ACC Meeting: Reductions In LDL-C Appear Linked To Reductions In Ischemic Events
NEW ORLEANS, LA -- March 8, 1999 -- Patients in the landmark AVERT
(Atorvastatin Versus Revascularization Treatments) trial who had the greatest reduction
in ischemic cardiovascular events also had the greatest percentage reduction in low
density lipoprotein cholesterol (LDL-C) levels, according to a sub analysis presented
today at the American College of Cardiology scientific session.
The sub analysis showed a 47 percent reduction in LDL-C levels among stable coronary
artery disease (CAD) patients who remained event-free following aggressive
lipid-lowering therapy with Parke-Davis' and Pfizer Inc.'s Lipitor(R) (atorvastatin
calcium). By contrast, patients on Lipitor who did experience a cardiovascular event
(such as nonfatal heart attack, bypass surgery, revascularisation and worsening angina)
had their LDL-C levels reduced by only 35 percent.
"Our analysis of the 164 patients in AVERT who received aggressive lipid-lowering
therapy with Lipitor indicated a relationship between effective reductions in
LDL-cholesterol and reduction in ischemic events," said W. 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,
and a member of the advisory and safety committee overseeing the AVERT trial. "This
correlation was specific to LDL-C and did not relate to other lipid parameters."
The landmark AVERT trial, announced in November 1998, reported a 36 percent
reduction in the combined incidence of cardiovascular events, such as nonfatal heart
attack, bypass surgery, revascularisation and worsening angina in patients given
aggressive lipid-lowering with Lipitor, as compared to patients receiving angioplasty
followed by usual care. These results were clinically important and trended toward
statistical significance.
The trial included 341 patients with stable CAD from 37 centres in the United States,
Canada and Europe, randomised either to 80 mg/day of Lipitor or to angioplasty followed
by usual care (such as stents or statin-therapy). At the time of enrolment, patients in the
AVERT trial had one to two coronary arteries with at least 50 percent narrowing, had no
symptoms or mild to moderate chest pain, relatively normal left ventricular function and
were candidates for angioplasty.
Lipitor has been shown in clinical studies to produce reductions in LDL-C in patients with
elevated cholesterol of 39 percent to 60 percent across the dose range of 10 mg to 80
mg. Reductions in triglycerides of 19 percent to 37 percent 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 two 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. The most frequent adverse effects of atorvastatin are constipation,
flatulence, dyspepsia and abdominal pain. It is recommended that liver function tests be
performed prior to and at 12 weeks following both the initiation of therapy 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). |
