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SA JOURNAL OF DIABETES & VASCULAR DISEASE
DRUG TRENDS
VOLUME 8 NUMBER 2 • JUNE 2011
91
Fenofibrate benefits in cardiovascular risk reduction:
Heartwire
discussion endorses use in type 2 diabetes
A
recent discussion on
Heartwire
following
data released on fenofibrate usage in the
United States and Canada highlights 25 years
of clinical experience and the proven benefit of
fenofibrate when used with a statin to reduce
cardiovascular risk, particularly in patients with
a high triglyceride concentration (
>
2 mmol/l)
The importance of the reduced morbid-
ity from cardiovascular events, the reduction
in retinopathy, and the reduced incidence of
rhabdomyolylsis are powerful motivators for
usage in high-risk diabetic patients, according
to participating clinicians.
1
The value of fenofibrate in reducing the
risk of pancreatitis is also worthy of clinical
emphasis, while concern about raised creatine
levels should not be overemphasised. Raised
alanine amino transferase (ALT) levels, which
may occur relate to stimulation of the ALT gene
and not to liver damage, according to a clinical
pharmacologist participating in the discussion.
2
In South Africa, a health economist
reviewed the cost saving of fenofibrate treat-
ment for middle-aged individuals with type 2
diabetes and showed a cost saving of 18%
due to the reduction in myocardial infarction,
stroke and the need for angiography or revas-
cularisation in type 2 diabetes patients.
3
The author concluded that fenofibrate
(Lipanthyl) resulted in a cost saving due to the
prevention of cardiovascular events, includ-
ing myocardial infarction and stroke, when it
was used in the treatment of type 2 diabet-
ics as in the FIELD study. It should therefore
be considered to be cost effective, even when
just the cardiovascular risk-reduction effect is
considered. The addition of fenofibrate should
be favourably considered for inclusion in the
management regimes for type 2 diabetes.
This study was based on the FIELD study,
as the ACCORD results were released after the
completion of this cost–benefit analysis (Table
1).
4
When the ACCORD data were included in
a recently published meta-analysis of published
clinical trials conducted over the past 50 years,
the analysis confirmed the value of fibrates to
a broad range of high-risk patients.
5
The cardiovascular event reduction was
highest in patients with a higher mean base-
line triglyceride concentration (
>
2 mmol/l), a
finding that agrees with subgroup analyses
done in several clinical trials, including the
ACCORD trial.
6
No increased effect was seen
in the subgroup of patients defined by a lower
HDL cholesterol level in this meta-analysis. The
ACCORD trial had placed patients with raised
triglyceride and low HDL cholesterol levels in
a subset, which showed greatest proportional
risk reduction, such that only 20 individuals
needed to be treated for five years to prevent
one cardiovascular event.
Data from the ACCORD trial available in
published form to the authors of the meta-
analysis did not allow the low-HDL subgroup
to be separated from the high-triglyceride
subgroup. So currently, the role of fibrates in
reducing cardiovascular events in a subgroup
of patients with low HDL levels and triglycer-
ides below 2 mmol/l should be the subject of
further investigation.
This extensive meta-analysis included
45 000 individuals with a broad range of
baseline characteristics. With regard to other
cardiovascular conditions, the risk of heart
failure was reported in three trials of 8 581
participants who had 584 heart-failure events.
Overall, there was no benefit of fibrates on
heart failure. However, when the VA CO-OP
atherosclerosis trial,
7
which included patients
with pre-existing cerebrovascular disease,
was excluded from the meta-analysis, fibrates
showed an 18% reduction in heart failure.
Three trials including more than 15 000
patients showed that fibrates reduced the
risk of albuminuria by 14%. A very significant
reduction of 37% was seen in the relative risk
of diabetic retinopathy in two trials, which
included more than 10 000 patients.
8,9
J Aalbers, Special Assignments Editor
1.
Freeman WE Jr. Statin-fibrate combination therapy.
Am J Cardiol
2008;
101
(10): 1521.
2.
http:www. The heart.org/article/1200719-viewed
on 3/29/2011.
3.
Wessels F. Is fenofibrate a cost-saving treatment for
middle-aged individuals with type 2 diabetes? A
South African private-sector perspective.
Cardiovasc
J Afr
2010;
21
: 43–46
4.
FIELD study supports the value of fenofibrate in
type 2 diabetes management – World Diabetes
Congress, Cape Town, 2007.
5.
Jun M, Foote C, Lu J,
et al
. Effects of fibrates on
cardiovascular outcomes: a systematic review
and meta-analysis.
Lancet
. DOI 10:1016/50140-
6736(10)60656-3. Published online May 11, 2010.
6.
Ginsberg HN, Elam MB, Lovato LC,
et al
. for the
ACCORD study group. Effects of combination lipid
therapy in type 2 diabetes mellitus.
N Engl J Med
2010;
362
: 1563–1574.
7.
The Veterans Administration Cooperative study
group. The treatment of cerebrovascular disease
with clofibrate. Final report of the Veterans
Aministration cooperative study of atherosclerosis.
Neurology Section.
Stroke
1973;
4
: 684–693.
8.
Emmerich KH, Paritis N, Stelmane I,
et al
. Efficacy
and safety of etofibrate in patients with non-
proliferative diabetic retinopa-thy.
Klin Monastbl
Augenheilkd
2009;
226
: 561–567.
9.
Keech AC, Mitchell P, Summanen PA,
et al
., for the
FIELD study investigators. Effect of fenofibrate on
the need for laser treatment for diabetic retinopathy
(FIELD study): a randomised controlled trial.
Lancet
2007;
370
: 1687–1697.
Table 1.
Key outcomes from FiELD
Endpoint
No (%) of patients
Fenofibrate
n
=
4 895
Placebo
n
=
4 900
Relative risk
(%)
p
-value
Components of primary outcome:
Non-fatal MI
158 (3)
207 (4)
–24
0.01
CHD death
110 (2)
93 (2)
19
0.22
Secondary outcomes:
Total CVD events
612 (13)
683 (14)
–11
0.035
CVD mortality
140 (3)
127 (3)
11
0.41
Total mortality
356 (7)
323 (7)
11
0.18
Total stroke
158 (3)
175 (4)
–10
0.36
Coronary revascularisation
290 (6)
364 (7)
–21
0.003
All revascularisation
380 (8)
471 (10)
–20
0.001
Only first event for each patient counted in each row
