(Statins) and Fixed-dose Combination Products Containing a Statin

Final Report Update 5 Drug Effectiveness Review Project
the trials studied the fixed-dose combination of ezetimibe and simvastatin (Vytorin). Of these, 7
compared ezetimibe-simvastatin to another statin, 1 compared ezetimibe-simvastatin to niacin,
and 1 to fenofibrate. Of the trials comparing ezetimibe-simvastatin to another statin, there were
no differences between ezetimibe-simvastatin 10/10-10/80 mg and simvastatin 10-80 mg.
102, 104
There were 2 randomized open-label trials that compared ezetimibe-simvastatin to doubling the
current statin dose. One study used the 10/20 mg dose of ezetimibe-simvastatin and the other
used the 10/40 mg dose. In the lower dose trial, doubling the statin involved increasing
simvastatin to 40 mg or atorvastatin to 20 mg, which effectively increased high-density
lipoprotein cholesterol significantly greater than switching to ezetimibe-simvastatin 10/20 mg. 106
In the second trial, patients were on multiple different statin therapies at the onset of the trial and
there was no difference between doubling the current statin dose and switching to ezetimibesimvastatin
10/40 mg. 105 There were 2 trials that compared ezetimibe-simvastatin to atorvastatin.
Both reported greater increases in high-density lipoprotein cholesterol with ezetimibesimvastatin.
100, 101 Two trials compared ezetimibe-simvastatin 10/20 mg to other lipid-lowering
drugs. In 1 trial the comparator was fenofibrate 160 mg and in the other trial the comparator was
extended-release niacin titrated to 2000 mg per day. In both of these trials, ezetimibe-simvastatin
increased high-density lipoprotein cholesterol by 8.1% to 9.3%, however the comparator had a
greater effect, an increase of 18.2% for fenofibrate and 28.1% for extended-release niacin.
108, 116
Three trials evaluated extended-release niacin fixed-dose combination products and all
reported a greater ability to increase high-density lipoprotein cholesterol than a statin. 110-112 The
SEACOAST trial was a randomized double-blind active-control trial comparing niacin extended
release-simvastatin 1000/20 mg and 2000/20 mg to simvastatin 20 mg. The fixed-dose
combination increased high-density lipoprotein cholesterol by 18.3% and 24.9% respectively,
however 35.9% of those in the higher-dose niacin extended release-simvastatin group had an
adverse event and 15.6% discontinued treatment because of an adverse event compared with
17.5% and 5.3% respectively in the simvastatin group. Of note, patients in the simvastatin group
did receive 50 mg of immediate-release niacin with their study medication, and the niacin
extended release-simvastatin group was titrated on a 4- to 12-week period. 110
Key Question 2b. Is there a difference in the ability of a statin or fixed-dose
combination product containing a statin and another lipid-lowering drug to
achieve National Cholesterol Education Panel goals?
There were no differences between the fixed-dose combinations of ezetimibe and simvastatin
and statin monotherapy in achieving National Cholesterol Education Program high-density
lipoprotein goals. 100, 101, 103-107 In the SEACOAST I randomized double-blind active-control trial
comparing the fixed-dose combination of extended-release niacin and simvastatin to simvastatin
monotherapy, a significantly higher percentage of patients met the National Cholesterol
Education Program Adult Treatment Panel III high-density lipoprotein cholesterol goal when
taking extended-release niacin-simvastatin 2000/20 mg than when taking simvastatin 20 mg. 110
Statins Page 34 of 128