SAFETY OF COX-2 INHIBITORS
NONINVASIVE
CHOLESTEROL SKIN TEST
SIBUTRAMINE FOR TREATMENT OF ADOLESCENT OBESITY
FOLIC ACID AND INCIDENCE OF NEURAL TUBE DEFECTS
SAFETY OF COX-2
INHIBITORS
Three new randomized controlled trials bolster evidence of
increased cardiovascular risk associated with COX-2
inhibitors
The New England Journal of Medicine
published three new studies on COX-2 inhibitors and risk
of cardiovascular events on its website a month before the
articles were due to appear in print, citing the studies’
“potential public health implications.” All three studies
are moderate-sized, randomized, placebo-controlled
trials. One study1 was designed to examine the
effect of rofecoxib treatment for three years on the risk
of recurrent neoplastic polyps in the large bowel. This
study of 2,586 patients was terminated early upon finding
increased risk of thrombotic cardiovascular events in the
treatment group compared to the placebo group (relative
risk 1.92, 95% confidence interval 1.19 to 3.11) after 18
months of treatment. However, overall mortality and
cardiovascular mortality were similar in the treatment and
placebo groups.
Another trial2
was also designed to determine the effectiveness of a
COX-2 inhibitor in preventing colorectal adenomas. This
study of 2,035 patients tested two doses of celecoxib (200
mg or 400 mg twice a day) against placebo. The studied
was discontinued after finding a dose-related increase in
cardiovascular mortality in the treatment groups (Hazard
ratio for 200 mg celecoxib vs. placebo: 2.3; 95%
confidence interval 0.9 to 5.5. Hazard ratio for 400 mg
celecoxib vs. placebo: 3.4; 95% confidence interval 1.4 to
7.8).
The
third study3 was designed to test the safety of
valdecoxib and its intravenous (IV) prodrug parecoxib for
treatment of pain after coronary artery bypass grafting.
The 1,671 patients were randomized to receive IV parecoxib
for at least 3 days followed by oral valdecoxib through
day 10; IV placebo followed by oral valdecoxib; or placebo
for 10 days. There was a higher incidence of adverse
cardiovascular events among patients receiving parecoxib
and valdecoxib than among those receiving placebo
(relative risk 3.7; 95% confidence interval 1.0 to 13.5).
These
three studies add to the growing body of evidence that
COX-2 inhibitors are associated with increased risk of
adverse cardiovascular events.
-
Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular
events associated with rofecoxib in a colorectal adenoma
chemoprevention trial. NEJM. 2005 Feb 15; [Epub
ahead of print:
www.nejm.org. Accessed 3/8/2005].
-
Solomon SD, McMurray JJ, Pfeffer MA, et al.
Cardiovascular risk associated with celecoxib in a
clinical trial for colorectal adenoma prevention.
NEJM. 2005 Feb 15; [Epub ahead of print:
www.nejm.org. Accessed 3/8/2005].
-
Nussmeier NA, Whelton AA, Brown MT, et al. Complications
of the COX-2 inhibitors parecoxib and valdecoxib after
cardiac surgery. NEJM. 2005 Feb 15; [Epub ahead
of print:
www.nejm.org. Accessed 3/8/2005].
March 2005 Index
NONINVASIVE
CHOLESTEROL SKIN TEST
A new noninvasive cholesterol skin test has potential as
an office-based screening test for atherosclerosis
At the American College of Cardiology 2005
Annual Scientific Session on March 7, James H. Stein, MD,
presented findings of a small study of a new skin
cholesterol test to assess its potential usefulness in
identifying patients with early, asymptomatic
atherosclerosis. The skin test, called PREVU and marketed
by McNeil Consumer Healthcare, noninvasively measures
sterol in the skin of the palm. It takes less than 5
minutes and does not require fasting, as do serum
cholesterol tests.
Dr. Stein’s study of 81 consecutive
patients (mean age 56 years) found that skin cholesterol
measurements were associated with ultrasound measurements
of carotid intimal-medial thickness. Carotid intimal-medial
thickness was statistically significantly higher among
patients in the highest quartile of skin cholesterol
values compared to the lowest quartile (0.87 mm vs. 0.76
mm; p = 0.011). The association between skin cholesterol
measurements and carotid intimal-medial thickness remained
statistically significant after adjusting for age, sex,
blood glucose, systolic blood pressure, blood lipid
levels, and use of lipid-lowering therapy (p = 0.031) and
after adjusting for Framingham risk score (odds ratio
1.341; 95% confidence interval 1.302 to 1.380, p = 0.048).
The skin cholesterol test is not designed
to replace serum cholesterol tests, but rather, to quickly
and easily identify patients with early, asymptomatic
atherosclerosis in a physician’s office setting. It is
hoped that the test will encourage discussion between
physician and patient about modification of cardiovascular
risk factors.
Peck
P. Noninvasive cholesterol skin test can identify
asymptomatic atherosclerosis. Medscape Medical News
2005.
www.medscape.com/viewarticle/501045_print
Accessed 3/8/2005.
March 2005 Index
SIBUTRAMINE FOR TREATMENT OF ADOLESCENT OBESITY
A small randomized controlled trial suggests that
sibutramine is safe and effective for treatment of obesity
in adolescents.
Researchers at the Catholic University of
Rio de Janeiro, Brazil, conducted a randomized,
double-blind trial of 60 obese adolescents (mean baseline
BMI 36 kg/m2), age 14-17 years, to determine
the safety and effectiveness of sibutramine for weight
loss in this age group. The study involved a 1-month
run-in period during which all subjects received placebo
and a low-calorie diet plus exercise orientation. After 1
month, subjects were randomized to receive sibutramine or
placebo for the next 6 months. Patients in the sibutramine
group had a mean weight reduction of 10.3 +/- 6.6 kg
compared to 2.4 +/- 2.5 kg in the placebo group (p <
0.001). Decrease in mean body mass index was
significantly greater in the sibutramine group (3.6 +/-
2.5 kg/m2) than in the placebo group (0.9 +/-
0.9 kg/m2; p < 0.001). Five times as many
patients in the sibutramine group lost at least 10% of
their baseline weight compared to patients in the placebo
group. Twenty-five percent of patients in the sibutramine
group lost at least 15% of their baseline weight, whereas
none in the placebo group achieved this level of weight
loss.
Study subjects were monitored for adverse
effects, mainly cardiovascular. There were no differences
in heart rate or blood pressure between the two treatment
groups. Among the patients who received echocardiograms
(24 in the sibutramine group and 15 in the placebo group)
at baseline and 24 weeks, there were no significant
differences between groups and no significant changes from
baseline. Constipation occurred in 40% of sibutramine
patients versus 13% of placebo patients. No patients
withdrew because of adverse effects.
While their studied suggests the
sibutramine is safe and effective for treatment of obesity
in adolescents, the authors acknowledge that larger
randomized controlled trials are needed to confirm their
findings.
-
Godoy-Matos
A, Carraro L, Vieira A, et al. Treatment of obese
adolescents with sibutramine: a randomized,
double-blind, controlled study. J Clin Endocrinol
Metab. 2005 Mar;90(3):1460-5. Epub 2004 Dec 21.
-
Barclay L & Lie D. Sibutramine may be safe and effective
for weight loss in obese adolescents. Medscape Medical
News. 2005 Mar 7.
www.medscape.com/viewarticle/501025_print Accessed
3/8/2005.
March 2005 Index
FOLIC ACID AND INCIDENCE OF NEURAL TUBE DEFECTS
International retrospective cohort study finds no
detectable decrease in incidence of neural tube defects
after implementation of folic acid recommendations.
An international group of investigators,
including scientists from the Centers for Disease Control
and Prevention in Atlanta and numerous health agencies in
Europe, performed a retrospective cohort study using
ecologic data to determine the effectiveness of policies
and recommendations on folic acid in reducing incidence of
neural tube defects. The investigators collected
numerator and denominator data from 13 birth defects
registries monitoring rates of neural tube defects from
1988 to 1998 in Norway, Finland, Northern Netherlands,
England and Wales, Ireland, France (Paris, Strasbourg, and
Central East), Hungary, Italy (Emilia Romagna and Campania),
Portugal, and Israel. Countries that fortify their flour
supply with folic acid were excluded. U.S. registries
were originally included in the study but were excluded
when the U.S. began fortifying its flour with folic acid.
Information on folic acid recommendations was collected
from interviews, the published medical literature, reports
of workshops and committees, and documents issued by
governmental agencies and professional bodies.
The investigators compared incidence rates
and trends in rates of neural tube defects before and
after 1992 (the year that the first recommendations were
made and internationally known) and before and after the
year of local recommendations (when applicable). They
failed to find any detectable improvement in incidence
trends for neural tube defects since implementation of
policies and recommendations on folic acid.
The authors note that their findings,
“underscore the ongoing missed opportunities for
prevention well after the publication of the confirmatory
randomised clinical trials [showing effectiveness of folic
acid in reducing incidence of neural tube defects by 80%
or more] and the first public health recommendations.”
Botto LD, Lissi A, Robert-Gnansia E, et al.
International retrospective cohort study of neural
tube defects in relation to folic acid
recommendations: are the recommendations working?
BMJ 2005;330:571 (12 March).
http://bmj.bmjjournals.com/cgi/content/full/330/7491/571?ehom
Accessed 3/14/05.
March 2005 Index
