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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 5, September/October 2020
AFRICA
249
The patients with LDL-C
>
5.0 mmol/l were younger than those
who reached their LDL-C goal (mean age 53.9
±
10.9 vs 62.9
±
10.5 years). These patients had in general been on treatment for
longer periods of time [14.3 (11.6) vs10.9 (7.4) years] and the
majority (81.3%) had been diagnosed with FH (Table 6). Only
four patients with LDL-C
>
5.0 mmol/l were receiving maximal
lipid treatment. Very low LDL-C (
<
1.0 mmol/l) level was
uncommon and was only seen in 13.7% of patients.
Using the rosuvastatin and ezetimibe equivalent dose
adjustments, most patients received the equivalent of 20 mg
rosuvastatin (30.8%) followed by the 40 mg equivalent dose
(27.4%) (Table 7).
Modelling analysis
Model 1: This model estimated the impact of up-titrating
all patients who were not receiving ezetimibe to a maximal
statin dose. We included all patients not at goal, who were
not on ezetimibe and who were not receiving a rosuvastatin
dose equivalent of 40 mg in this simulation. For each patient
we calculated how many doublings they were away from the
rosuvastatin 40-mg dose equivalent. For example, a patient
who was on rosuvastatin 20 mg was one doubling away from
rosuvastatin 40 mg, a patient on atorvastatin 20 mg (equivalent
to rosuvastatin 10 mg) was two doublings away. The number
of doublings was calculated by dividing 40 by the current dose
equivalent and then deriving the log base 2. We then multiplied
the result for the number of doublings required by 6% and
subtracted this percentage from the current LDL-C level.
For example, a patient on atorvastatin 5 mg with an LDL-C
of 3.5 mmol/l would be receiving a rosuvastatin dose equivalent
of 2.5 mg. This patient would be four doublings (40/2.5
=
16
and log
2
16
=
4) away from a rosuvastatin dose equivalent of 40
mg. Maximising the statin dose in this patient would result in
an additional 24% (4
×
6%) reduction in LDL-C level and the
estimated LDL-C level on maximal statin therapy would be 2.66
mmol/l.
Maximising the statin dose in the 171 patients eligible for this
intervention would result in an additional 31 (18.1%) patients
reaching LDL-C goal.
Model 2: This model estimated the impact of maximising the
statin dose (if required) and then adding ezetimibe. We included
all patients not at target who were not receiving ezetimibe,
irrespective of statin dose in this analysis. In a first step we
maximised the statin dose as shown above (for those who needed
it) and then estimated the effect of ezetimibe by lowering the
LDL-C level by a further 18%.
We included 265 patients in this analysis. This strategy would
allow 92 (34.7%) additional patients to reach their LDL-C goal.
Model 3: With this model we evaluated the impact of maximising
the statin dose, adding ezetimibe and then a PCSK9 inhibitor. In
the first step we estimated the effect of increasing the statin dose
to the maximum and adding ezetimibe to all patients who were
not taking ezetimibe. We assumed that PCSK9 inhibitors would
reduce the LDL-C level by a further 60% and calculated at-target
rates following addition of a PCSK9 inhibitor.
Using this strategy, most patients not at goal (310 of 322,
96.3%) were able to reach their LDL-C target.
Model 4: In our last model we included all patients not at target
and estimated the impact of adding a PCSK9 inhibitor without
changing any of the other lipid-lowering therapy. With this
intervention 92.9% (299 of 322 patients) would be at LDL-C
goal.
Discussion
As CARDIO TRACK targeted a very high-risk population,
the very high prevalence of diabetes mellitus (64.4%) and
hypertension (77.6%) were not surprising. A significant number
of patients (16.3%) were still smoking despite their very high-risk
status.
The majority of the study population did not reach their
LDL-C goal of
<
1.8 mmol/l despite treatment with maximum-
tolerated doses of high-intensity statins. The reasons for this are
likely multifactorial.
Assuming that high-intensity statins reduce LDL-C level
approximately 50% from baseline, then many patients with an
untreated LDL-C
>
3.6 mmol/l are not likely to reach target on
a statin alone. Poor adherence to lipid-lowering therapy is also
common and although we attempted to exclude patients with a
history of non-adherence, we did not objectively assess adherence
in this study. In a recent analysis of patients with probable FH
in the ICPLS study, the real-world observed LDL-C reductions
from baseline were also significantly lower than those projected
based on reported statin potency.
14
In an observational study of patient records from a German
claims database, Kostev and colleagues reported that only 15%
of 49 406 very high-risk patients with dyslipidaemia achieved a
target LDL-C level of
<
1.8 mmol/l despite high-dose statin use
and a medication dispensing rate above 80%.
15
Furthermore,
this study was based in Germany, making generalisability to a
heterogeneous South African population challenging.
Ezetimibe was underused in our study population. Multiple
other trials conducted in very high-risk populations also show
a low use of statin plus ezetimibe combination therapy. In the
FOURIER trial that evaluated the addition of evolocumab to
conventional lipid-lowering therapy in patients with established
atherosclerotic cardiovascular disease, only 5% of the study
population were on ezetimibe treatment at enrollment.
16
Similarly, in the alirocumab ODYSSEY OUTCOME trial, only
3% of patients with an acute coronary syndrome within the last
year were on ezetimibe.
17
Table 7. Rosuvastatin dose equivalent based on statin potency
±
ezetimibe use and LDL-C goal attainment
*
Rosuvastatin dose
equivalents (mg)
(n
=
468
*)
n
(% of study population)
Reached LDL-C goal (
n
=
146)
n
(% on dose at goal)
2.5
4 (0.8)
2 (50)
5
27 (5.8)
12 (44)
10
105 (22.4)
39 (37)
20
144 (30.8)
55 (38)
40
128 (27.4)
29 (23)
80
7 (1.5)
2 (29)
160
6 (1.3)
2 (33)
320
47 (10.0)
5 (11)
*The effect of adding ezetimibe to a statin was estimated by doubling the rosu-
vastatin dose equivalent three times – patients taking rosuvastatin 40 mg/d and
ezetimibe are therefore estimated to be taking a rosuvastatin dose equivalent of
320 mg/d.