Evidence-base - International Diabetes Federation

Global Guideline for Type 2 Diabetes
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The guidelines also address the issue of management of serum triglyceride
and HDL cholesterol levels, an area where the evidence-base is softer, but
all conclude that management with fibrates is indicated if serum triglyceride
levels are raised and HDL cholesterol is low. However, there is no consensus
on the levels at which fibrates should be introduced, or on how they should be
introduced in combination with statins.
Fibrates significantly reduce non-fatal MI but have no significant effect on CVD
or all-cause mortality, fatal MI or stroke, all of which are significantly reduced
by statins. Jun et al found overall benefit of fibrates in preventing major CVD
events primarily due to a reduction in coronary disease with no effect on
stroke, CVD or all-cause mortality [19] . A meta-analysis specific to people with
diabetes also found a significant reduction in non-fatal coronary events but no
effect on stroke or mortality outcomes [20] . Interestingly fibrates significantly
reduced retinopathy and amputations [21,22] . In general, fibrates are safe and
easy to use and fenofibrate can be co-administered with a statin [23] . The
benefit of combination therapy is not clear with the ACCORD study reporting
no benefit of adding fibrates to statins, rather than statin therapy alone,
to reduce cardiovascular risk in people with type 2 diabetes at high-risk of
CVD [24] . It should be noted that co-administration of statins with gemfibrozil is
not recommended due to the increased risk of myopathy.
The evidence-base for other lipid-lowering medications (extended-acting
nicotinic acid, concentrated omega-3 fatty acids, ezetimibe, bile acid binding
resins) is weaker and there are very few quality outcomes studies [6] . The use
of these agents is generally reserved for uncontrolled hyperlipidaemia when
taking first-line agents, or intolerance of these.
For people with established CVD the benefit of long-term aspirin for reducing
the risk of MI, stroke and vascular death is well established [25,26] . However
guidelines generally do not support the routine use of aspirin (or other antiplatetet
agents) in CVD prevention in people who have not had a CVD event [4,6,8] .
Evidence from three meta-analyses [26-28] indicates that aspirin does not affect
all-cause or CVD-related mortality, but does have a small benefit in reducing
non-fatal vascular events (e.g., MI or stroke), a benefit driven largely by a
reduction in non-fatal MI among men. Aspirin increases the relative risk for
gastrointestinal and extracranial bleeds by 54%. Based on the absolute benefits
and risks observed the Calvin et al analysis [29] , aspirin therapy for an average
of 6.4 years prevents approximately three CVD events per 1,000 women and
results in 2.5 major bleeding events and in 1,000 men aspirin prevents four
cardiovascular events and results in three major bleeding events. The findings
of four systematic reviews [26,28-30] are consistent and report that the effects of
aspirin therapy in people with diabetes are smaller than those for the general
population, which has lead to a conservative approach about aspirin therapy for
CVD prevention in people with diabetes.
Dual anti-platelet therapy is also not recommended for primary prevention
of CVD. The CHARISMA study examined the efficacy and safety of dual antiplatelet
therapy with clopidogrel and aspirin versus aspirin alone. In the primary
prevention cohort (2,289 of the 15,603 participants), cardiovascular death was
non-significantly increased with dual therapy (single 1.8% versus dual 3.0%,
p=0.07) [31] .