Luck is a fickle mistress. Some people are so lucky it
defies all logic —you know, those folks you've uninvited
to poker night because you're sick of their smug smiles
when they inevitably clean you out. Then there are those
poor blighters who just can't seem to catch a break. There's
at least one in every crowd who seems to have permanently
fallen out of favour with lady luck. When it comes to
patients with hypercholesterolemia on lipid-lowering meds,
there are actually six out of 100 in every crowd who respond
to statin therapy with an unexpected drop in high-density
lipoprotein-cholesterol (HDL-C) levels. This nasty surprise
increases their ratios of total cholesterol (TC) to HDL-C
and LDL-C to HDL-C levels, and their risk of cardiovascular
events.
However, Dr Dirk Devroey and colleagues
at the University of Brussels noticed that some of their
so-called 'bad HDL-C responder' patients weren't always
in such a bad way: their HDL-C levels were almost twice
as high when taking a fibrate, as compared with statin
treatment. So there may still be a chance that everything
will even out in the end for these unfortunate folk.
The researchers combed their records
from 1991-2000 to find patients treated with statin
and fibrate monotherapy for hyper-cholesterolemia and
whose HDL-C levels had dropped below 40mg/dl during
statin treatment. For their study, published in the
May 25 issue of International Journal of Cardiology,
the doctors whittled 120 prospects down to 14 patients
who'd been on both monotherapies at different times.
DARE
TO COMPARE
Records showed that for an average of 1.2 years of fibrate
monotherapy, eight patients received fenofibrate 200mg,
the rest received either ciprofibrate or bezafibrate.
Nine patients received pravastatin, and the others either
simvastatin or fluvastatin for a mean of 1.1 years of
monotherapy. In the end, the researchers were able to
confirm their suspicions, noting, "when switching the
bad HDL-C responders from statins to fibrates, HDL-C
increases significantly with more favorable TC to HDL-C
and LDL to HDL-C ratios." All patients had higher HDL-C
levels during fibrate treatment — an average of
49% higher compared with statins therapy — 11 of
the 14 had HDL-C levels above 40mg/dl. TC to HDL-C and
LDL-C to HDL-C ratios were respectively 26% and 27%
lower with fibrates. As an added bonus, triglyceride
(TG) levels were 24% lower with fibrates too.
For bad responders, "the switch
from fibrates to statins is justifiable for patients
with low or normal LDL-C. For patients with high LDL-C,
it might be better to add fibrates to the statins,"
suggest the authors. Past studies have also shown that
increasing HDL-C with fibrates reduces the risk of major
cardiovascular events in patients with coronary heart
disease.
SAFETY
FIRST
"Unfortunately, since a relatively high incidence of
undesirable adverse effects between statins and gemfibrozil
has been reported, physicians are reluctant to prescribe
statins combined with fibric acid", says Dr Kwang Kon
Koh, Director of the Vascular Medicine and Atherosclerosis
Unit at Gachon Medical School in Incheon, Korea. But
one fibric acid derivative, fenofibrate, does not appear
to induce severe myopathy - either alone or in combination.
To illustrate the positive effects
of fenofibrate, Dr Koh and his colleagues from the National
Institutes of Health compared patients' vascular and
metabolic responses to each drug, alone or in combination,
in a study published May 17 in the Journal of the American
College of Cardiology.
MIX
WITH CONFIDENCE
The 56 patients enrolled in the trial all had combined
hyperlipidemia, defined as TC over 200mg/dl and TG ranging
from 200-800mg/dl. The patients were given 10mg atorvastatin
and placebo, atorvastatin and 200mg fenofibrate, or
fenofibrate and placebo daily during each two-month
treatment period of the crossover trial.
Combining fenofibrate with statin
therapy produced significantly greater effects on insulin
sensitivity and several measures of endothelial function
than atorvastatin therapy alone. What's more, no patients
dropped out due to serious adverse events. "Statins
combined with fenofibrate did work effectively with
safety in these patients," confirms Dr Koh.
Int J Cardiol May 25, 2005;101(2):
231-5
J Am Coll Cardiol May 17, 2005;45(10):1649-53
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