Full text of DOI:10.2165/00003495-200262120-00001

Drugs 2002; 62 (12): 1707-1715
0012-6667/02/0012-1707/$30.00/0
CURRENT OPINION
© Adis International Limited. All rights reserved.
Who Should Receive HMG CoA
Reductase Inhibitors?
Koon K. Teo1 and Jeffrey R. Burton2
1
2
Division of Cardiology, McMaster University, Hamilton, Ontario, Canada
Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada
During the last decade, the development of the HMG CoA reductase inhibitors,
commonly referred to as ‘statins’, has contributed greatly to cholesterol lowering
therapy and cardiovascular risk reduction. These agents are well tolerated and
efficacious. Data on nearly 30 000 patients from five long-term randomised,
placebo-controlled trials of statins have clearly demonstrated that a broad range
of individuals can benefit from such therapy. These include men or women,
younger or older individuals, those with elevated or normal cholesterol levels, with
or without myocardial infarction or symptomatic coronary heart disease, with or
without hypertension or diabetes mellitus, and those who are smokers or non-
smokers. Benefits include reductions in the risks for myocardial infarction, and
coronary, cardiovascular and all-cause mortality, stroke and the need for coronary
revascularisation. Results of the recently completed Heart Protection Trial have
clearly confirmed the results of the earlier trials and support the use of statin
therapy in secondary prevention. The role of statins in acute coronary syndromes
is being actively evaluated and appears promising. In primary prevention, the
data are not as convincing and generalisations cannot be made as to whether, and
in which subgroup, drug therapy to lower low density lipoprotein (LDL) choles-
terol should be initiated. There are important cost implications to consider and
the use of statin therapy has to be judged on an individual basis, particularly in
those with high or very high LDL cholesterol levels and/or with multiple risk
factors rendering them at high short- and long-term risk of coronary heart disease.
There is evidence of a ‘care gap’ in translating trial data into practice, even in
secondary prevention, and this needs closing in order to improve patient outcomes.
Abstract
During the last decade, the development of the
ease in individuals with elevated or normal choles-
terol levels. The link between lipid levels and risk
of cardiovascular disease is now widely accepted.
Preventive measures are commonly used in indi-
viduals at risk. This has not always been the case.
Although earlier trials of less efficacious and
less well tolerated cholesterol lowering agents have
shown that high-risk individuals with high choles-
terol levels benefited from cholesterol lowering
therapy, the results of many of these trials were
HMG CoA reductase inhibitors, commonly re-
ferred to as ‘statins’, has contributed greatly to cho-
lesterol lowering therapy and cardiovascular risk
reduction.[1,2] Extensive research has demonstrated:
(i) the mechanistic role of lipids in atherosclerosis
formation; and (ii) the epidemiology of cholesterol
as a cardiovascular risk factor. Clinical trials have
shown that lipid lowering therapy reduces morbid-
ity and mortality secondary to coronary artery dis-

1708
Teo & Burton
inconclusive, particularly for individuals with
mildly elevated or normal cholesterol levels.[3,4]
There were controversies as to whether it was safe
to lower cholesterol levels so much (total choles-
terol <5.20 mmol/L) in this latter group.[4] With the
introduction of the statins and the completion of
several key clinical trials with these agents, the
benefits of cholesterol lowering have been conclu-
sively shown in individuals at risk.[5-9] With two
exceptions,[8,9] these were carried out as secondary
prevention trials. Concurrent angiographic studies
and animal and laboratory studies have corrobo-
rated the results from the clinical trials and have
provided insights into the mechanisms of the ben-
efits of statin therapy.[10-16]
The issues now are not whether treatment with
statins is beneficial but who should be treated and
whether such treatment would reduce the risk of
other clinical events besides those that can be di-
rectly attributed to coronary heart disease. Until
recently, there was a debate as to whether there is
a threshold level below which low density lipopro-
tein (LDL) cholesterol lowering is not beneficial.
This has been settled with the completion and re-
port of the Heart Protection Trial.[17] There are also
suggestions that other mechanisms of action of the
statins, besides cholesterol lowering, may have
contributed to the benefits seen in these trials. A
review of the results from the major trials and other
studies will answer some of these questions.
Statins lower cholesterol levels by suppression
of hepatic cholesterol synthesis, leading to an in-
crease in hepatic LDL receptors and an alteration
in the formation of very-low-density lipoprotein
(VLDL) particles. The commonly available statins
include lovastatin, pravastatin, simvastatin, fluva-
statin and atorvastatin. A fifth, cerivastatin, has been
withdrawn from the market recently because of
an excess of adverse effects. Many studies have
shown that the efficacy of these agents in lowering
LDL cholesterol varies greatly when using publish-
ed recommended doses. Only three of these agents,
simvastatin, pravastatin and lovastatin have been
used in published major clinical trials (see section
1).[5-9] While the evidence supports the view that
the benefits of the statins are probably a class ef-
fect, differences among agents cannot be easily re-
solved in the absence of large ‘head to head’ com-
parative trials. Nevertheless, there is more than
adequate information from this large database to
draw useful conclusions.
1. Clinical Trials
Five key, adequately powered, long-term clini-
cal outcomes trials have been conducted and these
have exerted the greatest impact on clinical prac-
tice (table I). They are the three secondary preven-
tion trials, the Scandinavian Simvastatin Survival
Study (4S),[5] the Cholesterol and Recurrent Events
(CARE) trial[6] and the Long-term Intervention
with Pravastatin in Ischaemic Disease (LIPID)
trial,[7] and the two primary prevention trials, the
West of Scotland Coronary Prevention Study (WOS-
COPS)[8] and the Air Force/Texas Coronary Athero-
sclerosis Prevention Study (AFCAPS/TexCAPS).[9]
A number of angiographic trials have also been car-
ried out evaluating the effects of statin treatment
on the progression of coronary atherosclerosis and
their results are in concordance with the major clin-
ical trials.[10-16]
The spectrum of the 29 820 patients enrolled in
these five trials ranged from high-risk patients with
myocardial infarction and/or unstable angina pec-
toris and with cholesterol levels up to 8.0 mmol/L
to those without clinical evidence of vascular dis-
ease and normal cholesterol levels (table I). In
these trials, LDL cholesterol levels were reduced
by approximately 25 to 35% during the long-term
follow-up of 5 to 6 years. The primary trial end-
points varied among the trials, since the choice of
primary endpoint in any trial is greatly influenced
by the sample size, the duration of treatment and
the baseline risk profile of the patients. Thus, the
primary endpoints were: total all cause mortality
in the 4S trial; a composite of coronary heart dis-
ease mortality or non-fatal myocardial infarction
in the CARE trial; coronary heart disease mortality
in the LIPID trial; a composite of coronary heart
disease mortality or non-fatal myocardial infarc-
tion in WOSCOPS; and a composite of fatal or
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Drugs 2002; 62 (12)

Who Should Receive Statins?
1709
Table I. Summary of baseline characteristics of patients enrolled in five major randomised, placebo-controlled clinical trials of HMG Co-A
reductase inhibitors
Variables
4S[5]
CARE[6]
LIPID[7]
WOSCOPS[8]
AFCAPS/
TexCAPS[9]
No. pts
4444
4159
9014
6595
5608
Start date
May 1988
Aug 1994
5.4
Dec 1989
Feb 1996
5.0
Jun 1990
Feb 1989
May 1995
4.9
May 1990
Sep 1997
5.2
Completion date
Average follow-up (y)
Active treatment (mg/day)
Average age (y)
Female (%)
Sep 1997
6.1
Simvastatin 20-40 Pravastatin 40
51% ≥60a
Pravastatin 40
Pravastatin 40
55
Lovastatin 20-40
58
59
14
100
20
21
43
15
28
32
54
62
17
64
36
10
42
9
19
79
38
27
26
5
0
b
15
c
MI (%)
c
UAP (%)
5b
44
15
1
Current smoker (%)
Hypertension (%)
Diabetes mellitus (%)
PTCA alone (%)
CABG alone (%)
PTCA or CABG (%)
12
22
4
11
27
35
8
Concomitant medication (%)
Aspirin
37
57
30
83
39
38
14
82
47
36
16
17
5
β-Blockers
Calcium channel antagonists
ACE inhibitors
5
8
Lipid levels mmol/L (% change)d
Total cholesterol
6.75 (–25)
4.87 (–35)
1.19 (+8)
1.51 (–10)
5.40 (–20)
3.60 (–28)
1.01 (+5)
1.75 (–14)
5.64 (–18)
3.88 (–25)
0.93 (+5)
1.56 (–11)
7.03 (–20)
4.97 (–26)
1.14 (+5)
1.85 (–12)
5.71 (–18)
3.89 (–25)
0.94 (+6)
1.78 (–15)
LDL cholesterol
HDL cholesterol
Triglycerides
a
b
c
d
51% of patients in 4S were 60 years of age or older, suggesting a median age of just over 60 years.
None of the patients had a history of MI, but 5% had stable angina pectoris not requiring hospitalisation during previous 12 months.
Patients with MI, angina pectoris or other clinical vascular disease were excluded.
Percent change from baseline in patients on active treatment or comparison of lipid levels between active and placebo groups during
the trial.
4S = Scandinavian Simvastatin Survival Study; ACE = angiotensin converting enzyme; AFCAPS/TexCAPS = Air Force/Texas Coronary
Atherosclerosis Prevention Study; CABG = coronary artery bypass graft surgery; CARE = Cholesterol and Recurrent Events; HDL = high
density lipoprotein; LDL = low density lipoprotein; LIPID = Long-term Intervention with Pravastatin in Ischaemic Heart Disease; MI =
myocardial infarction; PTCA = percutaneous transluminal coronary angioplasty; UAP = unstable angina pectoris; WOSCOPS = West of
Scotland Coronary Prevention Study.
non-fatal myocardial infarction, unstable angina or
sudden cardiac death in AFCAPS/TexCAPS. In
each trial, a clear and consistently significant re-
duction in risk of the primary endpoint was found
in patients on active treatment compared with pla-
cebo.[5-9]
ductions were seen in myocardial infarction, in
deaths from coronary heart disease, cardiovascular
or all-causes, in stroke and in the need for revasc-
ularisation in the patients receiving statins com-
pared with controls. These data can be interpreted
as indicating that statin therapy is beneficial in a
wide range of patients, irrespective of gender, age,
cholesterol levels, smoking status, or history of
As summarised in table II, statistically signifi-
cant, or strong trends toward significant, risk re-
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Drugs 2002; 62 (12)

1710
Teo & Burton
Table II. Relative risk reductions (95% confidence interval) in clinical outcomes in five major randomised, placebo-controlled clinical trials of
HMG Co-A reductase inhibitors
Outcome
4S[5]
CARE[6]
LIPID[7]
WOSCOPS[8]
31 (15-45)
AFCAPS/
TexCAPS[9]a
Non-fatal MI
Any MI
37 (27-46)
23 (8-39)
25 (8-39)
29 (18-38)
40 (17-57)
Mortality from:
CHD
42 (27-54)
35 (20-40)
5 (–41-37)
30 (15-42)
30 (4-48)
20 (–5-39)
15 (–11-35)
11 (–22-35)
9 (–12-26)
27 (15-37)
31 (3-52)
24 (12-35)
25 (13-35)
28 (–10-52)
32 (3-53)
CV
non-CV
11 (–28-38)
22 (0-40)
all-cause
Stroke
22 (13-31)
19 (0-34)
20 (10-28)
11 (–11-40)
37 (11-56)
Revascularisation
37 (26-46)
33 (15-48)
a
Significant reductions were found in the primary composite endpoint of first major coronary event (fatal or non-fatal MI, unstable angina
pectoris or sudden cardiac death) and other cardiovascular events.
4S = Scandinavian Simvastatin Survival Study; AFCAPS/TexCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study; CARE
= Cholesterol and Recurrent Events; CHD = coronary heart disease; CV = cardiovascular; LIPID = Long-term Intervention with Pravastatin
in Ischaemic Heart Disease; MI = myocardial infarction; WOSCOPS = West of Scotland Coronary Prevention Study.
hypertension, diabetes mellitus, myocardial infarc-
tion, or the presence or absence of coronary disease
symptoms.
diabetes or hypertension.[18] Significant relative
risk reductions were seen in the various pre-defined
categories of baseline lipid levels.[18] Subgroup
analyses from the 4S trial confirm these find-
ings.[5,18-21]
In the interpretation of trial data, whether or not
some patients with some particular baseline char-
acteristics will benefit from statin therapy can be
determined by subgroup analysis. However, such
analyses can be fraught with statistical type I and
type II errors, and any results should be interpreted
cautiously. In randomised trials, the reliable detec-
tion of modest, but important, differences between
active and control treatments requires large num-
ber of patients and events. To further detect signif-
icant treatment differences between subgroups,
substantially more patients are required. No study
is designed such that there is adequate power to
reliably detect subgroup differences. To overcome
this concern about lack of statistical power, pool-
ing of the data from several trials has been carried
out and data from other trials can be examined for
consistency of outcomes. A formal analysis of the
pooled data from the three pravastatin trials (CARE,
LIPID and WOSCOPS) has reported that active
treatment in these trials significantly reduced the
risk of coronary heart disease death or nonfatal
myocardial infarction in younger (<65 years) and
older (≥65 years) patients, men and women, smok-
ers and non-smokers, and patients with and without
The 4S trial, which included patients with
higher cholesterol levels than those in the other
trials, reported similar treatment sizes were seen in
the patients regardless of baseline cholesterol lev-
els,[5] whereas the CARE trial suggested that pa-
tients with baseline LDL cholesterol levels lower
than 3.25 mmol/L did not benefit from treatment.[6]
This latter observation has not been confirmed in
other trials. It may be that individuals with these
low baseline levels were at a much lower risk and
therefore that the sample size in this particular sub-
group did not have sufficient statistical power to
show a difference between the active and control
groups. Another explanation may be that there re-
ally is a biological basis for the apparent lack of
effect.[22] On balance, the former explanation is
more likely. In general, in these trials, the likeli-
hood of benefit is greater in the secondary preven-
tion trials enrolling higher risk patients, than in
the primary prevention trials that enrol lower risk
patients. In the primary prevention trials, the
WOSCOPS trial, which enrolled higher risk pa-
tients, showed a greater likelihood of, and larger
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Drugs 2002; 62 (12)

Who Should Receive Statins?
1711
absolute, benefit than in the AFCAPS/TexCAPS
trial which evaluated lower risk patients.
with hypertension and those without, individuals
with diabetes and those without, smokers or non-
smokers, and those with or without advanced le-
sions.[16] These data are clearly consistent with the
overall data from the clinical trials with clinical
endpoints.
The contribution of statins appears promising in
patients with acute ischaemic syndromes. The
Myocardial Ischemia Reduction with Aggressive
Cholesterol Lowering (MIRACL) study random-
ised 3086 patients to atorvastatin 80 mg/day or pla-
cebo 24 to 96 hours after an acute ischaemic syn-
drome.[23] After a follow-up period of up to 16
weeks, the difference in the primary composite
outcome of death, nonfatal myocardial infarction,
cardiac arrest with resuscitation, or recurring symp-
tomatic myocardial ischaemia with objective evi-
dence and requiring emergency hospitalisation be-
tween the atorvastatin group (14.8%) and the
placebo group (17.4%) was nominally significant
(p = 0.048). There were no significant differences
between the groups for each of the individual end-
points except for a significantly lower risk in
symptomatic ischaemia requiring hospitalisation
(6.2 vs 8.4%, p = 0.02).[23] Several ongoing trials
are currently actively evaluating the role of the
statins in acute ischaemic syndromes.
The Heart Protection Trial, the preliminary re-
sults of which were reported at the American Heart
Association Annual Scientific Meeting in Novem-
ber 2001, studied the effects of simvastatin 40
mg/day and antioxidant vitamin supplementation
on mortality in a wide range of 20 536 patients at
high risk of coronary heart disease, that is, those
with previous myocardial infarction or other coro-
nary heart disease, other occlusive non-coronary
atherosclerotic disease, diabetes or hypertension.[17]
At baseline, 42% of patients had LDL cholesterol
levels of ≥3.5 mmol/L, 25% had levels between 3.0
and 3.5 mmol/L and 33% had levels <3.0 mmol/L.
In addition, 24% of the patients were between 65
and 69 years of age and 28% were 70 years or
older. While the vitamin supplementation had a
neutral effect on outcomes, treatment with simva-
statin was associated with a highly significant 17%
relative risk reduction in vascular mortality (p <
0.0002) and a 12% reduction in all cause mortality
(p < 0.001). Stroke was reduced by 27% (p <
0.00001). Highly significant reductions are seen
in the major pre-specified subgroups of those pa-
tients with myocardial infarction, those without
coronary heart disease but with cerebrovascular
disease, peripheral vascular disease or diabetes.
Similar reductions in risk of vascular events after
treatment with simvastatin were seen in male and
female patients, and in all age groups, that is, in
those who were younger than 65 years, 65 to 69
years, 70 to 74 years and those 75 years or older.
Comparable benefits were also seen in patients ir-
respective of their baseline LDL cholesterol levels.
Thus, this trial confirms the finding from the
earlier trials. A consistent finding is that high-risk
patients benefit from statin therapy irrespective of
gender, age and baseline LDL cholesterol levels.
Unlike a previous trial suggesting that there is a
level of LDL cholesterol (3.25 mmol/L) below
2. Angiographic Trials
Angiographic trials of cholesterol lowering
therapy have also shown consistently that patients
randomised to active treatment benefited with a
slowing of progression, or even an enhancement of
regression, of coronary atherosclerosis.[10-16] Early
coronary angiographic trials enrolled only patients
with high cholesterol levels.[10-12] More recent tri-
als have enrolled patients with moderately ele-
vated levels.[13-16] One trial has reported a neutral
effect on angiographic endpoints in patients with
normal cholesterol levels,[24] but another with a
larger sample size and longer follow-up showed
clearly that patients with normal or slightly ele-
vated cholesterol levels clearly benefited angio-
graphically from long-term (average follow-up of
4 years) statin therapy.[15]
Subgroup analysis of the data from the latter
trial also showed convincingly that the benefits
could be seen in important subgroups including
men or women, younger or older individuals, those
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Drugs 2002; 62 (12)

1712
Teo & Burton
which further LDL cholesterol lowering is not as-
sociated with benefits,[6] this trial showed that even
in patients with LDL cholesterol levels which are
3.0 mmol/L or less, benefits of treatment can be
obtained.
appears interesting, their contribution to the clini-
cal benefits remains to be demonstrated.
5. Cholesterol Lowering Therapy in
Clinical Practice: Primary versus
Secondary Prevention
3. Other Outcomes
The data have thus far been reviewed in terms
of risk levels. Data from the trials have shown that
individuals at high risk of developing cardiovascu-
lar disease such as those enrolled in the 4S, derived
greater benefits from statin therapy than the pa-
tients at lower risk in the AFCAPS/TexCAPS. In
clinical practice, it is more usual to make decisions
about drug cholesterol lowering therapy in terms
of primary or secondary prevention. Most of the
data demonstrating the effectiveness of statin ther-
apy have been obtained from trials of secondary
prevention. Only the data from WOSCOPS and
AFCAPS/TexCAPS are available on primary pre-
vention. Whether or not drug therapy should be
initiated in primary prevention remains controver-
sial.[31] Because of the smaller number of lower
risk individuals who experienced fewer events in
these two trials, data from subgroup analyses as to
whether particular subgroups would benefit from
treatment remain inconclusive. This is in contrast
to secondary prevention trials, in which convinc-
ing data show that a broad range of individuals will
benefit from treatment. It has been pointed out that
a decision to initiate statin therapy as primary pre-
vention in an individual may be guided by data
from cost effectiveness analyses.[31] While this is
logical, for the practising physician, such analyses
may not be readily available nor specifically appli-
cable to the individual situation and there is no
simple guide from the trial data with which to help
with decision making. The Third Report of the Na-
tional Cholesterol Education Program (NCEP III)
has adopted an approach that appears reason-
able.[32]
Interpretation of the data on the effects of statin
treatment on other outcomes must be qualified by
the comments on subgroup analysis. However,
statin treatment has also been consistently ob-
served to reduce the incidence of stroke and the
need for revascularisation in the trials discussed
here (table II). While reduction of the need for
revascularisation may be seen to be part of the
‘anti-atherosclerosis’ effect of statins, it is less
easy to explain the reduction in stroke risk.
Stroke and coronary heart disease share many
of the same risk factors, but the correlation be-
tween cholesterol levels and either ischaemic or
haemorrhagic stroke has been shown to be weak.[25]
That statin therapy can reduce the incidence of
stroke by approximately 30%[25] can perhaps be
attributed to anti-atherosclerotic effects or to other
mechanisms of the statins.
4. Other Mechanisms of Benefit
from Statin Therapy
Several studies have suggested that statins are
associated with a number of potential mechanisms
of benefit other than cholesterol lowering. These
include anti-inflammatory and antiatherothrom-
botic properties.[26-28] It has been suggested that
the reason the clinical benefits of statin therapy are
much greater than that which could be extrapolated
from the effects of the treatment on angiographic
endpoints may be due to these mechanisms, which
are unrelated to cholesterol lowering. However,
other investigators suggest that the reason patients
benefit from statins is that cholesterol lowering re-
sults in shrinkage, or in slowing of progression, of
the atherosclerotic plaque and stabilisation of the
lipid rich plaque.[29,30] Thus, while the possible
role of the non-cholesterol lowering mechanisms
6. Third Report of the National
Cholesterol Education Program (NCEP III)
The NCEP III guidelines on the detection, eval-
uation and treatment of high cholesterol in adults
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Drugs 2002; 62 (12)

Who Should Receive Statins?
1713
in the management of cholesterol as a cardiovasc-
ular risk factor has been updated in light of current
data, and recently published.[32] This document
emphasises the importance of risk assessment of
all individuals, primary and secondary prevention,
LDL cholesterol lowering, and also raises the issue
of cost-effectiveness of treatment of individuals in
the various risk groups. Treatment goals for LDL
cholesterol are indicated depending on the individ-
ual’s risk category.
In secondary prevention, for those individuals
with coronary heart disease and coronary heart dis-
ease risk equivalents (much like those enrolled in
the Heart Protection Trial) the LDL cholesterol
goal is <2.60 mmol/L (100 mg/dL), those with
multiple (two or more) risk factors, the goal is
<3.36 mmol/L (130 mg/dL) and those with zero to
one risk factor, the goal is <4.15 mmol/L (<160
mg/dL). Although therapeutic lifestyle changes in
LDL cholesterol lowering therapy are indicated in
all categories, in order to achieve treatment goals,
drug therapy is often indicated, particularly in
those individuals in whom a low LDL cholesterol
level is desirable. Because of efficacy in lowering
cholesterol levels and clinical risk and high toler-
ability, the statins are generally accepted as drugs
of first choice in this regard.
In a section on primary prevention and LDL
cholesterol lowering therapy, lifestyle changes are
seen as the most cost-effective means to reduce
coronary heart disease. It is also noted that while
the ‘clinical approach to primary prevention is
founded on the public health approach that calls
for lifestyle changes, including: 1) reduced intakes
of saturated fat and cholesterol, 2) increased phys-
ical activity, and 3) weight control, to lower pop-
ulation cholesterol levels and reduce coronary
heart disease risk, … the clinical approach intensi-
fies preventive strategies for higher risk per-
sons’.[32] It is suggested that persons who are at
higher risk because of high or very high LDL cho-
lesterol levels or because of multiple risk factors
are candidates for LDL cholesterol lowering drug
therapy.[32] Such a recommendation is consistent
with the interpretation of the available data on pri-
mary prevention.
7. Translation of Trial Results
Into Practice
Despite the conclusiveness of the results from
these and other trials, available evidence indicates
that the results have not been translated into an
optimal level of practice.[33-35] There are many rea-
sons for this ‘care gap’.[33] Awareness of and will-
ingness to apply these data by the physicians, em-
powering patients to know their risk factors and to
ask for appropriate treatment, and ensuring that pa-
tients have proper access (financially) to the med-
ications are important factors. Innovative practice-
enhancing measures, which can be incorporated
seamlessly into traditional practices, may result in
closure of the ‘care gap’ and improvement in pa-
tient outcomes.[33-36] These can be simple meas-
ures such as ensuring that appropriate treatments
are started before patient discharge from hospital,
patient management clinical paths and other sys-
tematic approaches to risk factor modifications.[33,36]
8. Conclusion
Data on nearly 30 000 patients from five long-
term randomised, placebo-controlled trials of
statins have clearly demonstrated that a broad
range of individuals can benefit from such therapy.
These include men or women, younger or older
individuals, those with elevated or normal choles-
terol levels, with or without myocardial infarction
or symptomatic coronary heart disease, with or
without hypertension or diabetes, and those who
are smokers or non-smokers. Benefits include re-
ductions in the risks for myocardial infarction, cor-
onary, cardiovascular and all-cause mortality,
stroke and the need for coronary revascularisation.
Certainty of benefits is much clearer in higher risk
coronary patients than in lower risk individuals
without clinical evidence of vascular disease. Re-
sults of the recently completed Heart Protection
Trial have clearly confirmed the results of the ear-
lier trials and support the use of statin therapy in
secondary prevention. The promising role of statins
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Drugs 2002; 62 (12)

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Teo & Burton
average cholesterol levels: results of AFCAPS/TexCAPS.
JAMA 1998; 279: 1615-22
in the management of patients with acute isch-
aemic syndromes is being actively evaluated.
In primary prevention, the data are not as con-
vincing and generalisations cannot be made as to
whether, and in which subgroup, drug therapy to
lower LDL cholesterol should be initiated.
There are important cost implications and the
use of statin therapy has to be judged on an indi-
vidual basis, particularly in those with high or very
high LDL cholesterol levels and/or with multiple
risk factors placing them at high short- and long-
term risk of coronary heart disease. There is evi-
dence of a ‘care gap’ in translating trial data into
practice, even in secondary prevention, and this
‘care gap’ needs closing in order to improve patient
outcomes.
10. The Post Coronary Artery Bypass Graft Trial Investigators. The
effect of aggressive lowering of low-density lipoprotein cho-
lesterol levels and lose-dose anticoagulation on obstructive
changes in saphenous-vein coronary artery bypass grafts. N
Engl J Med 1997; 336: 153-62
11. Brown BG, Albers JJ, Fisher LD, et al. Regression of coronary
artery disease as a result of intensive lipid-lowering therapy
in men with high levels of apolipoprotein B. N Engl J Med
1990; 323: 1289-98
12. Waters D, Higginson L, Gladstone P, et al. Effects of monother-
apy with an HMG-CoA reductase inhibitor on the progression
of coronary atherosclerosis as assessed by serial quantitative
arteriography: the Canadian coronary atherosclerosis inter-
vention trial. Circulation 1994; 89: 959-68
13. MAAS Investigators. Effect of simvastatin on coronary ather-
oma: the multicentre anti-atheroma study (MAAS). Lancet
1994; 344: 633-8
14. Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin
on coronary atherosclerosis in patients with mild to moderate
cholesterol elevations (lipoprotein and coronary atherosclero-
sis study [LCAS]). Am J Cardiol 1997; 80: 278-86
15. Teo KK, Burton JR, Buller CE, et al. Long term effects of cho-
lesterol lowering and angiotensin converting enzyme inhibi-
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Acknowledgements
No funding support has been received for the production
of this article. The authors received unrestricted partial sup-
port from Merck Frosst Canada Co. for conducting a statin
trial.[15]
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