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J. David Schnatz, M.D.
Director, Lipid Education Service
The Hoffman Heart Institute of Connecticut
Professor of Medicine
University of Connecticut Health Center
Editor's Note: The following article was abstracted from
the News Brief of December, 1997 and January 1998 published by the
Lipid
Education Service of the Hoffman Heart Institute of Connecticut.
Lipid Lessons from the AHA '97
At the recent American Heart Association Meeting,
November 8th�12th 1997, two "Late Breaking Clinical Trials" had to
do with lipid lowering.
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)
The AFCAPS/TexCAPS trial is a primary prevention trial which was
presented by Anthony M. Gotto, M.D. Six thousand five hundred men
and women (15 percent women), ranging in age from 45 to 73 years for
men and 55 to 73 years for women entered the study. Twenty-one percent
were above 65 years of age. Diabetes was present in 2 percent, hypertension
in 22 percent and 12 percent smoked. HDL was less than 35 mg/dl in
35 percent. All patients were free of clinical cardiovascular disease.
LDL ranged from 130 to190 mg/dl, HDL was less than 50 mg/dl and LDL/HDL
less than 5. Mean LDL was 150 mg/dl and HDL 37 mg/dl. LDL was less
than 130 in 81% of participants. Only 17 percent would have qualified
for drugs according to NCEP criteria and 40 percent would not have
had a lipid profile done after screening. Patients were randomized
to placebo or Lovastatin. Lovastatin was titrated to 40 mg to achieve
an LDL of 110 mg/dl. The mean dose of Lovastatin was 30 mg. Cholesterol
decreased 18 percent, LDL 25 percent and TG 15 percent. HDL rose 6
percent. LDL/HDL went from 4.3 to 3.0.
After 4.8 years, the incidence of a first acute major coronary event
was decreased 36 percent (p less than 0.001), and the results in patients
on treatment began to diverge from placebo within the first year.
Primary endpoints of unstable angina, fatal and non fatal myocardial
infarction (MI) and sudden cardiac deaths were reduced 34 percent
in males, 54 percent in females, 28 percent in older participants,
59 percent in smokers, 43 percent in hypertensives and 43% in those
with diabetes mellitus. There were decreases of 35 percent in fatal
and non fatal MIs, 34 percent in hospitalization for unstable angina,
24 percent for all cardiovascular events, 26 percent for coronary
events and 33 percent for revascularization procedures. There was
no significant difference in total mortality and no increase in cancers.
The recommendation was that, in conjunction with diet and exercise,
Lovastatin should be considered in primary prevention candidates where
the LDL is more than 130 and HDL less thsn 50. The authors concluded
that the results support and extend the recommendations of NCEP-II
and that the benefits of statin therapy should be extended to many
patients not currently benefiting from primary prevention.
Long-term Intervention with Pravastatin in Ischemic Disease (LIPID)
The LIPID study is a secondary prevention trial which was presented
by Andrew Tonkin, M.D. It was conducted in 87 centers in New Zealand.
Nine thousand fourteen patients (17 percent females), ranging in age
from 31 to 75 years, were randomized to placebo or Pravastatin. All
had previous acute myocardial infarction or unstable angina, cholesterol
ranging from 155�217 mg/dl and TG <445 mg/dl. Baseline cholesterol
was 219 mg/dl, LDL 150 mg/dl, TG 161 mg/dl, and HDL 37 mg/dl.
After 6 years, cholesterol decreased 18%, LDL 25 percent and TG
12 percent. HDL increased 6%. Two hundred eighty-seven treated patients
died of coronary heart disease in contrast to 373 placebo patients.
Cancer developed in only 126 treated patients in contrast to 142 placebo
patients and violent deaths (trauma or suicide) occurred in only 6
vs 11 placebo patients. The following decreased: coronary heart disease
mortality by 24 percent, total mortality by 23 percent combined fatal
and non-fatal MI by 23 percent, stroke by 20 percent, CABG by 24 percent,
PTCA by 18 percent and unstable angina by 11 percent. There were no
safety concerns.
In this study which complements the CARE study, Dr. Tonkin concludes,
"virtually all patients presenting with myocardial infarction or unstable
angina should now be considered for cholesterol lowering therapy."
Abstracts
Several abstracts presented attracted considerable attention at
the meeting. Two are highlighted below:
Abstract #364: Improved Treatment of Cardiovascular Disease
by Implementation of a Cardiac Hospitalization Atherosclerosis Management
Program: CHAMP. A protocol was initiated at the UCLA Medical Center
to initiate statin treatment in patients with coronary artery disease
prior to discharge from the hospital. Two hundred and fifty-six acute
MI patients from 1992/1993 (control) were compared with 302 acute MI
patients from 1994/1995 (study group). At discharge, 6 percent of the
control and 86 percent of the study group were on statin and at 12 months
the figures were 10 percent and 91 percent, respectively. At 12 months,
the LDL was less than 100 in 6 percent of the control and 58 percent
of the study group. It was recognized that complex patients will need
considerably more effort post hospitalization. Limitations included
the fact that it was not a prospective randomized study, quality of
life, etc. were not assessed, and it was not done in a community setting.
However, this preliminary study was received as a significant advance
in achieving NCEP goals.
Abstract #2306: New data was presented from the Post CABG Clinical
Trial in which 1,351 patients with saphenous vein grafts were treated
aggressively or moderately to lower LDL. Aggressive lowering (AL) achieved
LDL values of 93�97 mg/dl and moderate lowering (ML) achieved LDL of
132�136 mg/dl. Baseline HDL and TG were divided into quartiles and analyzed
as predictors of atherosclerotic progression in the saphenous vein grafts.
When the HDL was less than 35, progression was 30 percent in AL and
47 percent in ML for a Relative Risk (RR) of 0.48. When HDL was more
than 45, progression was 27 percent in AL and 30 percent in ML for an
RR of 0.87. Thus, in relation to HDL quartile, the best reduction in
risk from aggressively lowering LDL was with the lowest baseline quartile
of HDL. When TG was less than 110, progression was 25 percent in AL
and 32% in ML, for an RR of 0.74. When TG was more than 200, progression
was 30 percent in AL and 44 percent in ML, for an RR of 0.56. The higher
the baseline quartile of TG, the better the risk reduction with aggressive
lowering of LDL. The data suggest an alternative approach to raising
HDL in those cases where HDL does not respond to therapy. Aggressively
lowering LDL makes a significant difference, as seen in this study. |
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