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.
“For patients with coronary heart disease receiving ‘usual care’ in a health maintenance organization setting, this study sends a clear message. There is more that you can do to protect yourself from cardiovascular events. By getting and keeping your LDL ‘bad’ cholesterol below 70 to 80 milligrams per deciliter, through daily doses of potent statin therapy in conjunction with lifestyle modification, you can halt the progression or reverse atherosclerotic vascular disease and markedly lower your risk of a fatal or nonfatal heart attack,” Dr. Fonarow said. “The major challenge remains to translate the results of these studies and the national guidelines into routine clinical practice. Currently, only a fraction of the patients that should be on statin treatment are actually being treated with any dose of a statin, and an even smaller fraction of patients are being treated with statin doses that will allow them to achieve optimal lipid levels.”
David T. Nash, M.D., at the State University of New York Health Science Center in Syracuse, N.Y., who also was not part of this research team, said that while the study shows the benefits of statin treatment, it does not highlight other non-drug approaches that may produce similar benefits.
"This is a good study. Nevertheless, we await the results of the Treating to New Targets (TNT) trial for confirmation that lower is better. In addition, it is important to note that the study revealed that there was no mortality benefit for those in the aggressive treatment group. Also, the researchers could have spent some of the money giving people a lower dose of atorvastatin and having everyone see a fitness trainer every three months and a dietician four times a year,” Dr. Nash said.
“So we have here roughly one patient in 25 over four years, or one percent per year, that gets a benefit. In other words you have to treat 100 people to see one benefit. I’m not against that, and given the choice I would take the pill, but I think you have to understand that you don’t have to take the pill the way the authors describe,” Dr. Nash added. “If you just drank orange juice and ate almonds, not tough to comply with, you would get the same difference.”
The American College of Cardiology, a 31,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.