Niacin extended-release therapy in phase III clinical trials is associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events: a pooled analysis.

BACKGROUND AND OBJECTIVE: Niacin is a highly effective agent for increasing low high-density lipoprotein cholesterol (HDL-C) levels. It also has beneficial effects on key pro-atherogenic lipoprotein parameters. However, the side effect of flushing can challenge patient adherence to treatment. In this study, we pooled safety data from available trials of at least 16 weeks' duration to evaluate the impact of flushing on patient adherence to niacin extended-release (NER) therapy. METHODS: Data were pooled from eight NER studies (administered as NER with a maximum dosage of 1000, 1500, and 2000 mg/day, either as monotherapy or in combination with simvastatin 20 or 40 mg/day [NER/S], or lovastatin 20 or 40 mg/day [NER/L]) to evaluate rates of study discontinuation due to flushing or any treatment-related adverse events. RESULTS: While 66.6% of patients experienced flushing, only 5.2% of patients discontinued treatment due to flushing. Of the total number of patients treated with NER (n = 307), NER/S (n = 912), or NER/L (n = 928), 34 (11%), 105 (11%), and 127 (14%) patients discontinued due to any treatment-related adverse event, respectively, while 14 (5%), 43 (5%), and 55 (6%) discontinued due to flushing. Discontinuation for flushing did not differ with regard to maximum dose, or to the presence or type of statin combined with NER. CONCLUSION: Although flushing was common with NER treatment, discontinuation due to flushing occurred in only 5-6% of patients in this pooled analysis. This could be due to several factors, including the fact that all patients in the NER trials were educated about flushing and its management. Translation of methodology employed in these trials into clinical practice may improve long-term adherence to NER therapy, which would enhance the therapeutic benefit of NER for reducing cardiovascular risk.

Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: The SUPREME Study.

BACKGROUND: Aggressive treatment of low-density lipoprotein cholesterol (LDL-C) fails to prevent most cardiovascular (CV) events. Concurrent treatment of LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) should be considered in patients with dyslipidemia. OBJECTIVE: The efficacy and safety of a proprietary niacin extended-release and simvastatin (NER/S) combination were compared to atorvastatin monotherapy in a multicenter, Prospective, Randomized (3:2), Open-label, Blinded Endpoint (PROBE) study. METHODS: Following ≥4 weeks without lipid-modifying therapies, 193 patients with dyslipidemia were treated with NER/S (n = 114; 1000/40 mg/day, weeks 1 to 4; 2000/40 mg/day weeks 5 to 12) or atorvastatin (n = 79; 40 mg/day, weeks 1 to 12). RESULTS: Compared to atorvastatin, NER/S had a larger beneficial effect on HDL-C (primary end point: 30.1 ± 2.3% and 9.4 ± 2.6%, respectively; P <.001), TG (P = .02), and lipoprotein(a) (Lp[a]; P <.001), and similar effects on LDL-C and non-HDL-C. Two-thirds of patients treated with NER/S concurrently attained LDL-C (CV risk-adjusted goals), HDL-C (≥40 mg/dL), and TG (<150 mg/dL) targets, compared to one-third of patients treated with atorvastatin (P <.001). Flushing was the most common treatment-emergent adverse event (TEAE) (67.5% NER/S and 10.1% atorvastatin; P <.001). Seventy-five percent of flushing episodes were mild to moderate. More patients treated with NER/S discontinued due to TEAEs (21.1% and 3.8%; P <.001); the most common TEAE was flushing. CONCLUSION: Compared to atorvastatin, NER/S provided superior improvements in HDL-C, TG, and Lp(a) and comparable improvements in non-HDL-C and LDL-C. Treatment with NER/S should be considered for patients with dyslipidemia requiring comprehensive lipid control.

Fixed-dose combination of extended-release niacin plus simvastatin for lipid disorders.

Coronary heart disease (CHD) carries significant morbidity and mortality worldwide. Elevated LDL-cholesterol and reduced HDL-cholesterol levels are well-recognized CHD risk factors. Despite guideline recommendations for intensive therapy among patients at high risk for CHD to lower LDL-cholesterol, such lowering has failed to prevent approximately two-thirds of cardiovascular events. As a result of new data, guidelines have begun to focus on non-HDL-cholesterol, HDL-cholesterol and triglycerides as treatment targets, with the end result being a recommendation for combination therapy, such as niacin plus statin for the treatment of dyslipidemia. Compared with statin monotherapy, a combination of niacin and statin therapy provides beneficial effects on a broad range of lipid particles and some evidence suggests a further reduction in CHD risk. Recent studies have shown that the combination of a fixed dose of extended-release niacin plus simvastatin reduces non-HDL-cholesterol, LDL-cholesterol, triglycerides and total cholesterol:HDL-cholesterol ratio by approximately 50% while increasing HDL-cholesterol by 25%. The safety of this combination is consistent with the safety profiles of each individual component and is well tolerated. A long-term study is currently being conducted to evaluate whether this combination therapy confers an additive impact on clinical end points.