Atorvastatin is metabolised by cytochromes P‐450 3A4 and P‐450 3A5 to ortho‐hydroxy atorvastatin and para‐hydroxy atorvastatin. The lipid‐lowering effect of atorvastatin is not influenced by the time of day the drug is administered, probably because of its relatively long half‐life of 20 hours. Atorvastatin is rapidly absorbed, reaching peak plasma concentration within 2.3 hours. Atorvastatin and the five other available statins are prescribed to prevent adverse cardiovascular events and to lower blood total cholesterol and LDL‐cholesterol. Review authors were unable to assess harms of atorvastatin because the included trials were too short, and because only 34 included trials assessed harms.Ītorvastatin is the statin most widely prescribed in the world ( IMS 2012). Risk of bias for all assessed trials was high. Atorvastatin works similarly to rosuvastatin in lowering cholesterol but is about three‐fold less potent. The effect was greater with higher doses than with lower doses. Atorvastatin showed a consistent effect in lowering blood cholesterol over the dose range of 2.5 to 80 mg daily.
PILL LOOK UP L277 UPDATE
This update found 42 additional trials and reports on 296 trials in 38,817 participants. We searched for all evidence obtained from three‐ to 12‐week trials reporting the effect of atorvastatin on blood cholesterol. It is therefore important to know the magnitude of the effect that atorvastatin has on cholesterol.
It is an HMG‐CoA reductase inhibitor that is prescribed to prevent adverse cardiovascular events and to lower blood total cholesterol and LDL‐cholesterol. Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. This represents the first update of this review, which was published in 2012 (Adams 2012). Withdrawals due to adverse effects were not statistically significantly different between atorvastatin and placebo groups in these short‐term trials (risk ratio 0.98, 95% confidence interval 0.68 to 1.40). Risk of bias for the outcome of withdrawals due to adverse effects (WDAEs) was high, but the mostly unclear risk of bias was judged unlikely to affect lipid measurements. Subgroup analyses suggested that the atorvastatin effect was greater in females than in males and was greater in non‐familial than in familial hypercholesterolaemia.
The slope of dose‐related effects on cholesterol and LDL‐cholesterol was similar for atorvastatin and rosuvastatin, but rosuvastatin is about three‐fold more potent. Over this range, blood LDL‐cholesterol is decreased by 37.1% to 51.7% (Summary of findings table 1). The Summary of findings table 1 documents the effect of atorvastatin on LDL‐cholesterol over the dose range of 10 to 80 mg/d, which is the range for which this systematic review acquired the greatest quantity of data.
PILL LOOK UP L277 TRIAL
Log dose‐response data from both trial designs revealed linear dose‐related effects on blood total cholesterol, LDL‐cholesterol, HDL‐cholesterol and triglycerides. Included are 242 before‐and‐after trials and 54 placebo‐controlled RCTs. The update consists of 296 trials that evaluated dose‐related efficacy of atorvastatin in 38,817 participants. In this update, we found an additional 42 trials and added them to the original 254 studies.
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