Cardiovascular disease (CVD) is the most frequent cause of death in people with early
stages of chronic kidney disease (CKD), for whom the absolute risk of cardiovascular
events is similar to people who have existing coronary artery disease. This is an
update of a review published in 2009, and includes evidence from 27 new studies (25,068
participants) in addition to the 26 studies (20,324 participants) assessed previously;
and excludes three previously included studies (107 participants). This updated review
includes 50 studies (45,285 participants); of these 38 (37,274 participants) were
meta-analysed.
To evaluate the benefits (such as reductions in all-cause and cardiovascular mortality,
major cardiovascular events, MI and stroke; and slow progression of CKD to end-stage
kidney disease (ESKD)) and harms (muscle and liver dysfunction, withdrawal, and cancer)
of statins compared with placebo, no treatment, standard care or another statin in
adults with CKD who were not on dialysis.
We searched the Cochrane Renal Group's Specialised Register to 5 June 2012 through
contact with the Trials' Search Co-ordinator using search terms relevant to this review.
Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins
with placebo, no treatment, standard care, or other statins, on mortality, cardiovascular
events, kidney function, toxicity, and lipid levels in adults with CKD not on dialysis
were the focus of our literature searches.
Two or more authors independently extracted data and assessed study risk of bias.
Treatment effects were expressed as mean difference (MD) for continuous outcomes (lipids,
creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes
(major cardiovascular events, all-cause mortality, cardiovascular mortality, fatal
or non-fatal myocardial infarction (MI), fatal or non-fatal stroke, ESKD, elevated
liver enzymes, rhabdomyolysis, cancer and withdrawal rates) with 95% confidence intervals
(CI).
We included 50 studies (45,285 participants): 47 studies (39,820 participants) compared
statins with placebo or no treatment and three studies (5547 participants) compared
two different statin regimens in adults with CKD who were not yet on dialysis. We
were able to meta-analyse 38 studies (37,274 participants).The risk of bias in the
included studies was high. Seven studies comparing statins with placebo or no treatment
had lower risk of bias overall; and were conducted according to published protocols,
outcomes were adjudicated by a committee, specified outcomes were reported, and analyses
were conducted using intention-to-treat methods. In placebo or no treatment controlled
studies, adverse events were reported in 32 studies (68%) and systematically evaluated
in 16 studies (34%).Compared with placebo, statin therapy consistently prevented major
cardiovascular events (13 studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79),
all-cause mortality (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91),
cardiovascular death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87)
and MI (8 studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72). Statins had uncertain
effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to 1.12).Potential
harms from statin therapy were limited by lack of systematic reporting and were uncertain
in analyses that had few events: elevated creatine kinase (7 studies, 4514 participants;
RR 0.84, 95% CI 0.20 to 3.48), liver function abnormalities (7 studies, RR 0.76, 95%
CI 0.39 to 1.50), withdrawal due to adverse events (13 studies, 4219 participants;
RR 1.16, 95% CI 0.84 to 1.60), and cancer (2 studies, 5581 participants; RR 1.03,
95% CI 0.82 to 130).Statins had uncertain effects on progression of CKD. Data for
relative effects of intensive cholesterol lowering in people with early stages of
kidney disease were sparse. Statins clearly reduced risks of death, major cardiovascular
events, and MI in people with CKD who did not have CVD at baseline (primary prevention).
Statins consistently lower death and major cardiovascular events by 20% in people
with CKD not requiring dialysis. Statin-related effects on stroke and kidney function
were found to be uncertain and adverse effects of treatment are incompletely understood.
Statins have an important role in primary prevention of cardiovascular events and
mortality in people who have CKD.