Statin is commonly used to lower LDL cholesterol levels in the general population, which reduces the risk of cardiovascular disease [8, 13]. Moreover, many studies have shown the substantial benefits of statin therapy in patients with cardiovascular disease . However, lack of information on the efficacy and safety of statin therapy in patients with CKD has limited the use of statins for these patients. We excluded patients with end-stage renal disease from our study, which is associated with extremely high cardiovascular morbidity and mortality rates, the co-morbidity of end-stage of renal disease, may be difficult to reverse in this phase [12, 37]. This study was based on RCTs and investigated any possible correlation between statin therapy and the outcomes of any cardiovascular-related disease in patients with early to moderate renal disease (Kidney Disease Outcomes Quality Initiative [K/DOQI stage 1–4]).
This large quantitative review, including 42,426 individuals with a broad range of baseline characteristics, suggests that statin therapy could lead to a 24% reduction in the risk of cardiovascular disease, a 21% reduction in the risk of total mortality, and a 23% reduction in the risk of cardiovascular mortality in patients with mild to moderate CKD. A previous study indicated that statin therapy reduced the risk of cardiovascular disease, total mortality, and cardiovascular death in a subgroup analysis of pre-dialysis patients . These findings were similar to the results of our study. Our main findings also support the conclusion of the Pravastatin Pooling Project (PPP 2004), which was a pooled analysis of three major statin studies on the subject level and demonstrated that statin therapy also appeared to reduce the incidence of cardiovascular disease and total mortality rate in patients with mild to moderate CKD . Furthermore, our study also reported the results of myocardial infarction and stroke and concluded that statin therapy also contributed to a 34% reduction in the risk of myocardial infarction and a 30% reduction in the risk of stroke.
The outcome of cardiovascular disease, cardiovascular death, and total mortality was also reported in two previous meta-analyses [15, 38]. Our meta-analysis extended this by including 8 additional randomized trials with patients across a wider background of cardiovascular risk [14, 25, 26, 28–30, 32, 33]. We also performed more detailed subgroup analysis to explore whether the effects varied among different patients. We did not include trials with small sample size or short duration because cardiovascular events and CKD might not be clearly defined in these small trials, or the risk for outcome might not be accurate owing to insufficient observation times.
Some important factors such as baseline creatinine level, baseline GFR, and cardiovascular disease history may affect the results. The effects of statin therapy on cardiovascular disease in patients with baseline creatinine levels >1.5 mg/dL was not statistically significant. Similar effects were also found in a subgroup analysis of total mortality in patients with baseline creatinine levels >1.5 mg/dL, baseline GFR <60 mL · min-1 · 1.73 m-2, and a cardiovascular disease history. The results emphasized that statin therapy should be examined more carefully in these particular cases. However, further studies are needed to substantiate these conclusions.
A subgroup analysis of baseline LDL cholesterol levels and LDL lowering rates in patients with cardiovascular disease indicated no significant differences, although there were some benefits in the prevention of cardiovascular risk in total analysis. A possible reason could be that although LDL cholesterol level is considered an important risk factor for cardiovascular disease in patients, this strong correlation was attenuated by non-traditional cardiovascular risk factors such as the severity of kidney disease, oxidative stress, and inflammation in patients with renal insufficiency [32, 33, 36, 39, 40]. This may suggest that cardiovascular risk in patients with CKD, which is a complex mechanism, does not have a simple connection with dyslipidaemia, and may be a less effective indicator of dyslipidaemia as the major causal factor. Therefore, the benefits of statin therapy on cardiovascular disease in patients with mild to moderate CKD could not be explained by a differential action on lipid levels.
The effect of statin therapy on renal function could be qualitatively evaluated in nine included studies [24–26, 28–33]. Five studies [14, 24, 31–33] have reported stable or no adverse effects on kidney function. Moreover, three trials [25, 26, 29] reported the renoprotective effect observed in the treatment group compared with the placebo group, and only one trial  reported adverse effects on kidney function. A possible reason could be that statin therapy reduces inflammation, which may slow the progression of tubulointerstitial nephritis, although a transient increase in proteinuria may be caused, and may protect against long-term renal damage . Therefore, we may conclude that statin therapy has no serious adverse effects on kidney function, and is possibly beneficial to kidney function; however, these arguments definitely need further study with more detailed data on kidney function at the patient level.
Our analysis also found that statin therapy has no significant drug-related side effects such as rhabdomyolysis, cancer, or change in creatine phosphokinase levels compared with the control group. However, these conclusions might be unreliable because only a small number of trials were included in such subsets.
Our study also has some potential limitations. First, our result was based on published data, whereas individual patient data and original data were not available, which may limit the effective assessment of drug effects and safety. Second, the evaluation index of renal function differed in the included trials, which may affect the classification of CKD. Third, baseline characteristics such as the statin type, dosage, disease history, severity of CKD, and follow-up duration varied among included trials, which may have caused some heterogeneity. Last, publication bias was unavoidable in our study.