52
VOLUME 11 NUMBER 2 • JUNE 2014
RESEARCH ARTICLE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Wilbert S Aronow
Cardiology Division, New York Medical College
Valhalla, NY, USA.
Tel: (914) 493-5311; Fax: (914)-235-6274
e-mail:
Originally published in
Int J Diabetol Vasc Dis Res
2014;
2
: 301
S Afr J Diabetes Vasc Dis
2014;
11
(2): 52–53
Treatment of hypercholesterolaemia in patients with
diabetes mellitus
Wilbert S Aronow
Abstract
Numerous studies have shown that statins reduce
cardiovascular events, including stroke and mortality in
diabetics. The American Diabetes Association 2013 guidelines
recommend that diabetics at high risk for cardiovascular
events should have their serum low-density lipoprotein
(LDL) cholesterol reduced to < 70 mg/dl (1.8 mmol/l) with
statins. Lower-risk diabetics should have their serum LDL
cholesterol reduced to < 100 mg/dl (2.6 mmol/l). The 2013
American College of Cardiology/American Heart Association
lipid guidelines recommend giving high-dose statins to adult
diabetics aged ≤ 75 yearswith atherosclerotic vascular disease
(ASCVD) unless contraindicated with a class I indication and
moderate-dose or high-dose statins to diabetics with ASCVD
≥ 75 years with a class IIa indication. Diabetics ≥ 21 years with
a serum LDL cholesterol of ≥ 190 mg/dl (4.9 mmol/l) should
be treated with high-dose statins with a class I indication.
For primary prevention in diabetics aged 40 to 75 years and
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% calculated from the Pooled Heart Equation, high-
dose statins should be given 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
189mg/dl (1.8 and 4.9mmol/l), moderate-dose statins or high-
dose statins should be given with a class IIa indication. There
is no additional ASCVD reduction from adding non-statin
therapy to further lower non-high-density lipoprotein (HDL)
cholesterol once an LDL cholesterol goal has been reached.
Clinical trials have found no lowering of cardiovascular
events or mortality in diabetics treated with statins with the
addition of nicotinic acid, fibric acid derivatives, ezetemibe,
or drugs that raise serum HDL cholesterol.
Introduction
Numerous studies have demonstrated that statins reduce
cardiovascular events, including stroke and mortality in
diabetics.
1,8
A five-year follow up of 5 963 diabetics aged 40 to 80 years in
the Heart Protection Study randomised to simvastatin 40 mg
daily or to double-blind placebo, simvastatin reduced first major
vascular event (coronary event, stroke or revascularisation) 22%
from 25.1% to 20.2% compared with placebo (
p
< 0.0001).
1
Of
the 2 912 diabetics without occlusive arterial disease at study
entry, simvastatin reduced first major vascular event by 33%
(
p
= 0.0003).
1
Of the 2 426 diabetics with a serum low-density
lipoprotein LDL cholesterol level below 116 mg/dl (3 mmol/l) at
study entry, simvastatin reduced first major vascular event by 27%
(
p
= 0.0007).
1
Treatment of diabetics without occlusive arterial
disease for five years reduced one major vascular event in 45
patients per 1 000 treated, and prevented 70 first or subsequent
major vascular events per 1 000 patients treated.
1
At 5.4-yearmedian followupof 202diabeticswith coronary artery
disease and hypercholesterolaemia in the Scandinavian Sim-vastatin
Survival study, compared with double-blind placebo, dia-betics
randomised to simvastatin 20 to 40 mg daily had a 43% reduction
in all-cause mortality (
p
= 0.087), a 55% reduction in major coronary
events (
p
= 0.002), and a 37% reduction in any atherosclerotic
event (
p
= 0.018).
2
At the five-year follow up of 586 diabetics
with coronary artery diseases and a mean serum total cholesterol
level of 209 mg/dl (5.4 mmol/l) in the Cholesterol and Recurrent
Events trial, compared with double-blind placebo, pravastatin
40 mg daily decreased the incidence of fatal coronary events or non-
fatal myocardial infarction 25% from 37% to 29% (
p
= 0.05).
3
In the Collaborative Atorvastatin Diabetes Study, 2 838 diabetics
with no cardiovascular disease and a serum LDL cholesterol less than
160 mg/dl (4.1 mmol/l) were randomised to atorvastatin 10 mg
daily or to double-blind placebo.
4
At the 3.9-year median follow up,
compared with placebo, atorvastatin significantly reduced time to
first occurrence of acute coronary events, coronary revascularisation
or stroke by 37% (
p
= 0.001), acute coronary events by 36% (9 to
55%), stroke by 48% (11 to 69%), and all-cause mortality by 27%
(
p
= 0.059).
4
In an observational prospective study of 171 men and 358
women, mean age 79 years, with prior myocardial infarction, diabetes
mellitus, and a serum LDL cholesterol of 125 mg/dl (3.24 mmol/l) or
higher, 279 of 529 diabetics (53%) were treated with statins.
5
At the
29-month follow up, compared with no treatment with statins, use
of statins significantly decreased in elderly persons, coronary heart
disease death or non-fatal myocardial infarction by 37% and stroke
by 47%.
5
The greater the reduction in serum LDL cholesterol, the
greater the reduction in new coronary events
6
and in stroke.
7
A meta-analysis was performed of 14 randomised trials of statins
used to treat 18 686 diabetics (1 466 with type 1 diabetes and
17 220 with type 2 diabetes).
8
Mean follow up was 4.3 years. All-
cause mortality was reduced 9% per mmol/l reduction in serum
LDL cholesterol (
p
= 0.02). Major cardiovascular events were
reduced 21% per mmol/l reduction in serum LDL cholesterol,
p
<
0.0001. Statins caused in diabetics a 22% reduction in myocardial
infarction or coronary death (
p
< 0.0001), a 25% reduction in
