We know that some statins lower LDL more than others. Some raise HDL more than others. What we do not know is whether those differences matter. This study suggests that the differences may be important. Study of Two Cholesterol Drugs Finds One Halts Heart Disease

In patients taking pravastatin, or Pravachol, made by Bristol-Myers Squibb, atherosclerosis worsened slowly over 18 months. But the disease was halted in those who took the highest dose of atorvastatin, or Lipitor, the drug made by Pfizer.

“We saw something extraordinary,” said Dr. Steven Nissen, the cardiologist at the Cleveland Clinic who directed the study of 502 patients.

“All statins are not alike,” Dr. Nissen said, adding that with pravastatin, heart atherosclerosis will worsen, but with the highest dose of atorvastatin, that is unlikely.

At the study’s start, the middle-aged, mostly male heart disease patients in the study had levels of low density lipoproteins, or L.D.L., of 150, on average. L.D.L. carries cholesterol to arteries. Atorvastatin lowered participants’ L.D.L. levels to 79, while those taking pravastatin had an average level of 110.

After 18 months, the atorvastatin patients had no change in the plaque in their arteries. But plaque increased by 2.7 percent in pravastatin patients. The study did not assess patient outcomes like heart attacks and deaths, which would have required 8,000 patients and taken five or more years.

One can also read more details on this study at theheart.org (no direct linking of articles, but it appears in the November 12th entries). This important study deserves several caveats.

• The study compares high dose 80 mg atorvastatin (Lipitor) with moderate dose 40 mg pravastatin (Pravachol). Why do they do this? Why not compare equivalent dosing?
• The maker of Lipitor funded the study. This does not bother me as much as the dosing selection.
• The study measured an intermediate endpoint – atherosclerotic plaque – not clinical outcomes. We must always urge caution from such studies, as the intermediate outcomes will not necessarily result in clinical improvements.
• I cannot find data on HDL in the descriptions of this study (from either the NY Times or theheart.org). Perhaps atorvastatin raises HDL more, thus explaining the effect. I would like to know those data.
• The data show that atorvastatin 80 mg lowers CRP levels greater than pravastatin 40 mg. Since accumulating data have convinced me of the importance of CRP, this information is fascinating.

As most good research does, this study raises as many questions as it attempts to answer. We must always remember that we rarely have definitive answers based on a single study. Rather, we must view clinical knowledge growing in fits and starts, with data accumulating over time.

If I had coronary artery disease, I would probably take atorvastatin 80 mg a day. I can afford it, and it just might help.

I will finish this rant with these quotes from theheart.org.

More information on whether the REVERSAL data do have an effect on clinical outcome will become available soon, with the results of the PROVE-IT study. This trial, in which Cannon and Braunwald are both involved, is comparing the exact same two regimens in REVERSAL but in 4000 ACS patients and has a clinical outcome as the primary end point. Results are expected at the American College of Cardiology meeting next March.

Several other clinical-end-point trials comparing high-dose vs moderate- or low-dose statin treatment are also under way. These include TNT (atorvastatin 80 mg vs atorvastatin 10 mg), IDEAL (atorvastatin 80 mg vs simvastatin 20 mg), and SEARCH (low-dose vs high-dose simvastatin).