Lipid lowering efficacy of atorvastatin

Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids.

To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE).

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied.

Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks.

Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials.

Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45).

Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.