Amy Losak Porter Novelli (212) 872-8233
Stephanie Scott Porter Novelli (212) 872-8146
PUBLISHED STUDY SHOWS FLUVASTATIN SLOWS THE PROGRESSION OF CORONARY ARTERY DISEASE IN PATIENTS WITH MILD-TO-MODERATE ELEVATIONS OF CHOLESTEROL(please bold,all caps)
-- Despite Clear Benefits, Those at Risk May Not Be Receiving Treatment --
HOUSTON, AUGUST 5, 1997 -- The first study with fluvastatin sodium (LESCOL)(R) to demonstrate that patients with coronary heart disease and mild-to-moderate elevations of cholesterol can significantly benefit from cholesterol-lowering treatment was published today in the American Journal of Cardiology(please italicize). The study is the first of its kind to demonstrate that treatment in this patient population-which is often not treated with cholesterol-lowering therapy-slows the progression of coronary artery disease.
"Aggressive intervention among patients with mild-to-moderate elevations of cholesterol has been somewhat controversial within the medical community. However, the benefits from treatment shown in the Lipoprotein and Coronary Atherosclerosis Study indicate that even a mild cholesterol elevation may be too high in a patient with evidence of coronary heart disease. These findings could have implications for the millions of coronary heart disease patients who have cholesterol elevations in this range and may not be receiving treatment," noted LCAS investigator Antonio M. Gotto, Jr., MD, DPhil, the Stephen and Suzanne Weiss Dean, Cornell University Medical College, and Provost for Medical Affairs, Cornell University, New York.
The Lipoprotein and Coronary Atherosclerosis Study (LCAS) demonstrated that therapy with the cholesterol-lowering drug fluvastatin slowed progression æ and in some cases produced regression æ of coronary heart disease (CHD) in patients with mild-to-moderate low-density lipoprotein cholesterol (LDL-C) elevations. The LCAS investigators also observed that most of the patients had not received cholesterol-lowering treatment with a HMG-CoA reductase inhibitor, or statin, prior to enrollment in the trial: among patients with lower baseline LDL-C elevations enrolled in LCAS, only 13.1 percent had received treatment with a statin prior to the trial.
A low rate of treatment among patients such as those enrolled in LCAS, may be due to the fact that the effects of cholesterol-lowering in patients with mildly-to-moderately elevated LDL-C have been controversial. The cost of lipid-lowering therapy using a statin has also been a hindrance to treatment. Consequently, many physicians have been reluctant to treat these patients without conclusive evidence of therapeutic benefit from treatment with cholesterol-lowering drugs.
"LCAS confirms the angiographic benefits of statins as well as the need for the treatment of CHD patients with mild-to-moderate LDL cholesterol elevations,"said Dr. Gotto. "Furthermore, cost is a factor that can impact treatment decisions and fluvastatin offers a cost-effective therapy for patients with mildly-to-moderately elevated cholesterol." "
Statistics from the National Health and Nutrition Examination Survey (NHANES III) indicate that 5.5 million Americans with CHD should be treated with cholesterol-lowering drugs under the National Cholesterol Education Program (NCEP) guidelines, yet less than 30 percent of patients in the United States with coronary heart disease are currently receiving lipid-lowering treatment. Even among CHD patients with the highest baseline elevations of LDL-C in LCAS, only 36.1 percent had received treatment with a statin prior to enrollment in the trial.
Slowing the Progression of Coronary Artery Disease
LCAS is the first angiographic trial to demonstrate the benefits of cholesterol--lowering treatment in patients with mild-to-moderate elevations of LDL-C and the first major clinical trial to use coronary angiography--technique used to visualize the heart's blood vessels--to monitor the effectiveness of fluvastatin on the progression of atherosclerosis.
Atherosclerosis is a progressive, degenerative disease in which cholesterol, smooth muscle cells and blood components build up in the inner walls of arteries and form atherosclerotic plaque. The formation of these lesions causes narrowing of the arterial lumen, resulting in the obstruction of blood flow. The obstruction of blood flow to the heart can result in tissue damage or tissue death. Progression of atherosclerosis is associated with higher morbidity and mortality from CHD. According to the World Health Organization, CHD results in 7.2 million deaths per year throughout the world.
In LCAS, fluvastatin patients exhibited significantly less atherosclerotic progression than placebo patients: in all fluvastatin versus all placebo patients, change in minimum lumen diameter was -0.028 mm versus -0.100 mm, respectively.
A similar treatment benefit was demonstrated among patients with lower baseline LDL-C who comprised the monotherapy subgroups (LDL-C < 160 mg/dL or 4.14 mmol/L) and in patients with the lowest pretreatment LDL-C (less than 130 mg/dL or 3.36 mmol/L); change in minimum lumen diameter in this patient population was 0.024 mm with fluvastatin versus 0.094 mm with placebo. An analysis performed in patients with pretreatment LDL-C of 130 mg/dL æ below the NCEP's recommended initiation level for lipid-lowering therapy in adults with CHD æ indicated regression of atherosclerosis among patients treated with fluvastatin. These benefits extended to patients with pretreatment LDL-C as low as 115 mg/dL (2.97 mmol/L).
Among all randomized patients, treatment with fluvastatin increased the proportion of patients with definite regression of atherosclerosis by 76 percent. In monotherapy patients, this increase was 84 percent. In addition, the number of patients with new lesions, as defined in the study, was reduced by 40.5 percent with fluvastatin.
At the end of 2.5 years, LDL-C was reduced by 23.9 percent from baseline in all fluvastatin patients and by 22.5 percent in the fluvastatin only subgroup. The angiographic benefit demonstrated in LCAS indicates that this LDL-C reduction was sufficient to reduce progression--and in some instances induce regression--in patients with mild-to-moderate LDL-C elevations.
"LCAS demonstrates that, in the appropriate patients, fluvastatin clearly has value for slowing the progression of coronary artery disease,"said Dr. Gotto. "These data suggest that the percent reduction in LDL-C may not be the determining factor for therapeutic benefit from lipid lowering, as has been suggested."
Clinical Benefit
Although the study was not designed specifically to detect differences in clinical events, LCAS demonstrated a trend toward benefit. Previous trials have demonstrated that angiographic changes are predictive of clinical coronary events.
Fluvastatin patients required fewer myocardial revascularization procedures (coronary angioplasty, coronary artery bypass grafting, atherectomy, transcatheter revascularization or coronary stent): among monotherapy patients there was a 33.6 percent reduction, while a 35.8 percent reduction was seen in the number of patients requiring any revascularization procedure (myocardial revascularization, carotid endarterectomy, peripheral angioplasty, or peripheral bypass graft). These differences were not statistically significant, but are consistent with reductions seen in other trials.
In terms of safety, fluvastatin therapy was well tolerated by patients and reported side effects were few and comparable to those experienced in the placebo group.
About LCAS
Conducted at Baylor College of Medicine and The Methodist Hospital in Houston, Texas, LCAS was a randomized, double-blind, placebo-controlled trial of 429 patients using 20 mg fluvastatin, twice daily. Because it was considered to be unethical to withhold treatment from placebo patients at known risk, cholestyramine was added to the 25 percent of the study population whose baseline LDL-C was ≥ 160 mg/dL (4.14 mmol/L). The primary endpoint was within patient, per-lesion change in minimum lumen diameter as measured by quantitative coronary angiography at baseline and 2.5-year follow-up.
Patients studied were men and women 35 to 75 years of age (mean age 58.8 years, 19 percent female) with LDL-C of 115-190 mg/dL (2.97 - 4.91 mmol/L) on stable dietary therapy and with coronary heart disease. The mean pretreatment LDL-C was 145.9 mg/dL (3.77 mmol/L).
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Source: The Methodist Hospital
Houston, Texas
Contact: Amy Losak Porter Novelli (212) 872-8233
Stephanie Scott Porter Novelli (212) 872-8146
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