November 4, 2007 — New data released (SEACOAST trial) showed that Abbott's SIMCOR®, an investigational, fixed-dose combination of Abbott's proprietary extended-release niacin, Niaspan®, and simvastatin met its primary endpoint of lowering plaque-promoting non-HDL cholesterol (total cholesterol minus HDL), while demonstrating improvements on other key lipids, LDL "bad" cholesterol, HDL "good" cholesterol and triglycerides.

Patients in the study treated with a SIMCOR combination containing 20 mg simvastatin had significantly better reductions in non-HDL cholesterol compared to 20 mg simvastatin therapy alone, as well as significant improvements in HDL and triglyceride levels. Patients receiving a SIMCOR combination with 40 mg simvastatin experienced reductions in non-HDL comparable to 80 mg simvastatin alone, and significantly better improvements in HDL and triglycerides compared with 80 mg simvastatin alone. Flushing is the most commonly reported side effect associated with Niaspan. It is generally mild and can be lessened by taking aspirin 30 minutes prior to taking the medication at bedtime. Six percent of patients on the combination discontinued therapy due to flushing compared to 0.8 percent with simvastatin alone.

SIMCOR combines two well-established and leading medications, Niaspan and simvastatin, to target multiple lipid parameters – LDL, HDL and triglycerides – in a single pill. Abbott submitted its New Drug Application to the Food and Drug Administration for SIMCOR in April 2007. The submission includes data from the Phase III pivotal SEACOAST trial.

This 24-week trial in more than 600 patients with elevated non-HDL (type II hyperlipidemia or mixed dyslipidemia) compared simvastatin alone to a combination of Abbott's extended-release niacin combined with simvastatin. The study was designed to evaluate the safety and efficacy of the SIMCOR combination following simvastatin monotherapy. Patients enrolled in the trial were assigned to either a low-dose (20 mg) or high-dose (40 mg) simvastatin group. Patients in the low-dose group were randomized to receive Niaspan 2000 mg/simvastatin 20 mg, Niaspan 1000 mg/simvastatin 20 mg, or simvastatin 20 mg. Patients in the high-dose group were randomized to receive Niaspan 2000 mg/simvastatin 40 mg, Niaspan 1000 mg/simvastatin 40 mg or simvastatin 80 mg. Those in the simvastatin control groups received a 50 mg dose of immediate-release niacin to maintain blinding.

Patients in the low-dose group receiving combination treatment achieved 14 percent (1000 mg/20 mg) and 23 percent (2000 mg/20 mg) reductions in non‑HDL compared to a 7 percent reduction with 20 mg simvastatin therapy alone. Additionally, combination treatment resulted in significant improvements in HDL of 18 percent (1000 mg/20 mg) and 25 percent (2000 mg/20 mg) compared to 7 percent with 20 mg simvastatin alone. Similarly, significant reductions in triglycerides of 27 percent (1000 mg/20 mg) and 38 percent (2000 mg/20 mg) were seen in those treated with combination therapy compared to a 15 percent reduction with simvastatin monotherapy.

In the high-dose group, patients treated with SIMCOR combination therapy showed similar (non-inferior) improvements in non-HDL of 11 percent (1000 mg/40 mg) and 17 percent (2000 mg/40 mg) compared to a 10 percent improvement with 80 mg simvastatin therapy alone. Additionally, the high-dose combination group demonstrated significant improvements in HDL of 15 percent (1000 mg/40 mg) and 22 percent (2000 mg/40 mg) compared to a 1 percent decrease among those receiving 80 mg simvastatin monotherapy. Triglyceride levels among the high-dose combinations groups dropped 23 percent and 32 percent, respectively, in contrast to a 0.3 percent increase in those randomized to 80 mg simvastatin monotherapy.

Treatment with the four different doses of Niaspan combined with simvastatin for 24 weeks was well tolerated. There was no evidence for increased risk of hepatotoxicity or myopathy with the combination.

Treatment of high cholesterol has long centered on the use of statins, including simvastatin, to lower LDL cholesterol, which has been the primary target of therapy. Clinical consensus now also emphasizes the importance of comprehensive cholesterol management, including management of HDL levels, in impacting cardiovascular risk.

Niaspan is contraindicated in patients with allergies to any of its ingredients, active peptic ulcer disease, significant or unexplained persistent liver dysfunction, or arterial bleeding. Niaspan should not be substituted for equivalent doses of immediate-release niacin. The most common side effect with Niaspan is flushing of the skin. Other commonly reported side effects include indigestion, headache, pain, abdominal pain, nausea, itching, diarrhea, runny nose, vomiting and rash.

Simvastatin isn't recommended for nursing or pregnant women or who may become pregnant, and anyone with liver problems. The most common side effects are headache, abdominal pain, and constipation.

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