ENDUR-ACIN® shows significant benefits as part of a multi-drug therapy for blood lipid management, study shows
- Stepped-care, multi-drug therapy shows clinical benefits in patients with established CHD
- Therapeutic options include pravastatin, ENDUR-ACIN®, cholestyramine and gemfibrozil
- Combining ENDUR-ACIN® with pravastatin adds significant benefits for improving LDL and HDL cholesterol
- Therapy may be especially beneficial for aggressive management of blood lipids
This randomized, double-blind, placebo-controlled trial was designed to determine the efficacy and tolerability of a multi-drug therapy to improve low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in patients with documented coronary heart disease (CHD) and average lipid levels.
At total of 91 patients (80 men, 11 women) were enrolled into the study after discharge from two urban, tertiary care hospitals in Boston, Massachusetts. At baseline, patients had coronary heart disease, total cholesterol level below 250 mg/dl, total:HDL cholesterol ratio greater than 4.0, and a mean age of 58 years.
Patients were randomly assigned to receive a multi-drug, stepped-care, therapy (see below) or a placebo. Fasting blood lipid profiles and adverse effects were assessed every 6 weeks during drug titration and every 3 months thereafter. The average length of follow up was 125 weeks (range, 4 to 190 weeks). The trial ended after the mean duration of 2.5 years of treatment.
Stepped-Care Drug Therapy Algorithm*
- Step 1. Start therapy with pravastatin, 40 mg/day, given at night
- Step 2. If goal not reached after 6 weeks, add ENDUR-ACIN® wax matrix niacin, 750 mg, twice daily
- Step 3. If goal not reached after 6 weeks, increase ENDUR-ACIN® to 3 g/day over 3 weeks
- Step 4. If goal not reached after 6 weeks, add cholestyramine, titrated to 24 g/day or maximum daily dosage tolerated, in divided doses over 3 weeks
- Step 5. If goal not reached after 6 weeks, add gemfibrozil, 300 mg, twice daily
- Step 6. If goal not reached after 6 weeks, increase gemfibrozil to 60 mg, twice daily
* The goal of therapy is to reach a total cholesterol level of 160 mg/dl or less and a LDL:HDL cholesterol ratio of less than 2.0. Therapies are adjusted based on side effects. Each advance to the next step in the algorithm is made on the basis of two lipid profiles done at least one week apart.
Seventy patients (77%) completed at least 2 years of treatment. Results indicate that the stepped-care drug therapy produced — and maintained — significant improvements in blood lipids over a 2- to 3-year period. Of particular note, adding ENDUR-ACIN® to pravastatin (Steps 2/3) resulted in significant (P<.05) added improvements in LDL and HDL cholesterol levels compared to pravastatin alone (Step 1) (see Table 2).
|Table 2. Mean Percent Change in Blood Lipids in Treatment Group (n=44) Progressing Through Stepped-Care Drug Therapy Steps|
|Step 1||44||42 wk||-22%||+8%||-32%||-15%||-28%||-37%|
|Step 2||40||52 wk||-26%||+17%||-39%||-23%||-35%||-46%|
|Step 3||23||26 wk||-29%||+20%||-44%||-26%||-41%||-53%|
|Step 4||21||33 wk||-25%||+15%||-42%||-2%||-36%||-49%|
|Step 5/6||12||43 wk||-23%||+17%||-34%||34%||-34%||-42%|
|Tx indicates treatment; TC, total cholesterol; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglycerides; TC:HDL, total to high-density cholesterol ratio; LDL:HDL, low-density to high-density cholesterol ratio.|
Common treatment-related side effects included digestive complaints in 26 (59%) patients, skin complaints in 22 (50%) patients, and fatigue and headache in 12 (27%) patients. No patient has elevated liver enzymes greater than three times the upper limit of normal. Three patients (7%) experienced elevated blood glucose over 1.5 times the upper limit of normal.
These findings indicate that a stepped-care, multi-drug therapy that includes ENDUR-ACIN® may offer clinical value in the treatment of patients with established coronary heart disease, especially those who would benefit from aggressive treatment of blood lipids.