Patients treated with high doses of atorvastatin had about a one percent lower annual rate of heart attacks than similar patients receiving usual care, according to a new study in the Nov. 2, 2004 issue of the Journal of the American College of Cardiology.
“The real world concept is the unique feature of the study,” said Michael J. Koren, M.D., F.A.C.C., at the Jacksonville Center for Clinical Research in Jacksonville, Fla. “Most of the work in the study was not done at the research centers; it occurred in managed care organizations, so we got a true reflection of what’s happening in the community, rather than a reflection of what clinical trial centers are capable of doing for patients. At the end of the day, we found that when doctors use the aggressive cholesterol-lowering approach in a real-world setting, there is a significant reduction of cardiovascular events compared to when doctors follow less aggressive practices,” Dr. Koren said.
A total of 2,442 coronary heart disease patients with high cholesterol were randomized to either an aggressive treatment arm using atorvastatin (brand name Lipitor) or usual care. They were followed for 51.5 months on average. Patients in the atorvastatin group were treated with increasing doses of the drug until their LDL cholesterol levels dropped below 80 milligrams per deciliter or until they reached the maximum dose of 80 milligrams per day of atorvastatin. Common starting doses of atorvastatin range from 10 milligrams to 40 milligrams a day.
During the study period averaging just over four years, 4.3 percent of patients in the atorvastatin group suffered a nonfatal heart attack compared to 7.7 percent of the patients in the usual care group. This difference in heart attacks accounted for most of the 4 percent difference in primary outcomes between the two groups (23.7 percent of atorvastatin patients vs. 27.7 percent of those receiving usual care). Dr. Koren said a larger group or a longer study period would have been needed to detect mortality differences.
“There was a strong trend toward fewer cardiac deaths in the aggressively treated patients though this component of the improvement in overall outcomes, 43 deaths in the aggressively treated group versus 61 cardiac deaths in the usual care group, fell slightly outside of a statistically significant range,” Dr. Koren said.
Dr. Koren highlighted the point that this study was not a comparison of drug treatment to placebo. He noted that the advantage observed in the atorvastatin group was on top of any benefits achieved through usual care, including medications, diet and other lifestyle changes. Indeed about two-thirds of the participants were already taking some cholesterol-lowering medication at the time they entered this study. There was no statistically significant difference in reported side effects.
“We saw a big benefit overall for people who were treated aggressively. If you look at all the parameters, there was a 17 percent improvement, but more significantly, if you look at the worst events, there was a 47 percent reduction in those events in patients who were treated aggressively,” Dr. Koren said. “And there was no difference between the two groups in severe myalgias (muscle pain), hospitalizations for side effects or other safety parameters we evaluated. We are not saying that no one gets side effects with these drugs. What we are saying is that when you use these drugs aggressively, the average person in a real-world setting is going to do better overall.”
Dr. Koren said the biggest problem the study encountered was the turmoil in the health care market. As managed care companies failed or merged, the researchers were unable to access some details of participants’ medical records. Nevertheless, he said the study has profound implications for treating cholesterol levels in these patients.
“Doctors need to approach all of their atherosclerosis patients with a plan, meaning that when they come to you, you should have a very specific goal, and you should have a complete commitment to reaching that goal for that patient,” Dr. Koren said.
Funding for this study was provided by Parke-Davis and then Pfizer Pharmaceuticals, the manufacturers of atorvastatin. Dr. Koren said he was involved in all aspects of the study design and execution and that the authors had the final word in the preparation of their article.
Gregg C. Fonarow, M.D., F.A.C.C., at the UCLA Division of Cardiology in Los Angeles, who was not connected with this research, said the results are further evidence that it is feasible and safe to aggressively lower LDL cholesterol with statin medication.