High-Dose Statins Reverse Heart Disease

By ED SUSMAN

Doctors said Monday that high doses of a powerful cholesterol-lowering drug — AstraZenenca’s Crestor (rosuvastatin) — appear to actually reverse the buildup of blockages in arteries that cause heart disease.

Frankly, we were rather surprised that we could do this, said Steve Nissen, chief of cardiology at the Cleveland Clinic. "We have shown before that we could lower cholesterol enough so that we could stop progression of the disease. This time we see regression.

We now know that maximally intensive cholesterol lowering can partially reverse the atherosclerosis disease process, he said.

In an earlier study dubbed REVERSAL, Nissen and colleagues used Pfizer’s Lipitor (atorvastatin) to stop progression of atherosclerosis, the disease that eventually blocks arteries and causes heart attacks, strokes and other cardiovascular diseases.

Results of the two studies have prompted a battle of the statins with Pfizer claiming its drug Lipitor, not Crestor, was the first statin to be shown in studies to reverse arterial plaque.

Pfizer also said in a statement issued Monday afternoon that the two studies cannot be compared since ASTEROID had a single treatment arm and used no comparator drug.

In AstraZeneca’s ASTEROID study testing Crestor — reported at the 55th annual meeting of the American College of Cardiology in Atlanta, Ga. — Nissen treated 349 patients with Crestor for two years to achieve the first reported reversal of atherosclerosis.

He said that patients who completed the trial started with an average of 130 milligrams/deciliter of low density lipoprotein cholesterol — the so-called bad cholesterol that is linked to coronary artery disease development.

After two years on 40 mg of Crestor, those patients had an average level of the LDL cholesterol of 60.8 mg/dL. Overall, Crestor lowered cholesterol about 53 percent.

In addition, the use of Crestor at its highest approved dose increased by an average of 14.7 percent high density lipoprotein cholesterol, the so-called good cholesterol that is responsible for helping the body remove fats, such as LDL cholesterol.

The calculation of how much the disease had regressed was made by using intravascular ultrasound. A tiny ultrasound device is actually threaded into coronary arteries to directly allow for visualization of the plaque’ in the artery walls. The measurement of that plaque before and after the trial showed about a 7 percent reduction in those blockages, which Nissen said was highly statistically significant."

However, Nissen stepped away from endorsing Crestor over Lipitor or any other statin drug. The important thing is not the molecule that we use to lower cholesterol, he told United Press International, but how low we can lower cholesterol.

Nissen — who was the chief investigator of both the Lipitor and Crestor studies — contradicted Pfizer’s claim, saying that the ASTEROID trial he reported Monday was indeed the first to show reversal of atherosclerosis.

He said his patients did not experience any adverse side effects in the study that would give people concern over side effects, and he criticized emphasis placed on possible adverse affects of high doses of the drugs — despite the fact that some rare statin-related toxicities can be life-threatening.

All this angst about statin toxicity is not well-placed, he said, noting that reducing cholesterol can greatly benefit patients at risk of heart disease.

Roger Blumenthal, associate professor of medicine at Johns Hopkins University, Baltimore, Md., said, The results of this study will make all of us more aggressive in treating out patients. We will be trying to get our patients down to an LDL of 60.

Nissen said he will be discussing the findings with his patients, but he said that a single study does not necessarily change clinical practice.