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Different drugs used to reach cholesterol goal

Thursday, April 03 2008 | Comments

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What's This? By Nancy Stanley

Treating cholesterol to target is the goal of lipid therapy, but reaching that goal is not easy, according to Dr. Frank Ruschitzka, director of preventive cardiology at the cardiovascular center at the University Hospital in Zurich, Switzerland.

"The mainstay of our therapy is statins. And by all means we have to optimize standard treatments in our patients we take care of," he stated. "That's because the alternatives are probably not ready yet."

Statins have been shown to lower LDL cholesterol 20% to 55%, increase HDL cholesterol up to 15%, and lower triglycerides 5% to 30%. However, statins are not tolerated by all patients, and even with dose titration, many patients do not achieve LDL cholesterol goals.

Fortunately, there are other drugs besides statins that can be used to treat dyslipidemia, either alone or in combination with a statin, Dr. Ruschitzka said.

For instance, the drug ezetimibe lowers LDL cholesterol up to 20%, increases HDL cholesterol 2% to 3%, and lowers triglycerides 7% to 8%. Ezetimibe has a different mechanism of action from statins, as it inhibits the absorption of cholesterol. Therefore, "there is substantial interest in ezetimibe's action and we still have to learn even more about that," Dr. Ruschitzka added.

However, as shown in the ENHANCE trial--which compared the effects of ezetimibe plus simvastatin versus simvastatin alone--the additon of ezetimibe does not appear to impact intima-media thickness, although Dr. Ruschitzka noted that this was a surrogate measure.

"I think we should not make too much of the surrogate," he said. "The surrogate is just hypothesis-generating at its best. It can't provide us all the answers. I want to see the endpoint data. We have been too often misled by surrogates.

"We need clinical outcome trials. The real dilemma of ENHANCE is ... that there is no outcome trial there at the moment and it won't become available before the end of this decade ...," he noted.

Dr. Ruschitzka said that, although clinicians need data from large, adequately powered, prospective, randomized clinical trials, they are not available. He added that while clinicians wait for these data, they sometimes look to surrogate trials for information.

In addition, Dr. Ruschitzka noted that resins lower LDL cholesterol 10% to 30%, increase HDL cholesterol up to 10%, but increase triglycerides up to 20%. Niacin, on the other hand, lowers LDL cholesterol 5% to 25%, increases HDL cholesterol 15% to 35%, and decreases triglycerides 20% to 50%.

"Niacin is a good drug," he said, adding that he is waiting for data from endpoint trials comparing niacin with a statin.

Also, fibrates lower LDL cholesterol up to 20%, increase HDL cholesterol up to 15%, and lower triglycerides 25% to 50%.

"The fibrates that are out there are not that overwhelming either [in their effects]," Dr. Ruschitzka noted. "It's not that good [of] an alternative ... particularly since [fibrates] have not been evaluated yet long-term on the background of statin therapy."

Patients who are at high risk for coronary heart disease should have a target LDL cholesterol level <2.6 mmol/L, while those with intermediate risk should have a target LDL cholesterol level <3.4 mmol/L and those at low risk should have a target <4.1 mmol/L.

Further, patients with diabetes should have target triglyceride levels <1.7 mmol/L, and all patients should have a target triglyceride level <5.0 mmol/L. A triglyceride level <10.0 mmol/L should be targeted to prevent acute pancreatitis.

"We want to go for the triglycerides if we have control of LDL [cholesterol]," Dr. Ruschitzka stated.

He noted that if LDL cholesterol is >2.6 mmol/L, the first choice of drug should be a statin at an optimized dose. If there is intolerance to the statin and/or interaction, the next drugs to be used should be a resin, then niacin, then ezetimibe. If the patient is still not at goal, Dr. Ruschitzka recommended combination therapy with a statin plus ezetimibe or a statin plus a resin.

For patients with LDL cholesterol >2.6 mmol/L and triglycerides from 1.7 mmol/L to 5.0 mmol/L, the drug of first choice should also be a statin at an optimized dose. If there is statin intolerance and/or interaction, the next drugs for these patients should be a fibrate then niacin. If the patient is still not at goal, the combination therapy recommended should be a statin plus ezetimibe, a fibrate plus ezetimibe, or a statin plus a fibrate.

For patients who have triglycerides >5.0 mmol/L, the first drug of choice should be a fibrate, followed by niacin and then fish oil.

Combining statins with other drugs may further improve the benefit for patients.

"With a statin alone, we don't get to goal all the time. We fail, as we often do in medicine," he concluded. (Presentation 605-8.)

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