Addition of the bile acid sequestrant colesevelam to statin therapy can produce further reductions in low-density lipoprotein cholesterol and high-sensitivity C-reactive protein levels, according to an article in the April 15 issue of the American Journal of Cardiology. Statins used by study participants in the three trials whose data were pooled were simvastatin, atorvastatin, and pravastatin.

These are the first data to demonstrate that the bile acid sequestrant, when added to stable statin therapy, can produce a substantial reduction (6.2 percent) in median high-sensitivity C-reactive protein levels. In contrast, addition of placebo to statin therapy led to a median increase in protein level of 17.2 percent. The difference between treatment groups equates to a significant median reduction of 23 percent.

The data were originally presented at the American Heart Association's Scientific Sessions 2005.

The pooled data for the current analysis were obtained from three randomized, double-blind, placebo-controlled, parallel, multicenter trials (total, 204 patients) conducted in the United States between November 2002 and July 2003. All the patients were at least 18 years old, had a low-density lipoprotein cholesterol level greater than or equal to 100 mg/dL and less than or equal to 250 mg/dL, and triglycerides less than or equal to 300 mg/dL while on drug therapy and had taken stable doses of statin therapy (simvastatin, atorvastatin or pravastatin) for at least four weeks.

The studies involved a total of 204 patients with hypercholesterolemia between the ages of 18 and 75 (mean age. 57; 55 percent female). Pooled analysis demonstrated mean baseline low-density cholesterol levels in the active treatment group and placebo groups were 133 mg/dL and 130 mg/dL, respectively.

The patients in each study were randomized 2:1 to receive either colesevelam 3.75 g/day or matching placebo for six weeks as an add-on to statin therapy. The primary endpoint of each study was the mean percent change from baseline to endpoint in low-density cholesterol. Secondary endpoints were the absolute change in low-density cholesterol, absolute and percent changes in total cholesterol, triglycerides, apo A-1 and apo-B, and absolute change in high-sensitivity C-reactive protein level.

Pooled study results demonstrated that colesevelam plus a statin significantly lowered mean low-density lipoprotein cholesterol more than placebo (16 percent versus 9 percent), while also significantly reducing mean total cholesterol and increasing mean apolipoprotein A-1.

Four times more patients reached the target low-density cholesterol goal of <100 mg/dL with the add-on agent compared to patients who had placebo plus statin (39 percent vs. 10 percent, respectively).

"Bile acid sequestrants were one of the first approved cholesterol-lowering drugs, having been studied in the 1970s, before high-sensitivity C-reactive protein was routinely measured," said lead study investigator Harold E. Bays, MD, FACP, Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY. "This analysis finally brings the past to the present, in that it is the first to show that a non-systemic agent, specifically colesevelam, when added to a statin, statistically reduces high-sensitivity C-reactive protein, an important marker of arterial inflammation."