EURO PEAN
SO CIETY O F
CARDIOLOGY ®
Original scientific paper
LDL cholesterol goals and cardiovascular
risk during statin treatment: the IDEAL
study
European Journal of Cardiovascular
Prevention & Rehabilitation
0(00) 1–8
! The European Society of
Cardiology 2011
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DOI: 10.1177/1741826710389391
ejcpr.sagepub.com
Anders G Olsson1, Christina Lindahl2, Ingar Holme3,
Rana Fayyad4, Ole Faergeman5, John JP Kastelein6, Matti
J Tikkanen7, Mogens Lytken Larsen5 and Terje R Pedersen3
(on behalf of the Incremental Decrease in End Points Through
Aggressive Lipid Lowering Study Group)
Abstract
Aims: We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who
achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End
Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how lipoprotein components related to cardiovascular disease (CVD) outcomes in these groups.
Methods and results: For subjects who reached on-treatment LDL-C goals, Cox regression models were used to
assess the ability of lipoprotein components to predict CVD events. Treatment with simvastatin or atorvastatin resulted
in 40 per cent and 80 per cent of patients, respectively, reaching the 2.5 mmol/l goal and 12 per cent and 52 per cent,
respectively, reaching the 2.0 mmol/l goal, after 1 year (all p < 0.001 between groups). Adjusting for baseline LDL-C
levels, hazard ratio (HR) for those reaching 2.0–2.5 mmol/l LDL-C versus those reaching <2.0 mmol/l was 1.16
(95% confidence interval [CI], 1.02–1.33, p ¼ 0.023). An increase of the apolipoprotein B/A1 (apoB/A1) ratio by 1
standard deviation in participants who reached 2.0 mmol/l showed a HR for CVD of 1.14 (95% CI, 1.04–1.25, p ¼ 0.004).
Conclusion: More CVD patients treated with atorvastatin than simvastatin achieved either LDL-C goal and those
reaching the 2.0 mmol/l goal exhibited significantly less CVD than those only reaching 2.5 mmol/l. In those reaching the
2.0 mmol/l goal, the apoB/A1 ratio still bears a relation to CVD outcome. The use of apoB/A1 ratio may provide
additional predictive value to that of LDL-C.
Keywords
Apolipoprotein, atorvastatin, coronary heart disease, lipoproteins, prevention, simvastatin
Received 10 May 2010; accepted 25 July 2010
Introduction
Recent guidelines for prevention of cardiovascular disease
(CVD) have formulated goals for low-density lipoprotein
cholesterol (LDL-C) in patients with and without overt
disease. For patients with CVD, the Joint European
Guidelines1 recommend an upper LDL-C level of
2.5 mmol/L with an option of 2.0 mmol/L, if feasible.
The corresponding recommendation in the National
Cholesterol Education programme – Adult Treatment
Panel III2 is <100 mg/dL (2.6 mmol/l,) or preferably
<70 mg/dl (1.8 mmol/l). The Incremental Decrease in
End Points Through Aggressive Lipid Lowering
1
Department of Internal Medicine, University Hospital, Linköping, and
Stockholm Heart Center, Sweden.
2
Pfizer Sweden, Sollentuna, Sweden.
3
Center of Preventive Medicine, Oslo University Hospital, Ullevål, Oslo,
Norway.
4
Pfizer Inc, New York, New York, USA.
5
Department of Medicine-Cardiology A, Århus University Hospital,
Århus, Denmark.
6
Academic Hospital Amsterdam, Amsterdam, The Netherlands.
7
Medical Clinic, Helsinki University Hospital, and the Folkhälsan Research
Center, Helsinki, Finland.
Corresponding author:
Anders G Olsson, Bergviksvägen 48, SE-167 63 Bromma, Sweden
Email: [email protected].
Downloaded from cpr.sagepub.com at PENNSYLVANIA STATE UNIV on May 18, 2016
2
European Journal of Cardiovascular Prevention & Rehabilitation 0(00)
(IDEAL) study primarily tested the hypothesis of whether
intensive lowering of LDL-C with high-dose atorvastatin
(80 mg) would prevent recurrent coronary outcomes more
efficiently than a moderate dose (20–40 mg) of simvastatin. The latter was already shown to be effective in coronary patients in the 4S3 and Heart Protection studies4.
In this post-hoc analysis of the IDEAL study we set out to
assess to what extent patients in the different treatment
arms were able to achieve the goals formulated in the recommendations. We also wanted to explore how different
lipoprotein components (LCs) were related to outcome in
those who reached the formulated LDL-C goals of 2.5 or
2.0 mmol/l. As several studies5,6 have indicated that the
apolipoprotein B/apolipoprotein A1 (apoB/A1) ratio is
a better risk predictor than LDL-C, we also studied the
relationship between these LCs and formulated corresponding goals for apoB/A1.
Patients and methods
The design and methodology of the IDEAL trial7 have
been described earlier. In brief, we used a prospective,
randomized, open-label, blinded-endpoint evaluation
(PROBE) design and randomized 8888 patients with a
history of confirmed acute myocardial infarction (MI)
to approximately 5 years of treatment with either atorvastatin 80 mg daily or simvastatin 20 or 40 mg daily.
Randomization was 1 : 1 to atorvastatin or simvastatin,
and there was no wash-out or run-in period. Patients
were seen at 12 and 24 weeks and every 6 months thereafter. The simvastatin dose could be increased from
20 mg to 40 mg daily if the plasma C concentration at
24 weeks was 5.0 mmol/l. Except for such cases,
plasma lipid concentrations were not revealed to
study personnel during the study. Overall adherence
to study drugs was 89 per cent in the atorvastatin
group and 95 per cent in the simvastatin group. For
the current analysis we used the average concentrations
of lipoprotein lipids and apolipoproteins measured at
12 and 24 weeks to avoid the influence of measurement
errors inherent in studies in which single values are used
for prediction purposes. LDL-C was calculated by the
Friedewald formula, and apoB and apoA1 were measured by turbidimetric methods with calibration to the
World Health Organization International Federation
of Clinical Chemistry primary standard (WHOIFCC). In this prospective subgroup analysis of the
IDEAL population, we included only patients who
had survived to the 6-month visit without any cardiovascular event start and with complete 12- and 24-week
values of LDL-C, non–high-density lipoproteincholesterol (HDL-C), apoB and apoA1.
The time to first occurrence of major coronary events
– the primary endpoint – was non-significantly lower in
the atorvastatin group (hazard ratio (HR) 0.89 (95%
confidence interval (CI), 0.78–1.01, p ¼ 0.07)8. The corresponding figure for the endpoint used in the present
study – any cardiovascular event, i.e. time to first occurrence of coronary death, non-fatal MI, cardiac arrest
with resuscitation, stroke, coronary revascularization,
hospitalization for unstable angina or congestive heart
failure and peripheral arterial disease – was HR 0.84
(95% CI, 0.78–0.91, p < 0.001).
Statistical methods
The proportion of subjects who reached LDL-C goals
of <2.0 mmol/l and <2.5 mmol/l at baseline, Year 1,
and at the final visit were computed. In addition, for
subjects who reached on-study LDL-C goals of
<2.0 mmol/l and <2.5 mmol/l, Cox regression models
were used to assess the ability of the LC mean of apoB,
apoB/apoA1, LDL-C, and non–HDL-C at Months
3 and 6, to predict any cardiovascular event. This was
done first by comparing 2nd quartiles, 3rd quartiles and
4th quartiles (vs 1st quartiles) of the LCs. Tests for
trend were also conducted by assigning an ordinal
score to each quartile. The effect on any cardiovascular
event of a 1 standard deviation (SD) increase was also
assessed for each LC. In addition, HRs to assess the
risk of LDL-C >2.5 mmol/l versus LDL-C <2.0 mmol/l
and
LDL-C 2.5–2.0 mmol/l
versus
LDL-C
<2.0 mmol/l on any cardiovascular event were computed. Adjustments were made for age, sex, smoking,
hypertension, diabetes, systolic blood pressure, baseline
LDL-C, congestive heart failure and previous statin
treatment.
Results
The baseline characteristics of the IDEAL participants
reaching the 2.5 and 2.0 mmol/l goals at Year 1 are
given in Table 1. All participants in the IDEAL study
had survived a MI. Mean age was approximately
62 years and >80 per cent of the participants were
males. No significant differences in baseline characteristics were found between those reaching 2.5 mmol/l
versus the 2.0 mmol/l goal. Baseline LDL-C was only
0.11 mmol/l higher in those participants reaching the
2.5 mmol/l LDL-C goal than in those reaching the
2.0 mmol/l goal.
The proportions of participants in the IDEAL study
reaching the LDL-C goal at the time points of 1 year
and final visit are presented in Table 2. For the goal of
2.5 mmol/l, 21.8 per cent of the participants (identical
between those allocated to atorvastatin or simvastatin)
were already at goal at the baseline visit. The corresponding figures for the LDL-C goal of 2.0 mmol/l
were 5.3 per cent and 5.4 per cent for those subsequently allocated to atorvastatin and simvastatin,
Downloaded from cpr.sagepub.com at PENNSYLVANIA STATE UNIV on May 18, 2016
Olsson et al.
3
Table 1. Baseline characteristics of patients reaching the 2.5
and 2.0 mmol/l goal at Year 1 in the IDEAL study
Goal
2.5 mmol/l
2.0 mmol/l
Number of patients
Age (years; mean SD)
Sex (% male)
Smoking (%)
Hypertension (%)
Systolic blood pressure
(mmHg; mean SD)
Diabetes (%)
Congestive heart failure (%)
Previous statin treatment (%)
LDL-Ca (mmol/l)
Triglycerides (mmol/l)
HDL-Cb (mmol/l)
Apolipoprotein B (g/l)
Apolipoprotein A1(g/l)
Apolipoprotein B/A1
Non–HDL-C (mmol/l)
5023
62.1 9.3
81.9
18.9
33.3
137.0 19.9
2668
62.3 9.4
82.9
18.9
33.2
136.4 19.8
13.2
6.2
75.7
2.92 0.82
1.64 0.86
1.18 0.31
1.13 0.30
1.39 0.23
0.83 0.27
3.65 0.92
14.1
6.4
73.4
2.81 0.81
1.64 0.89
1.17 0.32
1.09 0.29
1.38 0.22
0.81 0.26
3.53 0.92
a
LDL-C: low-density lipoprotein cholesterol; bHDL-C: high-density lipoprotein cholesterol.
Table 2. Numbers and percentages of patients attaining goals of
<2.5 and 2.0 mmol/l by year and type of treatment
Visit
Goal (mmol/l) Atorvastatin
Simvastatin
p-value
Baseline
Year 1
Final visit
Baseline
Year 1
Final visit
<2.5
<2.5
<2.5
<2.0
<2.0
<2.0
954 (21.8%)
1700 (40.2%)
1864 (42.9%)
237 (5.4%)
486 (11.5%)
650 (15.0%)
0.954
<0.0001
<0.0001
0.860
<0.0001
<0.0001
951 (21.8%)
3323 (79.6%)
3213 (74.1%)
232 (5. 3%)
2182 (52.3%)
2048 (47.2%)
respectively. At Year 1, the 2.5 mmol/l goal was reached
in four of five patients on atorvastatin (80 mg) and in
approximately two of five patients on simvastatin (20 or
40 mg). At the final visit this goal was reached by
slightly fewer patients on atorvastatin while this
proportion was about the same as after 1 year in the
simvastatin-treated group. The corresponding proportions of the 2.0 mmol/l goal attainers at Year 1 were
approximately 50 per cent in those on atorvastatin and
slightly more than 10 per cent on simvastatin.
The mean LDL-C, apoB, and non–HDL-C concentrations and apoB/A1 ratio of those IDEAL participants who reached the 2.5 and 2.0 mmol/l goals are
presented in Table 3. The mean baseline apoB/A1
ratio was 0.65 for those reaching the LDL-C goal of
2.5 mmol/l versus 0.58 for those reaching the 2.0 mmol/l
goal. For atorvastatin subjects who reached the LDL-C
goal of 2.5 mmol/l at the end of the study, the mean
reduction in apoB/A1 ratio was 0.29 versus 0.19 for
those on simvastatin. The reduction from baseline in
apoB/A1 ratio was highly significant for both groups
(p < 0.001) and the difference between the treatment
groups in change in apoB/A1 was also statistically
significant (p < 0.0001). The corresponding mean reductions of apoB/A1 ratios for those reaching the LDL-C
goal of 2.0 mmol/l were 0.30 and 0.22 for those treated
with atorvastatin and simvastatin, respectively. The
reductions from baseline and the difference in reduction
between these treatment groups were also highly significant (p < 0.0001). For subjects who reached LDL-C
goals of 2.5 and 2.0 mmol/l at the final visit, all the
lipids and lipoproteins were statistically significantly
different between treatments (p < 0.001) (Table 3).
The HRs and their 95% CIs for subjects reaching the
LDL-C goals of <2.0 mmol/l, 2.0–2.5 mmol/l and
>2.5 mmol/l in the two treatment groups are presented
in Table 4. The HR for those who reached the LDL-C
goal of <2.00 mmol/l was set to 1.0. Adjustments were
made for baseline LDL-Cs. In both treatment groups,
Table 3. Lipoprotein variables in statin-treated subjects reaching the LDL-C goals of 2.5 and 2.0 mmol/l in the IDEAL study
LDL-C goal
Baseline
<2.5 mmol/l Year 1
Final visit
LDL-C goal
Baseline
< 2.0 mmol/l Year 1
Final visit
LDL-Ca (mmol/l)
Apolipoprotein B (g/l)
Apolipoprotein B:A1
Non–HDL-C
b
Atorvac
Simvad
Atorva
Simva
Atorva
Simva
Atorva
Simva
2.10 0.28
1.78 0.37
1.79 0.37
1.70 0.20
1.56 0.27
1.56 0.26
2.10 0.28
2.07 0.29
2.03 0.31
1.70 0.20
1.69 0.21
1.68 0.21
0.86 0.15
0.74 0.17
0.77 0.16
0.75 0.14
0.67 0.14
0.70 0.13
0.85 0.15
0.87 0.17
0.87 0.15
0.74 0.14
0.74 0.16
0.77 0.15
0.65 0.17
0.55 0.15
0.56 0.15
0.58 0.16
0.51 0.14
0.52 0.14
0.65 0.17
0.63 0.17
0.62 0.16
0.58 0.18
0.55 0.16
0.57 0.17
2.80 0.41
2.33 0.46
2.36 0.47
2.45 0.41
2.11 0.38
2.13 0.38
2.78 0.42
2.74 0.46
2.69 0.44
2.42 0.41
2.35 0.41
2.38 0.42
a
LDL-C: low-density lipoprotein cholesterol; bHDL-C: high-density lipoprotein cholesterol; cAtorvastatin; dSimvastatin.
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(mmol/l)
4
European Journal of Cardiovascular Prevention & Rehabilitation 0(00)
Table 4. Hazard ratios and their 95% CIs for subjects reaching the LDL-C goals of <2.0 mmol/l, 2.0–2.5 mmol/l, and >2.5 mmol/l in
the atorvastatin and simvastatin treatment groups. Adjustments were made for baseline LDL-C
LDL-Ca range (mmol/l)
Atorvastatin
<2.0
2.0–2.5
2.5
HRb
1.0
1.14
1.29
Simvastatin
95% CIc
p
0.96–1.36
1.04–1.60
0.13
0.02
HR
1.0
1.03
1.02
Overall
95% CI
p
HR
95% CI
p
0.80–1.33
0.79–1.31
0.82
0.90
1.16
1.28
1.02–1.33
1.12–1.46
0.023
<0.001
a
LDL-C: low-density lipoprotein cholesterol; bHR: hazard ratio; cCI: confidence interval.
the HR for any cardiovascular event increased by
increasing LDL-C levels. For atorvastatin-treated
subjects, the HR ratio increased significantly for those
individuals who reached 2.5 mmol/l compared with
those who obtained the 2.0 mmol/l goal. Thus, the
lower the LDL-C levels the IDEAL participants
reached, regardless of whether the treatment was with
atorvastatin or simvastatin, the lower was the risk of a
cardiovascular event. This trend was more robust for
atorvastatin but was particularly noted when the two
treatment groups were pooled. In the overall group it is
clear that the HR is also significantly higher between
those with LDL-C of 2.0–2.5 mmol/l and those with
LDL-C of <2.0 mmol/l. Treatment by LDL-C category
interactions were not significant (p > 0.25), indicating a
consistent effect of LDL-C category on risk for both
treatments.
The relation of apoB, apoB/A1, LDL-C and
non–HDL-C to any cardiovascular event in participants reaching the goals of 2.5 mmol/l and 2.0 mmol/l
are presented in Table 5. For those participants reaching the LDL-C goal of 2.5 mmol/l, all lipoprotein
variables – apoB, apoB/A1, LDL-C and non–HDL-C
– showed significantly higher cardiovascular risk in the
4th compared with the 1st quartile of the distribution.
Also, the increase in cardiovascular risk by an increase
of 1 SD of the risk variable showed the same: the higher
the level of the risk variable, the higher the risk for a
cardiovascular event. For those participants reaching
the LDL-C goal of 2.0 mmol/l, only apoB/A1 showed
a significant difference between the 1st and 4th quartiles
and with 1 SD increase.
The relationships between LDL-C and apoB, apoB/
A1 and non–HDL-C are presented in Figures 1 to 3.
For the highly significant relationship between LDL-C
and apoB, it can be seen that LDL-C concentrations of
2.5 and 2.0 mmol/l correspond to apoB levels of 98 and
81 mg/dl, respectively. For non–HDL-C, the corresponding figures are 3.1 and 2.6 mmol/l. For the
apoB/A1 ratio, 2.5 mmol/l of LDL-C corresponds to
0.73 for males and 0.67 for females. The ratios for
LDL-C of 2.0 mmol/l were 0.61 and 0.56 for males
and females, respectively. The slopes of the male and
female regression lines for the relationship between
apoB/A1 ratio and LDL-C differed significantly
(p < 0.001), indicating that men increased their apoB/
A1 ratio more per increase in LDL-C than women.
Discussion
Current European and American guidelines for CVD
prevention recommend a LDL-C goal for patients with
elevated CVD risk of <2.5 mmol/l and <2.6 mmol/l
(100 mg/dl), respectively, with optional goals of <2.0
and <1.8 mmol/l (70 mg/dl)1,2. In this post-hoc analysis
of the IDEAL study we demonstrated that CHD
patients prescribed atorvastatin (80 mg per day) reach
the 2.5 mmol/l and 2.0 mmol/l goals in approximately
80 per cent and 50 per cent of cases, respectively. The
corresponding figures for simvastatin 20 and 40 mg are
approximately 40 per cent and 10–15 per cent, respectively. Thus, half of this high-risk population could
achieve the toughest goal with a single tablet of a
potent statin. Along with others, we have previously
demonstrated that this regimen is well tolerated in a
majority of patients8–11.
Even if the participants in the IDEAL study were
not randomized to the LDL-C targets of 2.0 and
2.5 mmol/l, our results point to the notion that treating
coronary heart disease (CHD) patients to a target of
2.0 mmol/l significantly improves their prognosis for
future events compared with those only reaching the
goal of 2.5 mmol/l (Table 4). While the results for atorvastatin reach significance between those achieving the
2.0 mmol/l goal versus those not achieving the
2.5 mmol/l goal, the results for simvastatin are
weaker. In Europe, simvastatin is the statin that is
most frequently prescribed to CHD patients. Based
on our results, this suggests suboptimal statin treatment
in secondary prevention today.
In a recent study in patients hospitalized with CHD,
mean LDL-C was 2.7 mmol/l with almost half of the
admission LDL-C levels being below the treatment
target of 2.6 mmol/l12. Approximately 20 per cent of
the participants took cholesterol-lowering medication.
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ApoB: apolipoprotein B; bLDL-C: low-density lipoprotein cholesterol; cHDL-C: high-density lipoprotein cholesterol; dHR: hazard ratios; eCI: confidence interval. Trend p-values for 4th vs 1st quartiles of
apoB, apoB/A1, LDL-C and non-HDLC, respectively, were: <0.0001, 0.0002, 0.006 and 0.0011 for the <2.5 mmol/l goal and 0.075, 0.005, 0.253 and 0.107 for the <2.0 mmol/l goal.
a
0.97–1.17
1.06
0.196
0.199
0.285
0.361
0.085
0.604
0.035
0.550
0.108
0.470
0.009
0.188
0.075
0.098
0.004
0.005
p-value
0.97–1.17
1.06
1.14
1.08
1.28
1.19
1.43
1.11
1.25
1.08
1.34
1.07
1.27
1.13
1.16
0.52–0.89 0.89–1.52 0.87–1.47 0.97–1.65 0.83–1.37 1.02–1.75 0.83–1.42 0.95–1.64 0.84–1.46 1.10–1.87 0.92–1.55 0.98–1.67 0.99–1.19 1.04–1.25
95% CI
_2.0 mmol/l
HR
0.68
1.11
1.10
1.031.18 1.04–1.19
0.004
0.001
1.16
1.13
1.34
1.28
1.38
1.46
1.15
1.11
1.20
1.28
1.06
1.03
1.04
_2.5 mmol/l
HRd
1.23
ApoB/ A1 LDL-C
ApoB
ApoBa
ApoB/A1
LDL-Cb
Non–
HDL-Cc
ApoB
ApoB/A1
LDL-C
Non–
HDL-C
ApoB
ApoB/A1
LDL-C
Non–
HDL-C
Increase of 1 SD in the variable
4th vs 1st quartiles
3rd vs 1st quartiles
2nd vs 1st quartiles
Table 5. Relation between lipid risk variables and any cardiovascular events in subjects reaching LDL-C <2.5 mmol/l and <2.0 mmol/l in the IDEAL study
95% CIe 1.02–1.48 0.86–1.25 0.86–1.25 0.88–1.28 1.07–1.55 1.00–1.44 0.92–1.33 0.96–1.38 1.22–1.75 1.15–1.66 1.07–1.53 1.12–1.61 1.06–1.21 1.12–1.27
p-value 0.031
0.690
0.726
0.512
0.009
0.055
0.268
0.142
<0.0001 0.0006
0.008
0.0016
0.0002
<0.0001
5
Non–
HDL-C
Olsson et al.
The authors concluded that the results provided further
support for recent guideline revisions using a tougher
LDL-C goal of 2.0 mmol/l. In the present IDEAL
cohort, the vast majority of patients were being treated
with a statin at baseline.
Our data recently gained further support from the
Treating to New Targets (TNT)13 study in which intensive lipid lowering to a mean LDL-C level of 2.1 mmol/l
with atorvastatin 80 mg/day in patients with previous
percutaneous coronary intervention reduced major cardiovascular events by an additional 21 per cent and
repeat revascularizations by 27 per cent compared
with a less intensive lipid-lowering regimen.
In a recently published joint subgroup analysis of the
combined IDEAL and TNT patient cohorts, the total/
HDL-C and the apoB/A1 ratios in particular were each
more closely associated with outcome than any of the
individual proatherogenic LCs. We therefore previously concluded that in patients receiving statin therapy, on-treatment levels of non–HDL-C and apoB were
more closely associated with cardiovascular outcome
than levels of LDL-C. Inclusion of measurements of
the antiatherogenic lipoprotein fraction further
strengthened these relationships14.
The present study extends the results from our
previous subgroup analysis of the IDEAL study
where we conclude that apolipoproteins and ratios of
apolipoproteins are better predictors for future cardiovascular outcome than LDL-C15. In the present analysis we also show that even in CHD patients reaching the
toughest LDL-C goal, the ratio apoB/A1 still carries a
significant risk. This indicates that even lower risk may
be obtained by further decreasing LDL-C <2.0 mmol/l
or increasing apoA1 containing lipoproteins by specific
HDL-raising drugs such as niacin16 or inhibitors of
cholesterol ester transfer such as dalcetrapib17. These
data support the use of non–HDL-C, apoB, or apoB/
A1 ratio as novel treatment targets for statin therapy.
We suggest that the conventional treatment goal of
LDL-C at 2.5 mmol/l could be substituted with an
apoB/A1 ratio of 0.73 for males and 0.67 for females.
The corresponding figures for the goal of LDL-C of
2.0 mmol/l could be 0.61 and 0.56 for males and
females, respectively.
The above conclusion has been recently underpinned
by data analysis from the Measuring Effective
Reductions in Cholesterol Using Rosuvastatin therapy
(MERCURY) II trial by Ballantyne et al.18 The LDLC target of 2.6 mmol/l corresponds to an apoB level of
90 mg/dl19. However, during statin therapy, to reach an
apoB target of 90 mg/dl it was necessary to reduce
LDL-C to 1.8 mmol/l. This is because statin treatment
affects the cholesterol component more in LDL than
the apoB component. In this paper we have demonstrated that CVD risk is reduced in subjects who
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European Journal of Cardiovascular Prevention & Rehabilitation 0(00)
Scatter data
3
ApoB =0.98 g/L
2
ApoB (g/L)
ApoB =0.81 g/L
1
y =0.35 x + 0.11,P<0.0001,r2= 0.81
0
0
1
2
3
4
LDL-C
5
6
7
8
Figure 1. Relationship between LDL-C and apoB in patients on statin treatment in the IDEAL study.
10
Non-HDL-C
= 3.14 mmol/L
Non HDL-C (mmol/L)
8
Non-HDL-C
= 2.59 mmol/L
6
4
2
y =1.90 x+ 0.415,P<0.0001,r2= 0.89
0
0
1
2
3
4
LDL-C
5
6
7
8
Figure 2. Relationship between LDL-C and non–HDL-C in patients on statin treatment in the IDEAL study.
attain LDL-C levels <2.0 mmol/l versus those who only
attain LDL-C levels <2.5 mmol/l. Furthermore, in
those who attain the lower LDL-C goal, apoB/A1 is
still a significant predictor of risk. We and others20
have demonstrated the importance of apoB/A1 ratio
as a CVD predictor and this strengthens the case for
sharpening the LDL-C goal <2.5 mmol/l.
Study limitations
This analysis of the IDEAL data set is a subgroup analysis with the inherent uncertainties of this type of data
handling. To address the questions asked in this work it
would have been more appropriate to aim at the two
goals of 2.0 and 2.5 mmol/l as surrogate endpoints
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Olsson et al.
7
3
ApoB/ApoA1
2
1
0
0
1
2
3
4
LDL-C
5
6
7
8
Figure 3. Relationship between LDL-C and apoB/apoA1 in patients on statin treatment in the IDEAL study.
instead of two types of statin treatments. We have
adjusted for baseline LDL-C in this subgroup analysis
but cannot exclude the possibility that other unidentified biases may occur. Also, it cannot be excluded that
the two statins used may have exerted differential
effects on LCs. In particular, it is well known that simvastatin tends to increase HDL-C and apoA1 to a
greater extent than atorvastatin. However, as the
present results are in line with current concepts we
have no reason to believe our results have been
skewed in any significant way.
Conclusion
We conclude from this subgroup analysis of the
IDEAL study that CHD patients reaching the new
LDL-C goal of 2.0 mmol/l fare significantly better in
their cardiovascular risk than those reaching the
2.5 mmol/l target. It is possible to reach the tougher
goal in 50 per cent of the cases with atorvastatin
80 mg daily. In those patients achieving target
LDL-C, further cardiovascular benefits may be seen
in those patients with lower levels of other surrogate
markers, such as non–HDL-C or apoB/A1 ratio.
Funding
This study was sponsored by Pfizer Inc. Graphical support and assistance with formatting of the manuscript
was provided by Paul Lane, PhD, of UBC Scientific
Solutions Ltd and funded by Pfizer Inc.
These data have been presented in part in poster format
at the European Society of Cardiology Congress, 2009,
Barcelona, Spain.
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