A dose‐ranging study of a new once‐daily dual‐component drug product containing niacin extended‐release and lovastatin

摘要

Background: Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders, especially those at high risk. Hypothesis: This study evaluated dose‐response relationships and safety of a new dual‐component drug product containing niacin extended‐release (niacin ER) and lovastatin. Methods: The 28‐week double‐blind multicenter trial randomized 237 patients with type IIA or IIB hyperlipidemia to one of four escalating‐dose treatment groups: niacin ER/lovastatin 1,000/20 mg, niacin ER/lovastatin 2,000/40 mg, niacin ER 2,000 mg, or lovastatin 40 mg. Results: Niacin ER/lovastatin was more effective than each of its components for improving levels of low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TG), and exhibited a clear dose‐response effect and additivity across the dosage range. The 2,000/40 dose achieved greater mean reductions in LDL‐C (‐42%) than 1,000/20 (‐28%, p<0.001), lovastatin 40 mg (‐32%, p<0.05), or niacin ER 2,000 mg (‐14%, p<0.05). The 2,000/40 dose was significantly more effective in increasing HDL‐C levels (+ 30%) than the 1,000/20 dose (+ 21%, p = 0.016). The decrease in TG was greater with 2,000/40 (‐43%) than with 1,000/20 (‐26%, p = 0.009). All three niacin‐containing treatments were more effective than lovastatin monotherapy in reducing lipoprotein (a) [Lp(a)] levels. Flushing caused 12 (11%) patients receiving niacin ER/lovastatin and 1 patient receiving lovastatin alone to withdraw. No drug‐related myopathy was noted. One patient each in the 2,000/40 group and the lovastatin 40‐mg group had reversible elevations in liver transaminases. Conclusions: Niacin ER/lovastatin is well tolerated and effective for patients with multiple lipid disorders.