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

Final Report Update 5 Drug Effectiveness Review Project
• Some studies found greater increases in high-density lipoprotein cholesterol with lowdose
rosuvastatin compared with atorvastatin, while other studies found no difference.
• Amongst the high potency statins, high dose of rosuvastatin increased high-density
lipoprotein cholesterol more than high dose simvastatin or atorvastatin.
• Ezetimibe-simvastatin fixed-dose combination had an equivalent effect on increasing
high-density lipoprotein cholesterol as simvastatin alone.
• Ezetimibe-simvastatin was not as effective as fenofibrate or niacin in increasing highdensity
lipoprotein cholesterol.
• Fixed-drug combination products containing extended-release niacin with lovastatin or
simvastatin were more effective in increasing high-density lipoprotein cholesterol than
simvastatin 20 mg to 40 mg, but with more adverse events.
Key Question 2a. Are there doses for each statin or fixed-dose combination
product containing a statin and another lipid-lowering drug that produce similar
percent increase in high-density lipoprotein cholesterol between statins?
Statins
A previous meta-analysis of placebo-controlled trials estimated that, on average, statins
increased high-density lipoprotein cholesterol by 3 mg/dL (0.07 mmol/l; 95% CI, 0.06 to 0.08
mmol/l), with no detectable effect of dose. 82 In our review of 77 head-to-head trials, statins
raised high-density lipoprotein cholesterol levels from 0% to 19%, with the great majority
between 5% and 9% (Evidence Table 1). While most found no significant difference in highdensity
lipoprotein cholesterol-raising among the statins, there were some exceptions.
In 6 head-to-head studies of low-density lipoprotein cholesterol lowering, simvastatin
increased high-density lipoprotein cholesterol more than atorvastatin 10 to 80 mg,
but in 14 others, there was no significant difference between the 2 on this measure.
38, 41, 52, 55, 58, 68
26, 29, 30, 39, 42, 48,
51, 53, 57, 72, 83, 84, 88, 89 In the Mulder study, the simvastatin to atorvastatin switch trial (STAT),
patients had received simvastatin 40 mg for at least 8 weeks prior to the screening visit and had
low-density lipoprotein cholesterol levels above 2.6 mmol/L (100 mg/dL) at screening. Patients
were then randomized to simvastatin 40 mg or atorvastatin 40 mg for 8 weeks, when the
atorvastatin dose was increased to 80 mg while the simvastatin dose remained the same. The
atorvastatin group had a 4.4% increase in high-density lipoprotein cholesterol whereas the
simvastatin group had a 1.8% decrease in high-density lipoprotein cholesterol, but this was not
significant. The non-equivalent dosing and patient inclusion criteria limited the utility of this
finding. There was 1 meta-analysis of randomized controlled trials of atorvastatin and
simvastatin which demonstrated that simvastatin was generally associated with greater increases
in high-density lipoprotein cholesterol than atorvastatin, with the greatest significance at the
higher doses of atorvastatin. 12
Two studies that compared atorvastatin to simvastatin were designed to measure highdensity
lipoprotein cholesterol raising as a primary outcome. 33, 59 A 24-week study of 917
patients randomized to atorvastatin 80 mg or simvastatin 80 mg reported only an average of the
increase at weeks 18 and 24, separately, by baseline high-density lipoprotein cholesterol level. 33
The average increase was the same in patients with baseline high-density lipoprotein cholesterol
above and below 40 mg/dL: 2.1% for patients randomized to atorvastatin and 5.4% for those
randomized to simvastatin. These differences were not statistically significant. In the other study
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