New investigational combination pill improves multiple cholesterol disorders

Nov 5 2007

Patients treated with a new investigational combination pill showed significant improvements in cholesterol, triglycerides and other key lipids that lead to heart disease, according to results presented at the American Heart Association's Scientific Sessions.

Simcor combines prescription niacin and simvastatin, two FDA-approved medications with established safety profiles, to target good cholesterol (HDL), bad cholesterol (LDL), and triglycerides in a single pill.

“These results indicate that Simcor can go beyond what simvastatin alone can provide,” said principal investigator Dr. Christie Ballantyne, medical director of the Center for Cardiovascular Disease Prevention at the Methodist DeBakey Heart Center in Houston. “This type of combination approach could be an important tool in treating the increasing number of patients with complex lipid disorders, the metabolic syndrome and heart disease.”

Treatment of high cholesterol has historically centered on the use of statins, including simvastatin, to lower LDL cholesterol, which has been the primary target of therapy.

“We now place more importance on comprehensive cholesterol management, including management of HDL levels, in impacting cardiovascular risk,” Ballantyne said. “Medications like Simcor can help patients address multiple problems with one pill.”

Abbott's Simcor, an investigational, fixed-dose combination of Niaspan®, Abbott's extended-release niacin, and simvastatin, met its primary endpoint of lowering non-HDL cholesterol and demonstrating improvements on LDL, HDL and triglycerides. Niacin is known to raise HDL and statins are known to reduce LDL cholesterol and triglycerides.

Research was conducted at the Methodist DeBakey Heart Center and other sites across the nation. Patients in the study treated with a Simcor combination containing 20 mg simvastatin had significantly better reductions in non-HDL (total cholesterol minus HDL) 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 high-dose simvastatin alone, and significant improvements in HDL and triglycerides.

In April, Abbott submitted its New Drug Application to the Food and Drug Administration for Simcor including includes data from this Phase III pivotal SEACOAST trial.

This 24-week double-blind, randomized, controlled 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 SEACOAST 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 26 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 80mg 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 one 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 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. Six percent of patients on Simcor therapy discontinued due to flushing compared to 0.8 percent with simvastatin alone.