Rosuvastatin for lowering lipids Edited (no change to conclusions)
Rosuvastatin is one of the most potent statins and is currently widely prescribed. It is therefore important to know the dose‐related magnitude of effect of rosuvastatin on blood lipids.Objectives
To quantify the effects of various doses of rosuvastatin on serum total cholesterol, low‐density lipoprotein (LDL)‐cholesterol, high‐density lipoprotein (HDL)‐cholesterol, non‐HDL‐cholesterol and triglycerides in participants with and without evidence of cardiovascular disease.
To quantify the variability of the effect of various doses of rosuvastatin.
To quantify withdrawals due to adverse effects (WDAEs) in the randomized placebo‐controlled trials.Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 10 of 12, 2014 in The Cochrane Library, MEDLINE (1946 to October week 5 2014), EMBASE (1980 to 2014 week 44), Web of Science Core Collection (1970 to 5 November 2014) and BIOSIS Citation Index (1969 to 31 October 2014). No language restrictions were applied.Selection criteria
Randomized controlled and uncontrolled before‐and‐after trials evaluating the dose response of different fixed doses of rosuvastatin on blood lipids over a duration of three to 12 weeks.Data collection and analysis
Two review authors independently assessed eligibility criteria for studies to be included and extracted data. WDAEs information was collected from the placebo‐controlled trials.Main results
One‐hundred and eight trials (18 placebo‐controlled and 90 before‐and‐after) evaluated the dose‐related efficacy of rosuvastatin in 19,596 participants. Rosuvastatin 10 to 40 mg/day caused LDL‐cholesterol decreases of 46% to 55%, when all the trials were combined using the generic inverse variance method. The quality of evidence for these effects is high. Log dose‐response data over doses of 1 to 80 mg, revealed strong linear dose‐related effects on blood total cholesterol, LDL‐cholesterol and non‐HDL‐cholesterol. When compared to atorvastatin, rosuvastatin was about three‐fold more potent at reducing LDL‐cholesterol. There was no dose‐related effect of rosuvastatin on blood HDL‐cholesterol, but overall, rosuvastatin increased HDL by 7%. There is a high risk of bias for the trials in this review, which would affect WDAEs, but unlikely to affect the lipid measurements. WDAEs were not statistically different between rosuvastatin and placebo in 10 of 18 of these short‐term trials (risk ratio 0.84; 95% confidence interval 0.48 to 1.47).Authors' conclusions
The total blood total cholesterol, LDL‐cholesterol and non‐HDL‐cholesterol‐lowering effect of rosuvastatin was linearly dependent on dose. Rosuvastatin log dose‐response data were linear over the commonly prescribed dose range. Based on an informal comparison with atorvastatin, this represents a three‐fold greater potency. This review did not provide a good estimate of the incidence of harms associated with rosuvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 44% of the placebo‐controlled trials.
Stephen P Adams, Sarpreet S Sekhon, James M Wright
Plain language summary
The effect of rosuvastatin on cholesterol
Rosuvastatin (Crestor) is one of the most potent statins and is currently widely prescribed. It is therefore important to know how much rosuvastatin lowers cholesterol. We searched for all the trial evidence from trials of three to 12 week duration reporting the effect of rosuvastatin on cholesterol. We found 108 trials involving 19,596 participants. Based on an informal comparison with atorvastatin three‐fold lower doses of rosuvastatin are needed to lower cholesterol by the same amount. This review cannot be used to assess harms of rosuvastatin, because of the short duration of these trials and the high risk of bias for this outcome; adverse effects were only reported in 10 of the 18 trials that could be used to assess harms.
Stephen P Adams, Sarpreet S Sekhon, James M Wright
Implications for practice Specific findings of the review
1. Rosuvastatin 1 to 80 mg/day causes a linear dose‐response reduction in the per cent change from control of blood total cholesterol, LDL‐cholesterol, non‐HDL‐cholesterol and triglycerides, but not for HDL‐cholesterol. Manufacturer‐recommended rosuvastatin doses of 10 to 40 mg/day resulted in 45.8% to 54.6% decreases of LDL‐cholesterol. From the slope of the lines there was a 3.7%, 4.4%, and 4.2% decrease in blood total cholesterol, LDL‐cholesterol, and non‐HDL‐cholesterol, respectively, for every two‐fold dose increase.
2. Based on an informal comparison rosuvastatin was determined to be about three‐fold more potent than atorvastatin in reducing total cholesterol and LDL‐cholesterol.
3. The percentage LDL‐lowering effect of rosuvastatin was similar in individuals with familial hypercholesterolaemia and the general population.
4. All doses of rosuvastatin did not change WDAEs as compared to placebo (RR 0.84; 95% CI 0.48 to 1.47). However, there is a high risk of bias for this outcome and thus it cannot be considered a reliable estimate.Implication of these findings
Rosuvastatin lowers lipid parameters in a dose‐related fashion that is similar to but more potent than atorvastatin; 30 mg of atorvastatin is required to lower total cholesterol and LDL‐cholesterol as much as 10 mg of rosuvastatin.
Implications for research
1. More randomized controlled trials (RCTs) for rosuvastatin doses of 1 and 80 mg/day are needed as well as for higher and lower doses to improve the estimate of the dose‐response efficacy of rosuvastatin.
2. All placebo‐controlled RCTs must accurately report WDAEs.
3. All trials should report the effects separately in men and women so it is possible to determine if there are any clinically significant dose‐related sex differences.
4. Further systematic reviews comparing the lipid‐lowering effect of rosuvastatin both directly and indirectly with other statins are needed.Get full text at The Cochrane Library
Evidence Central is an integrated web and mobile solution that helps clinicians quickly answer etiology, diagnosis, treatment, and prognosis questions using the latest evidence-based research. Complete Product Information.