Complementary effects of pravastatin and nicotinic acid in the treatment of combined hyperlipidaemia in diabetic and non-diabetic patients.

BACKGROUND

Given that treatment with a single drug is frequently unsuccessful in patients with combined hyperlipidaemia, there is a rationale for the study of regimens using drugs that have complementary therapeutic profiles. We therefore set out to compare the efficacy of a combined pravastatin and nicotinic acid regimen with higher dose monotherapy using either drug in patients with non-insulin-dependent diabetes and in non-diabetic patients with combined hyperlipidaemia.

METHODS

Forty-four patients with total-cholesterol levels of 6.5 mmol/l or higher and triglyceride levels of 2.5 mmol/l or above were randomly assigned to receive either pravastatin alone (40mg/day) or nicotinic acid alone (1500mg/day) for 12 weeks. At the end of this period, the participants received a combination of pravastatin (20mg/day) and nicotinic acid (1000mg/day) for a further 12 weeks. The lipid parameters measured included levels of total cholesterol, triglycerides, low-density-lipoprotein (LDL) cholesterol and high-density-lipoprotein (HDL) cholesterol.

RESULTS

Thirty-three patients (22 without and 11 with diabetes) completed the protocol. Monotherapy with pravastatin was more effective than that with nicotinic acid in reducing levels of total cholesterol (-24.9 versus -9.8%, P<0.001) and LDL cholesterol (-32.1 versus -16.9%, P < 0.01), similar in reducing levels of triglyceride (-28.0 versus -31.8%, NS) and tended to be less effective in elevating levels of HDL cholesterol (+16.4 versus +30.8%, P = 0.06). Combination therapy was more effective than pravastatin monotherapy in reducing levels of triglyceride (-39.3 versus -28.0%, P < 0.05) and elevating those of HDL cholesterol (+35.6 versus +16.4%, P < 0.001) and was equally effective in reducing total-cholesterol (-22.3 versus -24.9%, NS) and LDL-cholesterol (-27.1 versus -32.1%, NS) levels. Combination therapy was more effective than nicotinic acid monotherapy in reducing levels of total cholesterol (-23.8 versus -9.8%, P < 0.001), triglyceride (-39.4 versus -31.8%, P < 0.05) and LDL cholesterol (-35.7 versus -16.9%, P < 0.05) and equally effective in elevating HDL-cholesterol levels (+33.6 versus +30.8%, NS). Diabetic and non-diabetic participants responded similarly to combination therapy. Eleven patients (25%) were withdrawn from the study: nine as a result of nicotinic acid intolerance (flushing and nausea) and one through pravastatin intolerance (nausea); one patient died of a myocardial infarction. Combination therapy elevated glycosylated haemoglobin A1c levels in non-diabetic patients (5.5 to 5.8%, P < 0.001); in diabetic patients, however, the observed rise (7.4 to 7.9%) was not statistically significant. Fasting plasma glucose levels, liver function tests and levels of creatine kinase or uric acid were unaffected by either monotherapy or by combination therapy, with the exception of an elevation of the glucose level in diabetic patients receiving nicotinic acid monotherapy.

CONCLUSIONS

Pravastatin and nicotinic acid in lower-dose combination are more effective than pravastatin alone in reducing levels of triglyceride and elevating those of HDL cholesterol and are more effective than nicotinic acid alone in reducing total-cholesterol triglyceride and LDL-cholesterol levels. Combination therapy is equally effective in type-II diabetic and non-diabetic people. The complementary effects of the combination therapy on lipid levels suggest that this regimen should be considered as a therapeutic option in patients with combined hyperlipidaemia who tolerate the side effects of nicotinic acid.