VOLUME 11 NUMBER 2 • JUNE 2014
53
SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
coronary revascularisation (
p
< 0.0001), and a 21% reduction in
stroke (
p
= 0.0002). After five years, 42 fewer diabetics per 1 000
diabetics treated with statins had major cardiovascular events.
8
In the Fenofibrate Intervention and Event Lowering in Diabetes
(FIELD) study, 9 795 type 2 diabetics (2 131 with cardiovascular
disease) were randomised to fenofibrate or double-blind placebo.
9
Mean follow up was 5.0 years. The primary outcome of coronary
events was not significantly reduced by fenofibrate. Fenofibrate
insignificantly increased coronary heart disease mortality by 19%.
9
In the Action to Control Cardiovascular Risk in Diabetes (ACCORD)
trial, 5 518 type 2 diabetics at high risk for cardiovascular disease
wererandomisedtosimvastatinplusfenofibrateortosimvastatinplus
double-blind placebo.
10
Mean follow up was 4.7 years. Compared
with simvastatin plus placebo, simvastatin plus fenofibrate did
not lower the incidence of fatal cardiovascular events, non-fatal
myocardial infarction, or non-fatal stroke.
10
Among 3 414 patients
with atherosclerotic cardiovascular disease and low serum high-
density lipoprotein (HDL) cholesterol levels treated with simvastatin
plus ezetimibe if needed to maintain the serum LDL cholesterol
less than 70 mg/dl (1.8 mmol/l), at 36-month follow up, patients
randomised to niacin had improvements in serum HDL cholesterol
and triglyceride levels but no clinical improvement compared to
patients randomised to placebo.
11
At the American College of Cardiologymeeting on 9March 2013,
Dr Jane Armitage presented results from the Heart Protection study
2 – Treatment of HDL to Reduce the Incidence of Vascular Events
(HPS2-THRIVE) study. In this study, 25 673 high-risk patients were
randomised to treatment with simvastatin or simvastatin/ezetimibe
plus extended-release niacin plus the anti-flushing agent laropri-
prant or to treatment with simvastatin or simvastatin/ezetimibe. At
the 3.9-year follow up, compared to treatment with simvastatin
or simvastatin/ezetimibe, addition of niacin did not decrease the
primary outcome of major vascular events but increased 31 serious
adverse events per 1 000 niacin-treated patients. Excess diabetic
complications were increased 3.7% (
p
< 0.0001). Excess new
diabetes was increased 1.8% (
p
< 0.0001). Excess infection was
increased 1.4% (
p
< 0.0001). Excess gastrointestinal complications
were increased 1% (
p
< 0.0001). Excess bleeding (gastrointestinal
and intracranial) was increased 0.7% (
p
< 0.0002).
The American Diabetes Association 2013 guidelines recommend
that diabetics at high risk for cardiovascular events should have their
serum LDL cholesterol reduced to less than 70 mg/dl (1.8 mmol/l)
with statins.
12
Lower-risk diabetics should have their serum
LDL cholesterol reduced to less than 100 mg/dl (2.6 mmol/l).
12
Combination therapy of a statin with either a fibrate or niacin has not
been found to provide additional cardiovascular benefit above statin
therapy alone and is not recommended.
12
Hypertriglyceridaemia
should be treated with dietary and lifestyle changes.
12
Severe
hypertriglyceridaemia should be treated with drug therapy to
decrease the risk of acute pancreatitis.
12
The 2013 American College of Cardiology/American Heart
Association lipid guidelines recommend the use of high-dose
statins (rosuvastatin 20 to 40 mg daily or atorvastatin 40 to
80 mg daily) to adults aged 75 years and younger with
atherosclerotic vascular disease (ASCVD) with or without diabetes
mellitus unless contraindicated with a class I indication.
13
Moderate-
dose or high-dose statins are reasonable to administer to patients
with ASCVD with or without diabetes mellitus older than 75 years
with a class IIa indication. Persons aged 21 years and older with a
serum LDL cholesterol of 190 mg/dl (4.9 mmol/l) or higher with or
without diabetes mellitus should be treated with high-dose statins
with a class I indication. For primary prevention in diabetics aged
40 to 75 years and a serum LDL cholesterol between 70 and
189 mg/dl (1.8 and 4.9 mmol/l), moderate-dose statins should
be given with a class I indication. For primary prevention in diabetics
aged 40 to 75 years, a serum LDL cholesterol between 70 and
189 mg/dl (1.8 and 4.9 mmol/l), and a 10-year risk of ASCVD of
7.5% or higher calculated from the Pooled Heart Equation, high-
dose statins should be administered with a class IIa indication. For
primary prevention in diabetics aged 21 to 39 years or older than 75
years and a serum LDL cholesterol between 70 and 189 mg/dl (1.8
and 4.9 mmol/l), moderate- or high-dose statins should be given
with a class IIa indication. These guidelines also state that there is
no additional ASCVD reduction from adding non-statin therapy to
further lower non-HDL cholesterol once an LDL cholesterol goal
has been reached. Clinical trials have demonstrated no lowering
of cardiovascular events or mortality in persons treated with statins
by addition of nicotinic acid, fibric acid derivatives, ezetemibe, or
drugs that raise HDL cholesterol.
13
References
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et al
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