Article type
Year
Abstract
Background: Statins are recognised as an effective treatment for lowering cholesterol levels and reducing the risk of cardiovascular diseases. They have been widely studied in basic and human research and there are no systematic reviews of statins across animal models.
Objectives: We explored differences in the efficacy of statins in three popular animal models: mice, rats and rabbits, using the technique of systematic review (i.e. Cochrane methods). We also explored whether the reporting was accurate, and the risk of bias.
Methods: We searched MEDLINE and EMBASE. Two independent reviewers assessed the eligibility, extracted study details and biochemical blood parameters, blood pressure, myocardial infarction and survival. Weighted and standard mean difference random effects meta-analysis was used to measure overall efficacy in specified species, strains and subgroups.
Results: We analyzed 161 studies. Most papers did not use randomization (55%) or blinding (88%) and their reporting presented several shortcomings. Statins lowered total cholesterol in all species though with large differences in the effect size: 30% in rabbits, $-20$% in mice and $-10$% in rats. Many meta-analyses suffered substantial heterogeneity despite the postulated limited biological variability in single species and strains. Few studies considered strains at high risk of cardiovascular diseases even though mimic human cardiovascular diseases better or examined hard outcomes. A risk of pubblication bias our data also suggested. About 45% of publications identified report no significant findings on total cholesterol.
Conclusions: Although statins showed substantial efficacy in animal models, the preclinical data on conditions mimicking the human pathologies for which the drugs are clinically indicated and utilized are often scarce, incomplete and at risk of bias. This study raises a number of concerns, particularly about the reliability and quality of animal experiments that may drive future clinical trials in humans.
Objectives: We explored differences in the efficacy of statins in three popular animal models: mice, rats and rabbits, using the technique of systematic review (i.e. Cochrane methods). We also explored whether the reporting was accurate, and the risk of bias.
Methods: We searched MEDLINE and EMBASE. Two independent reviewers assessed the eligibility, extracted study details and biochemical blood parameters, blood pressure, myocardial infarction and survival. Weighted and standard mean difference random effects meta-analysis was used to measure overall efficacy in specified species, strains and subgroups.
Results: We analyzed 161 studies. Most papers did not use randomization (55%) or blinding (88%) and their reporting presented several shortcomings. Statins lowered total cholesterol in all species though with large differences in the effect size: 30% in rabbits, $-20$% in mice and $-10$% in rats. Many meta-analyses suffered substantial heterogeneity despite the postulated limited biological variability in single species and strains. Few studies considered strains at high risk of cardiovascular diseases even though mimic human cardiovascular diseases better or examined hard outcomes. A risk of pubblication bias our data also suggested. About 45% of publications identified report no significant findings on total cholesterol.
Conclusions: Although statins showed substantial efficacy in animal models, the preclinical data on conditions mimicking the human pathologies for which the drugs are clinically indicated and utilized are often scarce, incomplete and at risk of bias. This study raises a number of concerns, particularly about the reliability and quality of animal experiments that may drive future clinical trials in humans.