Aggressive Cholesterol Lowering With LIPITOR(R) Reduced

Cardiac Events Morris Plains, N.J. (PROTEXT) - New England Journal ofMedicine Study Compared Aggressive Lipid-Lowering Therapy withAngioplasty in Patients with Coronary Artery Disease. For the first time, aggressively lowering low densitylipoprotein cholesterol (LDL-C, also known as the "bad"cholesterol) with LIPITOR(R) (atorvastatin calcium) tablets tolevels below the current U.S. National Cholesterol EducationProgram (NCEP) guidelines (less than or equal to 100 mg/dL) wasshown to be as effective or more effective than angioplasty andusual care in reducing the incidence of cardiovascular events inpatients with stable coronary artery disease (CAD), according toresearch published today in The New England Journal of Medicine.The landmark study, known as AVERT (Atorvastatin VersusRevascularization Treatments), is the first ever to determine therole of aggressive cholesterol reduction in a patient populationwho were originally candidates for angioplasty. Aggressive lipid lowering in these patients resulted in a 36percent (36%) reduction in the combined incidence ofcardiovascular events, such as death, nonfatal heart attack,bypass surgery, revascularization, and worsening angina, ascompared with patients receiving angioplasty followed by usualcare (p=0.048). Although this difference did not reach the levelof significance as adjusted for interim analyses, it did reachthe conventional 5 percent level of significance.(1) Inaddition, patients who received LIPITOR experienced a significantdelay in time to the first cardiovascular event as compared withthe angioplasty and usual care group (p=0.027). The studyconcluded that patients with stable CAD who are candidates forrevascularization should be offered the option of aggressivelipid lowering to reduce the incidence of ischemic events. "These findings should provide physicians with the confidenceto more aggressively manage LDL-C reduction to below the NCEPguideline among patients with stable coronary artery disease tohelp optimize cardiovascular benefits," said Bertram Pitt, M.D.,professor of internal medicine at the University of MichiganSchool of Medicine, Ann Arbor, and chairman of the advisory andsafety committee overseeing the AVERT trial. "This study supportsthe value of getting these patients to levels below 80 mg/dL." Patients randomized to LIPITOR achieved a mean LDL-C value of77 mg/dL (2.0 mmol/L), while patients in the angioplasty andusual care group achieved a mean value of 119 mg/dL (3.1 mmol/L).Importantly, AVERT represents the first major lipid-loweringstudy to achieve a mean of 77 mg/dL, demonstrating that suchlevels were effectively achieved and well tolerated. "These data suggest that effective management of patients withstable coronary artery disease should include long-termaggressive lipid lowering," said Virgil Brown, M.D., professor ofmedicine at Emory University School of Medicine and chief ofMedicine and Primary Care Services for the Atlanta Department ofVeterans Affairs Medical Center. Dr. Brown served on the advisoryand safety committee for the AVERT trial. The 18-month trial included 341 patients with stable CAD from37 centers in the United States, Canada and Europe, randomizedeither to 80 mg/day of LIPITOR or to angioplasty (which may haveincluded stents) followed by usual care (e.g. cholesterollowering therapy). At the time of enrollment, patients in theAVERT trial had one or two coronary arteries with at least 50%narrowing (mean 80%), had no symptoms or mild to moderate chestpain, relatively normal left ventricular function and werecandidates for angioplasty. AVERT is the first in a series of clinical endpoint studiesdesigned to examine the benefits of aggressive lipid loweringwith LIPITOR in a variety of patient populations. Two studiesrecently launched, TNT (Treating New Targets) and IDEAL(Incremental Decrease in Endpoints through Aggressive Lipidlowering), will evaluate the cardiovascular benefits ofaggressive lipid lowering beyond current guidelines. Otherstudies will examine whether aggressive lipid lowering withLIPITOR can prevent atherosclerotic plaque progression, andwhether aggressive lipid lowering benefits other patient groupsincluding stroke patients, post-menopausal women and patientswith type 2 diabetes -- a high risk population. LIPITOR was discovered by Parke-Davis and has been furtherdeveloped and marketed globally in collaboration with Pfizer.LIPITOR has been shown in clinical studies to produce reductionsin LDL-C in patients with elevated cholesterol of 39% to 60%across the dose range of 10 mg to 80 mg. Reductions intriglycerides of 19% to 37% were reported in clinical trialsacross the same dose range. LIPITOR is indicated as an adjunct to diet to reduce elevatedtotal-C, LDL-C, apo B, and TG levels in patients with primaryhypercholesterolemia and mixed dyslipidemia. The recommendedstarting dose of LIPITOR is 10 mg once daily. The dosage range is10 mg to 80 mg once daily. LIPITOR is generally well tolerated. Adverse reactions usuallyhave been mild and transient, with fewer than 2 percent ofpatients being discontinued from clinical trials due to sideeffects related to LIPITOR. This rate of discontinuation wascomparable to that of placebo. In clinical trials, the mostfrequent adverse effects of atorvastatin were constipation,flatulence, dyspepsia and abdominal pain. It is recommended thatliver function tests be performed prior to and at 12 weeksfollowing both the initiation of therapy and any elevation ofdose, and periodically thereafter. Myopathy should be consideredin any patient with diffuse myalgias, muscle tenderness orweakness and/or marked elevation of creatine phosphokinase (CPK). Parke-Davis is devoted to discovering, developing,manufacturing and marketing quality pharmaceutical products. Itscentral research focus is on heart disease, diabetes, infectiousdiseases, disorders of the central nervous system and women'shealthcare. Warner-Lambert is a worldwide company employing morethan 43,000 people, and along with Parke-Davis, is headquarteredin Morris Plains, N.J. Pfizer Inc is a research-based, global pharmaceutical companythat discovers, develops, manufactures and markets innovativemedicines for humans and animals. Pfizer, headquartered in NewYork City, is celebrating its 150th anniversary in 1999. For full prescribing information, please call Parke-DavisMedical Affairs at 1-800-223-0432. (1) As a result of two interim analyses, the significancelevel for the cardiovascular event analyses was adjusted from0.05 to 0.045. ots Original Text Service: Parke-Davis and PfizerInc Internet: http://www.newsaktuell.de Contact: Carol Goodrichof Warner-Lambert Co., (USA) 973-540-3620; Vanessa McGowan ofPfizer, (USA) 212-733-3784; or Maura Bergen, (USA) 212-448-4420,or Carol McCormick, (USA) 212-448-4376, both of Ketchum, forWarner-Lambert Company News On-Call:http://www.prnewswire.com/comp/958887.html or Fax, (USA) 800-758-5804, ext. 958887

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