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Dean L. PubMed Clinical Q&A [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2008-2013.

PubMed Clinical Q&A [Internet].

Comparing Statins and Combination Drugs

Laura Dean, MD.

Created: November 1, 2010.

An important risk factor for coronary heart disease (CHD) is a raised cholesterol level, in particular, a high level of the "bad cholesterol" known as LDL-c. In patients who require drug therapy to lower their level of LDL-c, statins are the first-line agents.

Statins work by blocking the enzyme HMG-CoA reductase, the rate-limiting step in the manufacture of cholesterol. There are currently 6 statins available in the US, and a further 3 combination drugs that combine a statin with either extended-release niacin (vitamin B3, thought to improve lipid levels in several ways) or ezetimibe (inhibits the absorption of cholesterol from the gut).

The "Drug Class Review on HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin" compares the safety and effectiveness of nine drugs. A summary of the findings is below.

How do statins and combination drugs compare in lowering "bad" cholesterol (LDL-c)?

All statins can reduce LDL-c by up to 35%.

The following statins and combination products can reduce LDL-c by up to 50%:

The combination product ezetimibe-simvastatin is superior to a statin alone in reducing LDL-c. [full review]

The following statins and combination drugs can reduce LDL-c by more than 50%:

The combination product ezetimibe-simvastatin is more likely to reduce LDL-c levels by more than 50% than any statin alone.

In studies directly comparing statins at the highest doses, atorvastatin (80 mg) lowered LDL-c more than simvastatin (80 mg) but resulted in more adverse events, while rosuvastatin (40 mg) was superior to atorvastatin (80 mg) in reducing LDL-c levels and resulted in a similar frequency of adverse events. [full review]

How do statins and combination drugs compare in increasing "good cholesterol" (HDL-c)?

For statins, in general, doses that have similar effects on lowering LDL-c also have similar effects on increasing HDL-c. Some studies found that simvastatin and rosuvastatin were superior to atorvastatin in increasing HDL-c, while other studies found no difference. [full review]

Among combination products, ezetimibe-simvastatin had a similar effect to simvastatin alone on increasing HDL-c, and was not as effective as fenofibrate or niacin. While combination products containing extended-release niacin with lovastatin or simvastatin were more effective in increasing HDL-c than simvastatin alone, they were associated with more adverse events. [full review]

How do statins and combination drugs compare in reducing the risk of coronary events, stroke, or death?

Evidence from direct comparisons is limited, and there are no data for combination products. But comparisons with placebo have shown:

In patients without coronary heart disease:

In patients at high risk for cardiovascular events:

In patients with coronary heart disease:

How do statins and combination drugs compare in safety and harms?

All statins can increase creatine kinase, an enzyme found in muscle, but the risk of symptomatic muscle disease such as myalgia, myopathy and rhabdomyolysis, remains low.

All statins can also increase liver enzymes (transaminases), but there is no evidence that this increases the risk of liver failure. Studies have found that atorvastatin (80 mg) has a higher rate of increase in liver transaminases than pravastatin (40 mg) or simvastatin (80 mg).

For combination products containing a statin and niacin, there are higher rates of adverse events leading to discontinuation compared to a statin alone, mainly because of flushing. [full review]

How do statins and combination drugs compare in children?

In general, the children in studies had an inherited lipid disorder. In one head-to-head trial in children, atorvastatin 80 mg and rosuvastatin 80 mg lowered LDL-C by a similar amount, but neither drug improved HDL-c levels. Compared to placebo, several statins were found to improve LDL-c levels, and combined results showed a small improvement (3%) in HDL-c.

A single trial found the combination product ezetimibe-simvastatin was superior to a statin alone in reducing LDL-c. [full review]

Evidence about adverse events in children is limited, but several studies reported that significant increases in creatinine kinase and liver enzymes were infrequent. If they did occur, levels improved without needing to stop the medication. [full review]

Does gender, age, or ethnicity influence the safety and effectiveness of statins and combination drugs?

There is good evidence that women and the elderly benefit from statin therapy. Less evidence exists for different ethnic groups, and for the comparative safety of statins and combination drugs in these groups.

One study found rosuvastatin was linked with a 2-fold higher blood level of the drug in Asians (having either Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian origin), compared with Caucasians taking the same dose. [full review]

Statins included in this review

Generic NameTrade Names
AtorvastatinLipitor
FluvastatinLescol
Lescol XL
LovastatinMevacor
Altoprev extended release
PravastatinPravachol
RosuvastatinCrestor
SimvastatinZocor

Combination products included in this review

Generic NameTrade Names
Ezetimibe-SimvastatinVytorin
Lovastatin-Niacin-ERAdvicor
Simvastatin-Niacin-ERSimcor

Further information

Image th-statins09.jpgThis PubMed Clinical Q&A was reviewed by Susan Carson, MPH.

For the full report and evidence tables, please see:
Smith MEB, Lee NJ, Haney E, et al. Drug Class Review: HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin: Final Report Update 5 [Internet]. Portland (OR): Oregon Health & Science University; 2009 Nov. Available at: http://www.ncbi.nlm.nih.gov/books/NBK47273/.