X-Message-Number: 23733
Date: Wed, 24 Mar 2004 05:27:02 -0800 (PST)
From: Doug Skrecky <>
Subject: Atorvastatin or policosanol : twin gold standards for CVD treatment

JAMA. 2004 Mar 3;291(9):1071-80.
Effect of intensive compared with moderate lipid-lowering therapy on
progression of coronary atherosclerosis: a randomized controlled trial.

	CONTEXT: Statin drugs reduce both atherogenic lipoproteins and
cardiovascular morbidity and mortality. However, the optimal strategy and
target level for lipid reduction remain uncertain. OBJECTIVE: To compare
the effect of regimens designed to produce intensive lipid lowering or
moderate lipid lowering on coronary artery atheroma burden and
progression. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized
active control multicenter trial (Reversal of Atherosclerosis with
Aggressive Lipid Lowering [REVERSAL]) performed at 34 community and
tertiary care centers in the United States comparing the effects of 2
different statins administered for 18 months. Intravascular ultrasound
was used to measure progression of atherosclerosis. Between June 1999 and
September 2001, 654 patients were randomized and received study drug; 502
had evaluable intravascular ultrasound examinations at baseline and after
18 months of treatment. INTERVENTIONS: Patients were randomly assigned to
receive a moderate lipid-lowering regimen consisting of 40 mg of
pravastatin or an intensive lipid-lowering regimen consisting of 80 mg of
atorvastatin. MAIN OUTCOME MEASURES: The primary efficacy parameter
was the percentage change in atheroma volume (follow-up minus baseline).
RESULTS: Baseline low-density lipoprotein cholesterol level (mean, 150.2
mg/dL [3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL
(2.85 mmol/L) in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the
atorvastatin group (P<.001). C-reactive protein decreased 5.2% with
pravastatin and 36.4% with atorvastatin (P<.001). The primary end point
(percentage change in atheroma volume) showed a significantly lower
progression rate in the atorvastatin (intensive) group (P =.02). Similar
differences between groups were observed for secondary efficacy
parameters, including change in total atheroma volume (P =.02), change in
percentage atheroma volume (P<.001), and change in atheroma volume in the
most severely diseased 10-mm vessel subsegment (P<.01). For the primary
end point, progression of coronary atherosclerosis occurred in the
pravastatin group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P
=.001) compared with baseline. Progression did not occur in the
atorvastatin group (-0.4%; CI -2.4% to 1.5%; P =.98) compared with
baseline. CONCLUSIONS: For patients with coronary heart disease,
intensive lipid-lowering treatment with atorvastatin reduced progression
of coronary atherosclerosis compared with pravastatin. Compared with
baseline values, patients treated with atorvastatin had no change in
atheroma burden, whereas patients treated with pravastatin showed
progression of coronary atherosclerosis. These differences may be related
to the greater reduction in atherogenic lipoproteins and C- reactive
protein in patients treated with atorvastatin.

Eur J Med Res. 2004 Jan 26;9(1):1-17.
Atorvastatin: gold standard for prophylaxis of myocardial ischemia and
stroke - comparison of the clinical benefit of statins on the basis of
randomized controlled endpoint studies.

	AIM: of this study was to compare the clinical benefit - reduction
of heart attacks, strokes or deaths - of the different statins applying
the results of randomized controlled endpoint studies. - METHOD: We
analyzed 11 published randomized controlled endpoint studies
statin-to-placebo looking for the cardiovasculoprotective benefit of the 5
statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin)
MIRACL, 4S, WOSCOPS. - RESULTS: 1. Statins produced substantial benefit
for the patients, reducing the rate of cardiovascular morbidity and
mortality. 2. This benefit was independent of the patient's initial
cholesterol or LDL-cholesterol concentrations and could also be
demonstrated in patients who had average or low cholesterol levels. 3.
Men and women showed a comparable benefit from statin treatment, elderly
patients a little more than younger patients. 4. The statins did not have
like effects. There were clear differences in potency as well as in the
interval between initiation of treatment and the onset of clinical
benefit. 5. Estimating 5 years of treatment, cardiac morbidity decreased
with atorvastatin up to 44 %, with pravastatin up to 36 %, with fluva- or
simvastatin up to 32 % and with lovastatin up to 24 %, approximately. 6.
Estimating 5 years of treatment, morbidity of suffering from stroke
decreased with atorvastatin up to 41 %, with simvastatin up to 34
% and with pravastatin up to 31 %, approximately. For fluva- and
lovastatin there are no comparable data. Within the first 16 weeks of
treatment following an acute coronary syndrome relative risk for
suffering a non-lethal stroke was reduced with atorvastatin 80 mg/day up
to 59 % compared to placebo, the relative risk for stroke up to 50 %. 7.
The fastest onset of clinical benefit - reduction of fatal and non-fatal
cardiovascular events, hospitalization and necessity of invasive
interventions - was demonstrated by treatment with atorvastatin (rapid,
within some weeks), followed by lovastatin (after one year), fluva-,
prava- and simvastatin (after 11/2 - 2 years). 8. These results were
achieved with atorvastatin 10 mg/day (80 mg/day used in MIRACL),
lovastatin 20 to 40 mg/day (caused by dosage titration), pravastatin 40
mg/day, simvastatin 20 to 80 mg/day (caused by dosage titration) or
fluvastatin 80 mg/day. 9. The advantage of atorvastatin may be due to its
ability to reduce cardiovascular disease by stopping the growth of
plaques in artery walls. 10. Atorvastatin was the most powerful compound
in the group of statins, improving patients' health and expectation of
life. - CONCLUSIONS: The authors of the studies agree, that patients at
risk for cardiovascular diseases should be treated with a statin
irrespective of initial cholesterol concentrations, sex or age. If an
acute cardiovascular event has happened, statin treatment should be
initiated early to improve the prognosis of these patients at high risk,
independent from initial LDL cholesterol values. - Summing-up of these 11
trials, the best results and the greatest benefit for the patients were
achieved with atorvastatin, which might be considered to be the gold
standard for prophylaxis of cardiac ischemia and stroke.

(In the over-the-counter category poliocosanol would appear to be the
supplement of choice. Due to greatly reduced risk of side-effects, it
is preferable to statins for CVD preventative purposes.)

Nutr Rev. 2003 Nov;61(11):376-83.
Role of policosanols in the prevention and treatment of cardiovascular

	Policosanols are a mixture of aliphatic alcohols derived from
purified sugar cane. When administered at 5 to 20 mg/day, policosanols
have been shown to decrease the risk of atheroma formation by reducing
platelet aggregation, endothelial damage, and foam cell formation in
animals. Additionally, policosanols have been shown to lower total and
low-density lipoprotein (LDL) cholesterol levels by 13 to 23% and 19 to
31%, respectively, while increasing high-density lipoprotein (HDL)
cholesterol from 8 to 29%. Policosanols are thought to improve lipid
profiles by reducing hepatic cholesterol biosynthesis while enhancing LDL
clearance. When compared with statins, policosanols exhibit comparable
cholesterol-lowering effects at much smaller doses. The mixture is well
tolerated when administered to animals; however, a more precise safety
profile is needed for humans. In summary, policosanols are a promising
resource in the prevention and therapy of cardiovascular disease (CVD),
but these results need to be confirmed in independent laboratories

Drugs Aging. 2003;20(2):153-63.
Comparison of the efficacy and tolerability of policosanol with
atorvastatin in elderly patients with type II hypercholesterolaemia.

	BACKGROUND: Hypercholesterolaemia is a risk factor for coronary
heart disease (CHD). Clinical studies have shown that lowering elevated
serum total cholesterol (TC) levels, and particularly low density
lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of coronary
morbidity and deaths, whereas high serum levels of high density
lipoprotein-cholesterol (HDL-C) protect against CHD. Policosanol is a
cholesterol-lowering drug purified from sugar cane wax with a therapeutic
dosage range from 5-20 mg/day. Atorvastatin is an HMG-CoA reductase
inhibitor which across its dosage range (10-80 mg/day) has shown
significantly greater lipid-lowering effects than all previously marketed
statins. OBJECTIVE: This study was undertaken to compare the efficacy and
tolerability of policosanol with atorvastatin in older patients with type
II hypercholesterolaemia. PATIENTS AND METHODS: This randomised,
single-blind, parallel-group study was conducted in older patients (60-80
years) with type II hypercholesterolaemia. After 4 weeks on a
cholesterol-lowering diet, 75 patients were randomised to policosanol or
atorvastatin 10mg tablets taken once daily with the evening meal for 8
weeks. An interim and final check-up were performed at 4 and 8 weeks,
respectively, after treatment was initiated. RESULTS: At 4 (p < 0.0001)
and 8 (p < 0.00001) weeks, policosanol 10 mg/day significantly lowered
serum LDL-C levels by 17.5 and 23.1%, respectively compared with baseline;
corresponding values for atorvastatin were 28.4 and 29.8%. At study
completion, policosanol significantly (p < 0.0001) reduced serum TC
(16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as
(p < 0.001) triglyceride levels (15.4%). Atorvastatin significantly (p <
0.0001) decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C
(19.8%) ratios, as well as (p < 0.001) triglyceride levels (15.5%).
Atorvastatin was significantly more effective than policosanol in
reducing LDL-C and TC, but similar in reducing both atherogenic ratios
and triglyceride levels. Policosanol, but not atorvastatin, significantly
(p < 0.05) increased serum HDL-C levels by 5.3%. Both treatments were
well tolerated. At study completion, atorvastatin mildly, but
significantly (p < 0.05) increased creatine phosphokinase (CPK) and
creatinine, whereas policosanol significantly reduced AST and
glucose (p < 0.01) and CPK (p < 0.05) levels. All individual values,
however, remained within normal limits. Three atorvastatin but no
policosanol patients withdrew from the study because of adverse events:
muscle cramps (1 patient), gastritis (1 patient) and uncontrolled
hypertension, abdominal pain and myalgia (1 patient). Overall, no
policosanol and seven atorvastatin patients (18.9%) reported a total of
nine mild or moderate adverse events during the study (p < 0.01).
CONCLUSIONS: This study shows that policosanol (10 mg/day) administered
for 8 weeks was less effective than atorvastatin (10 mg/day) in reducing
serum LDL-C and TC levels in older patients with type II
hypercholesterolaemia. Policosanol, but not atorvastatin, however,
significantly increased serum HDL-C levels, whereas both drugs similarly
reduced atherogenic ratios and serum triglycerides. Policosanol was better
tolerated than atorvastatin as revealed by patient withdrawal analysis
and overall frequency of adverse events. Nevertheless, further studies
must be conducted in larger sample sizes and using dose-titration methods
to achieve target lipid levels in order to reach wider conclusions.

Angiology. 2001 Feb;52(2):115-25
A long-term study of policosanol in the treatment of intermittent

	Policosanol is a cholesterol-lowering drug with concomitant
antiplatelet effects. This study was undertaken to investigate the
long-term effects of policosanol administered to patients with moderately
severe intermittent claudication. The study consisted of a 6-week
single-blind, placebo-controlled run in phase, followed by a 2-year
double-blind, randomized treatment step. Fifty-six patients who met study
entry criteria were randomized to receive placebo or policosanol 10 mg
twice daily. Walking distances on a treadmill (constant speed 3.2 km/h,
slope 10 degrees, temperature 25 degrees C) were assessed before and after
6, 12, 18, and 24 months of treatment. Both groups were similar at
randomization. After 6 months of therapy, policosanol significantly
increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7
m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5
+/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the
placebo group (p < 0.01). These effects did not wear off but improved
after long-term therapy, so that final values were 333.5 +/- 28.6 m
(initial claudication distance) and 648.9 +/- 54.1 m (absolute
claudication distance); both significantly greater (p < 0.0001) than
those obtained in the placebo group, which showed values of 137.9 +/-
21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute
claudication distance), respectively. At study completion, 21 policosanol
and 5 placebo patients attained increases in claudication distance values
> 50% (p < 0.001). Policosanol, but not placebo, significantly increased
the ankle/arm pressure index. In addition, from month 6 up to study
completion, the frequency of patients reporting improvement of lower limb
symptoms was greater in the policosanol group than in the placebo group.
The treatment was tolerated well. There were 16 withdrawals (12 placebo,
4 policosanol) from the study. Eight patients in the placebo group
experienced a total of 10 serious adverse events, 8 of which were
vascular events, compared with none in the policosanol group (p < 0.01).
In addition, 3 patients in the policosanol group and 3 patients in the
placebo group reported mild adverse events during the study. The present
results demonstrate the long-term usefulness of policosanol therapy to
treat patients with intermittent claudication.

Angiology. 2003 Jan;54(1):25-38.
Effects of policosanol and lovastatin in patients with intermittent
claudication: a double-blind comparative pilot study.

	Policosanol is a cholesterol-lowering drug with concomitant
antiplatelet effects. The present study was undertaken to compare the
effects of policosanol and lovastatin on patients with moderately severe
intermittent claudication. The study had a 4-week baseline step, followed
by a 20-week double blinded, randomized treatment period. Twenty-eight
patients who met study entry criteria were randomized to policosanol 10
mg or lovastatin 20 mg tablets once daily. Walking distances in a
treadmill (constant speed 3.2 km/hr, slope 10 degrees, temperature 25
degrees C) were assessed before and after 20 weeks of treatment. Both
groups were similar at randomization. Compared with baseline, policosanol
increased significantly (p < 0.01) the initial claudication distance
(ICD) from 160.39 +/- 15.82 m to 211.31 +/- 21.48 m (+33.7%) and the
absolute claudication distance (ACD) (p < 0.001) from 236.39 +/- 25.44 m
to 288.09 +/- 28.47 m (+24.3%); meanwhile both variables remained
unchanged after lovastatin therapy. Changes in ICD and ACD were
significantly larger in the policosanol than in the lovastatin group (p <
0.01). Policosanol, but not lovastatin, significantly increased (p <
0.05) the ankle/arm index, although between-group differences were not
significant. The frequency of patients reporting improvement on quality
of life domains was greater in the policosanol than in the lovastatin
group. Policosanol significantly (p < 0.001) lowered total cholesterol
(TC) and low-density lipoprotein-cholesterol (LDL-C) by 17.5% and 31.0%,
respectively, and meanwhile increased (p < 0.01) high-density
lipoprotein-cholesterol (HDL-C) levels by 31.5%. Lovastatin reduced (p <
0.01) TC (18.0%), LDL-C (22.6%), and (p < 0.05) triglycerides (9.8%). In
addition, policosanol, but not lovastatin, moderately, but significantly,
reduced (p < 0.05) fibrinogen levels, so that final values and percent
changes in both groups were different (p < 0.01). Treatments were well
tolerated. Only 1 lovastatin patient withdrew from the study because of a
nonfatal myocardial infarction. Five lovastatin patients, but none from
the policosanol group, experienced 6 adverse events (AE) (p < 0.01). The
present results indicate that policosanol, but not lovastatin, is a
suitable alternative to manage patients with intermittent claudication
because of pleiotropic properties beyond its cholesterol-lowering effects.

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