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High Dose Atorvastatin Stops Progression of Disease in Patients With Symptomatic Coronary Artery Disease: Presented at AHA

By Peggy Peck

ORLANDO, FL -- November 12, 2003 -- In a head-to-head trial comparing moderate with aggressive statin therapy aimed at lowering levels of low-density lipoprotein (LDL) to below 80 mg/dL in patients with symptomatic coronary artery disease (CAD), aggressive treatment stopped progression of plaque burden, as measured by intravascular ultrasound (IVUS).

Principal investigator Steven E. Nissen, MD, Cleveland Clinic Foundation, Cleveland, Ohio, United States, presented these results, from the Reversal of Atherosclerosis with Lipitor™ (REVERSAL) study, here on November 12^th during a late-breaking clinical trials session at the American Heart Association's Scientific Sessions 2003.

The study compared pravastatin 40 mg, considered moderate dose statin therapy, with aggressive therapy with atorvastatin. After 18 months of treatment, intravascular ultrasound analysis found zero progression in the group treated with atorvastatin, compared with 2.7% progression in the group treated with pravastatin.

The study randomized 654 patients; 249 patients randomized to pravastatin and 253 to atorvastatin completed the study. The average age of patients was 55 years, more than 70% were men, and 20% were diabetic.

At baseline, the median levels of total cholesterol, LDL, high-density lipoprotein (HDL), and triglycerides in both treatment arms were 233 mg/dL, 150 mg/dL, 43 mg/dL, and 198 mg/dL, respectively.

After 18 months, the values in the pravastatin arm were 188 mg/dL, 110 mg/dL; 45 mg/dL, and 166 mg/dL, respectively, which corresponded to percent changes of -18.4% for total cholesterol; -25.2% for LDL; +5.6% for HDL, and -6.8 for triglycerides.

In the atorvastatin arm, changes after 18 months of therapy were -34% for total cholesterol, -46% for LDL, +2.9% for HDL, and -20% for triglycerides. Results for total cholesterol, LDL, and triglycerides were significant (total cholesterol and LDL at P < .0001 and triglycerides P < .0009).

Dr. Nissen said that when the study was initiated, "I was quoted as saying 'It's the LDL, stupid.' I was only partly right; it was the drug as well." Moreover, he said that atorvastatin stopped plaque progression in each of 22 pre-determined subgroups, while "we were unable to stop progression in any of the subgroups in the pravastatin arm." Pravastatin did not stop plaque progression, even when it achieved LDL reductions similar to those achieved by atorvastatin.

Patients in the atorvastatin arm also achieved much greater reductions in C-reactive protein levels compared with pravastatin -- 36.4% versus 5.2%. This potent anti-inflammatory effect might be a factor in the observed result differences between the two treatments, he said.

The results are robust enough, Dr. Nissen said, that he is changing his clinical practice, but he is not yet ready to make a clinical recommendation because there are no clinical outcomes to support the intravascular ultrasound data.

Raymond J. Gibbons, MD, professor of medicine, Mayo Clinic Medical School, Rochester, Minnesota, United States, said in an interview that it is premature to make any clinical recommendations. "We practice evidence-based medicine and evidence-based medicine tells us that statins as a class reduce mortality and morbidity," Dr. Gibbons said.


[Study title: Comparison of Intensive Vs. Moderate Lipid Lowering on the Progression Of Coronary Artery Atherosclerosis Measured By Intravascular Ultrasound: A Randomized Controlled Trial. Late breaking clinical trials.]

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