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Houston, TX - Combination therapy with extended-release (ER) niacin and a statin to improve total lipid profile may achieve greater coronary risk reductions than lowering LDL alone, a new study suggests.1
Writing in the May 24, 2004 issue of the Archives of Internal Medicine, the researchers, led by Dr William Insull (Baylor College of Medicine, Houston, TX), explain that statins and niacin have complementary effects. While statins are highly effective at lowering LDL cholesterol, they have lesser effects on HDL cholesterol and triglyceride levels, whereas niacin increases HDL and reduces triglycerides and, to a lesser extent, LDL. It is therefore logical to combine these drugs, with the expectation that effects on clinical events might also be complementary, they note. To reduce side effects of niacin, it is often used in an extended-release form.
They thus conducted a study investigating the effect on serum lipid and lipoprotein levels of different doses of extended-release niacin and lovastatin alone and in combination. In the 26-week trial, 85 men and 79 women were randomized to five parallel treatment arms. Each arm had five sequential four-week treatment periods: niacin ER (starting at 500 mg/day, increasing in 500-mg increments to 2500 mg/day); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg); and three combination arms, each with a constant lovastatin dose and escalating niacin-ER doses.
Results showed that the combination treatment resulted in complementary, dose-dependent changes in all lipid parameters tested. Each drug contributed to the lipid effects in different ways, with lovastatin producing a greater effect on LDL and niacin ER producing greater effects on HDL, triglycerides, and lipoprotein (a). Each 500-mg increase in niacin ER, on average, decreased LDL levels an additional 4% and increased HDL levels 8%. The maximum recommended dose of the combination (2000-mg niacin ER/40-mg lovastatin) increased HDL levels by 29% and decreased LDL levels by 46%, triglycerides levels by 38%, and lipoprotein(a) levels by 14%. All lipid responses were dose dependent and generally additive.
Percent change in LDL-C from baseline with different doses of niacin extended release/lovastatin
|
Niacin ER (mg) |
Lovastatin 0 mg |
Lovastatin 10 mg |
Lovastatin 20 mg |
Lovastatin 40 mg |
|
0 | -19 | -21 | -24 |
|
|
500 | -3 | -21 | -29 | -35 |
|
1000 | -7 | -25 | -32 | -38 |
|
1500 | -12 | -31 | -35 | -43 |
|
2000 | -16 | -34 | -39 | -46 |
|
2500 | -20 | -36 | -36 | -47 |
Percent change in HDL-C from baseline with different doses of niacin extended release/lovastatin
|
Niacin ER (mg) |
Lovastatin 0 mg |
Lovastatin 10 mg |
Lovastatin 20 mg |
Lovastatin 40 mg |
|
0 | 5 | 6 | 9 |
|
|
500 | 3 | 9 | 7 | 11 |
|
1000 | 10 | 18 | 17 | 21 |
|
1500 | 18 | 28 | 24 | 27 |
|
2000 | 29 | 30 | 25 | 29 |
|
2500 | 33 | 37 | 28 | 33 |
Flushing a problem with niacin
Of the patients, 23% taking niacin ER and 18% on the combination discontinued treatment prematurely, compared with 9% taking lovastatin. These differences were due to niacin-related flushing or other cutaneous reactions such as rash or itching. Overall, 62% of patients treated with any niacin-containing formulation reported flushing, as did 15% of those randomized to lovastatin. Discontinuations for adverse events other than flushing were similar across all treatment groups.
Insull et al note that a fixed-dose combination of niacin ER and lovastatin is available and is the first prescription dual-lipid-altering medication to be approved in the US. Marketed under the name Advicor® by Kos Pharmaceuticals, the product comes in three dose combinations500/20 mg, 750/20 mg, and 1000/20 mg. It is not recommended as initial therapy but for patients already taking lovastatin who have low HDL or those already taking niacin who have high LDL.
They conclude: "Combination therapy with niacin and a statin results in favorable changes in all four lipoprotein classes that are independently associated with the risk of developing CHD. Future clinical trials are needed to directly compare combination therapy with niacin and a statin against statin monotherapy to test the hypothesis that such broad control of dyslipidemia will result in greater reductions in coronary risk and will cause regression of arterial lesions of atherosclerosis."
One of the authors of the study, Dr Robin Crouse (Wake Forest University School of Medicine, Winston Salem, NC), commented to heartwire that the combination of niacin and a statin provides "an excellent lipid-altering effect," which would be particularly useful in patients with high LDL and triglycerides and low HDL (combined hyperlipidemia), who tend to be particularly difficult to treat. "In addition, data we have at present testify to the residual risk in secondary prevention even after getting patients to a goal LDL of 100. As well as lowering LDL further, clinical trials using combined therapy (HATS) suggest a high level of efficacy against atherosclerosis progression when a statin is used in combination with niacin," he said.
