Efficacy and Tolerability of Low-dose Simvastatin and Niacin, Alone and in Combination, in Patients With Combined Hyperlipidemia: A Prospective Trial

Abstract

BACKGROUND: Combination lipid-lowering therapy may be desirable in patients with elevated low-density lipoprotein cholesterol, high triglycerides, and low high-density lipoprotein cholesterol. This study was conducted to determine the lipid-lowering efficacy of the combination of low-dose simvastatin and niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol. METHODS AND RESULTS: In this multicenter, prospective, randomized trial, 180 patients with hypercholesterolemia and hypertriglyceridemia and/or low high-density lipoprotein cholesterol were randomized to combination simvastatin (10 mg/day) and niacin (0.75 g/day) or to either drug alone for 9 weeks. The dose of niacin was doubled (from 0.75 g/day to 1.5 g/day) in both the combination and niacin arms for the remaining 8 weeks. The combination of simvastatin, 10 mg/day, and niacin, 1.5 g/day, reduced total, low-density lipoprotein, and very low-density lipoprotein cholesterol and triglycerides by 24%, 29%, 45%, and 31%, respectively, while increasing high-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol-lowering effect of simvastatin; however, the combination was more effective than either monotherapy at raising high-density lipoprotein cholesterol and lowering very low-density lipoprotein cholesterol (P <.05). More patients discontinued treatment because of an adverse event in the niacin (P <.03) and combination groups (P =.06) than the simvastatin group. CONCLUSIONS: Treatment of patients with combined hyperlipidemia and/or low high-density lipoprotein with combination low-dose simvastatin and niacin resulted in large reductions in total, low-density lipoprotein, and very low-density lipoprotein cholesterol and increases in HDL cholesterol. Although the combination was well tolerated in the current trial, its safety needs to be evaluated in larger trials of longer duration.

A comparative study on the effects of niacin plus atorvastatin with that of fenofibrate plus atorvastatin in dyslipidemia

“…This result was similar to that reported by Stein et al, (1996) who observed that niacin at a dose of 1.5 g administered in combination with simvastatin at a dose of 10 mg per day was highly effective in lowering the serum lipids of triglyceride by 31%, LDL-C by 29% while HDL-C level increased by 31% after 17 weeks of treatment. The greater lipid modifying effects might be due to high doses of niacin and long duration of treatment.…”

“…This study also revealed that combined fenofibrate-atorvastatin appeared more effective than niacin-atorvastatin in reduction of triglyceride. Previously, similar combinations of lipid lowering agents produced qualitatively similar effects in dyslipidemic patients (Stein et al, 1996;Guyton et al, 1998;Athyros et al, 2002;Klosiewicz-Latoszek et al, 2004). However, a study conducted by Deb (2006) where atorvastatin administered in combination with ezetimibe produced significant reduction of LDL-C and total cholesterol, but did not show any significant effect on HDL-C and triglyceride level compared to baseline.…”

What Combination Therapy with a Statin, If Any, Would You Recommend?

“…The first efficacy/safety trial was performed and published with a combination of simvastatin and immediate-release niacin [35]. This trial showed an excellent short-term safety and a remarkable efficacy given by the sum of their effects on lipoprotein fractions, in particular on HDL-C.…”

Does differing metabolism by cytochrome P450 have clinical importance?

“…Reported cases of significant interactions between niacin and statins appear to be in patients with liver toxicity. Combination trials with niacin and lovastatin, simvastatin, pravastatin, and fluvastatin have reported incidence rates of liver enzyme elevations similar to niacin use alone [6,7]. However, these trials were relatively small (less than 100 patients/group) and the patients were well monitored for liver and CPK elevations.…”