Phillip D. Toth

Long-Term Safety and Efficacy of a Once- Daily Niacin/Lovastatin Formulation for Patients With Dyslipidemia*

Combination therapy is increasingly recommended for patients with multiple lipid disorders, especially those at high risk for coronary events. We investigated the long-term safety and effectiveness of a new drug formulation containing once-daily extended-release niacin and lovastatin. A total of 814 men and women (mean age 59 years) with dyslipidemia were enrolled in a 52-week multicenter, open-label study. We used 4 escalating doses (niacin/lovastatin in milligrams): 500/10 for the first month, 1,000/20 for the second, 1,500/30 for the third, and 2,000/40 for the fourth month through week 52. Dose-dependent effects were observed for all major lipid parameters. At week 16, mean low-density lipoprotein (LDL) cholesterol and triglycerides were reduced by 47% and 41%, respectively; mean high-density lipoprotein (HDL) cholesterol was increased by 30% (all p <0.001). LDL/HDL cholesterol and total/HDL cholesterol ratios were also decreased by 58% and 48%, respectively. These effects persisted through week 52, except for the mean increase in HDL cholesterol, which had increased to 41% at 1 year. Lipoprotein (a) and C-reactive protein also decreased in a dose-related manner (by 25% and 24%, respectively, on 2,000/40 mg; p <0.01 vs baseline). Treatment was generally well tolerated. The most common adverse event was flushing, which caused 10% of patients to withdraw. Other adverse events included gastrointestinal upset, pruritus, rash, and headache. Drug-induced myopathy did not occur in any patient. The incidence of elevated liver enzymes to >3 times the upper limit of normal was 0.5%. Once-daily niacin/lovastatin exhibits substantial effects on multiple lipid risk factors and represents a significant new treatment option in the management of dyslipidemia.

Comparison of the effects of pindolol and atenolol on hemodynamic function in systemic hypertension

A randomized double-blind study was performed on a group of mild hypertensive patients (WHO class I) to compare the hemodynamic effects of pindolol and atenolol. Blood pressure (BP) was monitored with a mercury gauge sphygmomanometer, while cardiac function and peripheral arterial flows were measured by the noninvasive technique of bioelectric impedance. After a 2-week washout period, patients with a diastolic BP greater than 95 mm Hg but less than 114 mm Hg were randomized into the pindolol (29 patients) or atenolol (28) treatment groups. Patients were treated with 1 of the 2 drugs in an incremental fashion for 12 weeks. Cardiovascular function was measured after the washout period and at the end of the 12-week treatment period. Baseline hemodynamics were similar in both groups. The 2 drugs were equally effective in lowering both systolic and diastolic BP. Hemodynamically, pindolol lowered BP by decreasing total peripheral resistance (-406 +/- 145 dynes.s.cm-5) while atenolol decreased cardiac index (-0.2 +/- 0.1 liters/min/m2) associated with a decrease in heart rate (-12 +/- 2 beats/min). Regarding peripheral vascular beds, pindolol lowered arm vascular resistance (-198 +/- 72 mm Hg/liter/min) and leg vascular resistance (-73 +/- 25 mm Hg/liter/min), especially when subjects who did not respond to pindolol were excluded from the analysis. Both arm (5.5 +/- 5.4% increase above baseline) and leg (1.2 +/- 4.4% increase above baseline) arterial flow indexes were maintained with pindolol. Conversely, atenolol decreased the arm arterial flow index (-9,8 +/- 5.6% decrease below baseline), but not significantly and with no change in resistance (+54 +/- 62 mm Hg/liter/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of noninvasive bioelectric impedance to predict cardiac output in open heart recovery

Cardiac outputs (CO) measured by bioelectric impedance (Z) and thermodilution (TD) were compared in ten stable, non-ventilated male coronary artery bypass patients (mean age 59 +/- 12 years) in an open heart recovery unit. The measurements were obtained blindly in three sequential body positions (supine, 45 degrees, final supine) using either a calculated value for resistivity (p) (based upon hematocrit with blood sampled at the time of the study) to estimate CO(Z), or assumed values of p = 135.5 omega cm and p = 150 omega cm. The results indicate high correlations between the two measurement methods (range: r = 0.97 to 0.99) in the initial supine position for all resistivity conditions followed by a progressive decline when body position was changed to 45 degrees and supine (range: r = 0.74 to 0.90). The highest overall correlations and closest absolute mean cardiac output values were obtained when p was calculated from actual hematocrit values obtained at the time of the study. Applying a two-way ANOVA to assess the simultaneous effects of method (TD vx. Z) and position change (supine, 45 degrees, supine), no significant main effects or interactions were found when cardiac output values were estimated using the calculated measurement of p. However, significant main effects of method were found when p was assumed to be either 135.5 omega cm (p > or = 0.005) or 150.0 omega cm (p > or = 0.0001), with impedance showing a tendency to overestimate cardiac output. In conclusion, our findings suggest that impedance is a valid method to estimate cardiac output in this subpopulation of patients in open heart recovery provided that p is calculated at the time the study is performed.