Long-term ENDUR-ACIN® treatment is a safe, effective treatment for dyslipidemia, study shows

Summary

This clinical trial was designed to assess the safety of long-term use of ENDUR-ACIN® wax matrix niacin and its potential synergy with oat bran for improving blood lipid levels.

For this study, researchers enrolled subjects who completed a shorter clinical trial (Keenan JM, et al. Arch Intern Med. 1991;151(7):1424-32) investigating ENDUR-ACIN® treatment (up to 1,000-2,000 mg/day for 20 weeks) for dyslipidemia. Of the 158 subjects who completed the shorter trial, 98 (62%) agreed to participate in this sequel study. A 4-month interval existed between the studies, effectively creating a 4-month washout period.

Subjects with elevated LDL cholesterol levels with low- to moderate-risk for heart disease were originally recruited from community cholesterol screenings and chart reviews from family practice clinics. No selection bias was found between the group of subjects in the original and this sequel study. The only significantly (P<.05) different variable was age (mean age 52 years in sequel study vs. 46 years in original study).

The study design was sequential with all subjects first consuming oat bran alone (28 g, twice daily, instant hot oat bran cereal for 6 weeks) (Phase 1). Next, they took ENDUR-ACIN® (1,500 mg/day for 6 weeks) in combination with the oat bran cereal (Phase 2). Finally, they took ENDUR-ACIN® alone (1,500 mg/day for the remaining 32 weeks (Phase 3). Subjects followed the American Heat Association’s Step 1 Diet during all phases of the study. Lipid profiles were obtained at baseline and at the end of each phase.

A total of 79% (77/98) of subjects completed the study with most (90%; 69/77) taking the full dosage of ENUR-ACIN® either as 750 mg, twice daily, or 500 mg, three times daily. Eight subjects reduced dosage to an average of 906 mg/day. Dropouts were 8% (8/98) due to intolerable side effects (e.g., flushing, digestive upset or headaches), 4% (4/98) due to elevated blood chemistries, and 9% (9/98) for personal reasons.

Based on pill count, compliance with ENDUR-ACIN® treatment was 93%. In subjects taking the full ENDUR-ACIN® dosage, no significant changes in blood lipids were found after the initial 6-week oat bran only phase (Phase 1). Adding ENDUR-ACIN® for another 6 weeks (Phase 2) significantly reduced total cholesterol (-10%) and LDL cholesterol (-14%) levels and the total-to-HDL cholesterol ratio (-8%) compared to baseline. These reductions were maintained through the 32-week Phase 3 period. No significant changes in HDL cholesterol or triglyceride levels were found throughout the study. A small number of subjects (n=7) experienced greater LDL reduction during Phase 2 than Phase 3 (-27% vs. -11%, respectively), suggesting a possible synergistic effect between oat bran and ENDUR-ACIN®.

In subjects taking the full ENDUR-ACIN® dosage, no significant changes in uric acid or bilirubin were reported. Serum glucose increased significantly (P<.05) from baseline to Phase 2, but self-resolved during Phase 3. Asymptomatic elevations in liver enzymes occurred over the course of the study, which returned to normal within 3 weeks or less after lowering the dosage or discontinuing treatment. An abnormal elevation of aspartate aminotransferase (AST) was reported in 3 subjects.

These findings indicate that long-term use of ENDUR-ACIN® is effective for the treatment of dyslipidemia with good patient compliance. Long term monitoring of blood chemistries, especially AST would be prudent, even when dosing is stable.