Bibliographic record
Abstract
Background This represents the first update of this review, which was published in 2012. 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. Objectives Primary objective To quantify the effects of various doses of atorvastatin on serum total cholesterol, low‐density lipoprotein (LDL)‐cholesterol, high‐density lipoprotein (HDL)‐cholesterol and triglycerides in individuals with and without evidence of cardiovascular disease. The primary focus of this review was determination of the mean per cent change from baseline of LDL‐cholesterol. Secondary objectives • To quantify the variability of effects of various doses of atorvastatin. • To quantify withdrawals due to adverse effects (WDAEs) in placebo‐controlled randomised controlled trials (RCTs). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2013), MEDLINE (1966 to December Week 2 2013), EMBASE (1980 to December Week 2 2013), Web of Science (1899 to December Week 2 2013) and BIOSIS Previews (1969 to December Week 2 2013). We applied no language restrictions. Selection criteria 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 three to 12 weeks. Data collection and analysis Two review authors independently assessed eligibility criteria for studies to be included and extracted data. We collected information on withdrawals due to adverse effects from placebo‐controlled trials. Main results In this update, we found an additional 42 trials and added them to the original 254 studies. The update consists of 296 trials that evaluated dose‐related efficacy of atorvastatin in 38,817 participants. Included are 242 before‐and‐after trials and 54 placebo‐controlled RCTs. Log dose‐response data from both trial designs revealed linear dose‐related effects on blood total cholesterol, LDL‐cholesterol, HDL‐cholesterol and triglycerides. 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. Over this range, blood LDL‐cholesterol is decreased by 37.1% to 51.7% (Summary of findings table 1). 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. Subgroup analyses suggested that the atorvastatin effect was greater in females than in males and was greater in non‐familial than in familial hypercholesterolaemia. 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. 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). Authors' conclusions This update resulted in no change to the main conclusions of the review but significantly increases the strength of the evidence. Studies show that atorvastatin decreases blood total cholesterol and LDL‐cholesterol in a linear dose‐related manner over the commonly prescribed dose range. New findings include that atorvastatin is more than three‐fold less potent than rosuvastatin, and that the cholesterol‐lowering effects of atorvastatin are greater in females than in males and greater in non‐familial than in familial hypercholesterolaemia. This review update does not provide a good estimate of the incidence of harms associated with atorvastatin because included trials were of short duration and adverse effects were not reported in 37% of placebo‐controlled trials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.017 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".