2008 Clinical Practice Guidelines - Canadian Diabetes Association

mally controlled with a statin), niacin (immediate-release
or extended-release formulation) is the adjuvant agent of
choice. Combination lipid-lowering therapy with niacin is
generally safe (32-35). Niacin can cause deterioration of
glycemic control (32) (although there is now evidence that
the adverse effects of niacin on glycemia may have been
overemphasized [33]).
In the placebo-controlled HDL Atherosclerosis Treatment
Study (HATS) (34), combined low-dose simvastatin (10 to
20 mg/day) and high-dose niacin (2 to 4 g/day) stabilized
coronary atherosclerosis with an associated ≥13% absolute
risk reduction (up to 90% relative risk reduction) for CV
outcomes, although the number of subjects with diabetes
was small. In the Arterial Biology for the Investigation of the
Treatment Effects of Reducing Cholesterol (ARBITER) 2
trial, 1 g extended-release niacin added to existing statin
therapy significantly improved HDL-C (21%),TG and non-
HDL-C, and likely contributed to observed reduction of
carotid intima-media thickness in subjects also treated with
a statin (35).
Specific targets for TG are not provided in these guidelines
because there are very few clinical trial data to support
recommendations based on specific TG target levels.
Nonetheless, aTG level of 10.0 mmol/L
who do not respond to other measures such as tight glycemic
control, weight loss and restriction of refined carbohydrates
and alcohol. For those with moderate hyper-TG (4.5 to
10.0 mmol/L), either a statin or a fibrate can be attempted
as first-line therapy, with the addition of a second lipid-lowering
agent of a different class if target lipid levels are not
achieved after 4 to 6 months on monotherapy.While several
studies have shown that CVD prevention is associated with
fibrate treatment (38-42), there is much less evidence for
CVD risk reduction with fibrates relative to statins in people
with diabetes. In some studies, no statistically significant
reduction in the primary endpoint was demonstrated with
fibrate therapy (43,44). Combination therapy with fenofibrate
(45,46) or bezafibrate plus a statin appears to be relatively
safe if appropriate precautions are taken (Tables 2A and
2B), but the efficacy of these approaches with regard to outcomes
has yet to be established. Because of an increased risk
of myopathy and rhabdomyolysis, statins should not be used
in combination with gemfibrozil (47).
Although monotherapy with niacin or fibrates has been
shown to prevent CVD events, there is currently insufficient
evidence for statin plus niacin and no evidence for fibrate plus
niacin combinations to reduce CV risk in people with diabetes.
However, adequately powered, event-reduction, prospective,
randomized, controlled clinical trials are currently underway
with various classes of agents to examine whether the addition
of other therapies in individuals already treated with statins
further reduces CV events and/or prolongs survival (Action
to Control Cardiovascular Risk in Diabetes [ACCORD] for
statin plus fibrate; Atherothrombosis Intervention in
Metabolic Syndrome with Low HDL-C/High Triglyceride and
Impact on Global Health Outcomes [AIM HIGH] for statin
plus extended-release niacin). Until the results of these clinical
trials become available, for high-risk individuals who have
a persistent elevation of TC/HDL-C despite achieving the primary
LDL-C target of ≤2.0 mmol/L, niacin or fibrates can be
added to statin therapy at the physician’s discretion.
ADDITIONAL LIPID MARKERS OF CVD RISK
Apo B, Apo B/Apo A1 ratio
There is 1 apolipoprotein B molecule (apo B) per LDL, very
low-density lipoprotein and intermediate-density lipoprotein
particle (all of which are atherogenic).Apo B has repeatedly
been shown to be a better risk marker for CVD events
than LDL-C; consequently, the measurement of apo B and its
monitoring in response to lipid-lowering therapy has been
advocated by some (48).The measurement of apo B is most
clinically useful in the individual with hyper-TG, since it provides
an indication of the total number of atherogenic
lipoprotein particles in the circulation. In such cases, knowledge
of the apo B level may guide the aggressiveness with
which lipid-lowering therapy is pursued (i.e. more aggressive
therapy in individuals in whom the apo B level is elevated).An
optimal level of apo B in high-risk individuals has not
yet been precisely determined, but based on available evidence
can be considered to be ~