unit at Duke University Medical Center experienced cardiac arrest. Subgroups of patients at high and low risk for cardiac arrest were identified. Cardiac arrest was experienced by 17 percent of patients with signs of heart failure on admission but by only 3 percent of patients without diabetes mellitus, prior myocardial infarction or heart failure by history or on admission. Only 59 percent of patients with cardiac arrest survived hospitalization compared with 88 percent of those without cardiac arrest. Long-term survival for the 765 hospital survivors was significantly greater in the group without than in the group with arrest at each yearly interval from 1 through 5 years; the 2 year survival rate was 50 and 77 percent, respectively, in these two groups. Many of the deaths among the hospital survivors occurred in patients with signs of heart failure during hospitalization. Among 668 hospital survivors who had mild or no heart failure during hospitalization, cardiac arrest continued to be a significant predictor of mortality. The mode of death among hospital survivors did not differ in the groups with and without cardiac arrest; for example, the incidence rate of sudden death in the two groups was 44 and 37 per cent, respectively. In light of recent reports suggesting that the prophylactic use of antiarrhythmic agents can virtually eliminate virtually fibrillation during the hospital phase of acute myocardial infarction, we contend that such use may substantially reduce both long-term and hospital mortality after acute myocardial infarction.

Complete and incomplete revascularization at aortocoronary bypass surgery: Experience with 392 consecutive patients

Abstract This report presents our experience with “complete” and “incomplete” revascularization in 392 consecutive patients undergoing aortocoronary artery bypass surgery. Patients were considered to have had “complete” revascularization only if all major coronary arteries with 70 per cent occlusion received at least one bypass graft. Patients were considered “incompletely” revascularized if any vessel with a 70 per cent or more occlusion did not receive at least one bypass graft. The “completely” revascularized cohort contained 186 patients and the “incompletely” revascularized cohort contained 206 patients. The survival of the “completely” and “incompletely” revascularized cohorts was compared postoperatively and at 6, 12, and 24 months using the Chi-square test. Relief of anginal pain rates were compared at 6, 12, and 24 months using the Chi-square test. Analyses were repeated after stratifying for number of vessels diseased. The subgroup with one vessel diseased was, by definition, “completely” revascularized. No significant difference in survival or relief of anginal pain was demonstrated in the total group or in subgroups with 2 and with 3 vessels diseased. The data indicate that “complete” revascularization is not closely coupled to two-year survival or relief of anginal pain.