DOC News July 1, 2004
Volume 1 Number 1 p. 5
© 2004 American Diabetes Association
Combining Fibrates and Statins to Lower Cardiovascular Risk
Anne Peters Harmel, MD
Question: "Is it safe and appropriate to use fibrates with
statins?"
Answer: It is very important to reduce the risk of cardiovascular
disease in patients with diabetes. Increasing data show the importance of
lowering LDL cholesterol levels in patients with type 2 diabetes with statin
therapy. In the recently released data from the CARDS trial, it was shown that
10 mg of atorvastatin reduced the risk of cardiovascular events, even in
patients with a baseline LDL cholesterol level of less than 100 mg/dL.
Therefore, statin therapy is considered first-line for CVD risk reduction in
patients with diabetes.
However, diabetic dyslipidemia is multifactorial. Frequently, no elevation
in LDL cholesterol is found—in fact, an increase in serum triglycerides
and a decrease in HDL levels are the common lipid abnormalities found. And
although most patients with type 2 diabetes benefit from use of an LDL
cholesterol–lowering agent, triglyceride levels often remain elevated.
What we don't know is whether further therapy to lower triglyceride levels
will add to the risk reduction seen with statin therapy. We have some evidence
that lowering triglyceride levels with fibrates is beneficial, but we await
definitive evidence on the benefits of combined therapy. In the multicenter
NIH-funded ACCORD trial, patients in the lipid-lowering arm of the trial are
being randomized to receive either simvastatin 20 mg alone or simvastatin plus
fenofibrate. This study should provide definitive data as to the benefits of
combination statin plus fibrate therapy. Until these data are available, we
need to use the evidence we already have to make therapeutic decisions.
Triglyceride lowering will occur as blood glucose levels are brought into
the normal range. Some glucose-lowering drugs, such as pioglitazone, will
lower triglyceride levels more than other agents. Certain statins, such as
atorvastatin and rosuvastatin, may also provide more triglyceride lowering
than other agents. However, in spite of this, triglyceride levels may remain
above the target of 150 mg/dL. In this case, using combined statin plus
fibrate therapy should be considered. The risk of this combination is that of
rhabdomyolysis, or muscle breakdown. This can be quite serious and lead to
kidney failure and death. At my institution we had several such cases when
cerivastatin (a drug no longer on the market) was combined with gemfibrozil.
However, the statins that remain on the market do not cause this reaction
nearly as frequently. Moreover, the risk of the reaction can be reduced by
using fenofibrate instead of gemfibrozil and giving lower doses of the statin
drug when using a combination (for instance, 20 mg of simvastatin instead of
40 mg).
The combination of a fibric acid derivative plus a lower-dose statin may
provide additional cardiovascular disease risk reduction compared with statin
therapy alone, in patients who have continued elevations in triglyceride
levels. These patients should be monitored for side effects, such as
elevations in liver function tests and CPK level, and should be counseled to
call if they develop unexplained muscle pain.
Additionally, agents that could increase circulating statin levels, such as
macrolide antibiotics or grape-fruit, should be avoided. Finally, following a
healthy diet and exercising regularly, maintaining blood glucose levels in the
normal range (glycated hemoglobin [A1C] levels as close to 6% as possible),
and using daily aspirin therapy as well as ACE inhibitors and
angiotensin-receptor blockers are all important components of lowering CVD
risk in patients with type 2 diabetes.
Footnotes
Do you have a clinical question? Send your query to
docnews{at}diabetes.org
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Dr. Harmel is director of the University of Southern California Westside
Center for Diabetes.
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