Aggressive Cholesterol Lowering With Lipitor(r) Reduced Cardiac Events New England Journal Of Medicine Study Compared Aggressive Lipid-lowering Therapy With Angioplasty In Patients With Coronary Artery Disease

MORRIS PLAINS, N.J., Jul 8, 1999 /PRNewswire via COMTEX/ -- For the first time, aggressively lowering low density lipoprotein cholesterol (LDL-C, also known as the "bad" cholesterol) with LIPITOR(R) (atorvastatin calcium) tablets to levels below the current U.S. National Cholesterol Education Program (NCEP) guidelines (less than or equal to 100 mg/dL) was shown to be as effective or more effective than angioplasty and usual care in reducing the incidence of cardiovascular events in patients with stable coronary artery disease (CAD), according to research published today in The New England Journal of Medicine. The landmark study, known as AVERT (Atorvastatin Versus Revascularization Treatments), is the first ever to determine the role of aggressive cholesterol reduction in a patient population who were originally candidates for angioplasty.

Aggressive lipid lowering in these patients resulted in a 36 percent (36%) reduction in the combined incidence of cardiovascular events, such as death, nonfatal heart attack, bypass surgery, revascularization, and worsening angina, as compared with patients receiving angioplasty followed by usualcare (p=0.048). Although this difference did not reach the level of significance as adjusted for interim analyses, it did reach the conventional 5 percent level of significance.(1) In addition, patients who received LIPITOR experienced a significant delay in time to the first cardiovascular eventas compared with the angioplasty and usual care group (p=0.027). The study concluded that patients with stable CAD who are candidates for revascularization should be offered the option of aggressive lipid lowering to reduce the incidence of ischemic events.

"These findings should provide physicians with the confidence to more aggressively manage LDL-C reduction to below the NCEP guideline among patients with stable coronary artery disease to help optimize cardiovascular benefits," said Bertram Pitt, M.D., professor of internal medicine at the University of Michigan School of Medicine, Ann Arbor, and chairman of the advisory and safety committee overseeing the AVERT trial. "This study supports the value of getting these patients to levels below 80 mg/dL."

Patients randomized to LIPITOR achieved a mean LDL-C value of 77 mg/dL (2.0 mmol/L), while patients in the angioplasty and usual care group achieved a mean value of 119 mg/dL (3.1 mmol/L). Importantly, AVERT represents the first major lipid-lowering study to achieve a mean of 77 mg/dL, demonstrating that such levels were effectively achieved and well tolerated.

"These data suggest that effective management of patients with stable coronary artery disease should include long-term aggressive lipid lowering," said Virgil Brown, M.D., professor of medicine at Emory University School of Medicine and chief of Medicine and Primary Care Services for the Atlanta Department of Veterans Affairs Medical Center. Dr. Brown served on the advisory and safety committee for the AVERT trial.

The 18-month trial included 341 patients with stable CAD from 37 centers in the United States, Canada and Europe, randomized either to 80 mg/day of LIPITOR or to angioplasty (which may have included stents) followed by usual care (e.g. cholesterol lowering therapy). At the time of enrollment, patients in the AVERT trial had one or two coronary arteries with at least 50% narrowing (mean 80%), had no symptoms or mild to moderate chest pain, relatively normal left ventricular function and were candidates for angioplasty.

AVERT is the first in a series of clinical endpoint studies designed to examine the benefits of aggressive lipid lowering with LIPITOR in a variety of patient populations. Two studies recently launched, TNT (Treating New Targets) and IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid lowering), will evaluate the cardiovascular benefits of aggressive lipid lowering beyond current guidelines. Other studies will examine whether aggressive lipid lowering with LIPITOR can prevent atherosclerotic plaque progression, and whether aggressive lipid lowering benefits other patient groups including stroke patients, post-menopausal women and patients with type 2 diabetes -- a high risk population.

LIPITOR was discovered by Parke-Davis and has been further developed and marketed globally in collaboration with Pfizer. LIPITOR has been shown in clinical studies to produce reductions in LDL-C in patients withelevated cholesterol of 39% to 60% across the dose range of 10 mg to 80 mg. Reductions in triglycerides of 19% to 37% were reported in clinical trials across the same dose range.

LIPITOR is indicated as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. The recommended starting dose of LIPITOR is 10 mg once daily. The dosage range is 10 mg to 80 mg once daily.

LIPITOR is generally well tolerated. Adverse reactions usually have been mild and transient, with fewer than 2 percent of patients being discontinued from clinical trials due to side effects related to LIPITOR. This rate of discontinuation was comparable to that of placebo. In clinical trials, the most frequent adverse effects of atorvastatin were constipation, flatulence, dyspepsia and abdominal pain. It is recommended that liver function testsbe performed prior to and at 12 weeks following both the initiation oftherapy and any elevation of dose, and periodically thereafter. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness and/or marked elevation of creatine phosphokinase (CPK).

Parke-Davis is devoted to discovering, developing, manufacturing and marketing quality pharmaceutical products. Its central research focus ison heart disease, diabetes, infectious diseases, disorders of the central nervous system and women's healthcare. Warner-Lambert is a worldwide company employing more than 43,000 people, and along with Parke-Davis, is headquartered in Morris Plains, N.J.

Pfizer Inc is a research-based, global pharmaceutical company that discovers, develops, manufactures and markets innovative medicines for humans and animals. Pfizer, headquartered in New York City, is celebrating its 150th anniversary in 1999.

For full prescribing information, please call Parke-Davis Medical Affairs at1-800-223-0432.

(1) As a result of two interim analyses, the significance level for the cardiovascular event analyses was adjusted from 0.05 to 0.045.