Statins for people with kidney diseaseBMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39483.665139.80 (Published 20 March 2008) Cite this as: BMJ 2008;336:624
- Catherine M Clase, associate professor of medicine
In the accompanying paper, Strippoli and colleagues report a meta-analysis of the benefits and harms of statins in patients with chronic kidney disease. They report outcomes for people with low glomerular filtration rate, those on dialysis, and those with kidney transplants.1
Chronic kidney disease (glomerular filtration rate < 60 ml/min/1.73 m2 or urine abnormalities) and cardiovascular disease often coexist; chronic kidney disease also predicts cardiovascular events. A recent meta-analysis reported that low glomerular filtration rate was associated with an unadjusted relative risk of 2.5 (95% confidence interval 1.4 to 4.3) for cardiovascular events.2 In adjusted analyses, some of this effect is explained by the high prevalence of traditional risk factors for cardiovascular disease in people with low glomerular filtration rate or albuminuria.3 4 However, non-traditional risk factors such as anaemia (which in patients on dialysis predicts left ventricular hypertrophy, systolic dysfunction, and congestive heart failure5) and factors favouring vascular calcification (which in patients on dialysis predicts death6) may contribute to death from cardiovascular disease in people with a low glomerular filtration rate or those on dialysis. So statins may not be as effective for preventing cardiovascular events in these groups as they are in the general population.7 Perhaps because of this concern, or because of worries about increased harm or polypharmacy, people with low glomerular filtration rate are less likely to be prescribed statins after a coronary event.8
In people at high risk of cardiovascular events because of established cardiovascular disease or conventional risk factors, does a low glomerular filtration rate affect the benefits or harms of statins?In Strippoli and colleagues’ analysis of patients with pre-dialysis (stages I-IV) chronic kidney disease, which includes five studies, 18 176 people with low glomerular filtration rate, and 1591 events, the relative risk of all cause mortality was 0.81 (0.74 to 0.89) in patients randomised to statins. This is consistent with data from the general population9 10: statins produced a clinically important reduction in the overall risk of death of 19%. However, this analysis is based on studies mainly involving patients with a glomerular filtration rate above 30 ml/min/1.73 m2 (stages I-III). Only a few people who are not on dialysis and have a glomerular filtration rate below 30 ml/min/1.73 m2 (stage IV) have been included in trials.
The meta-analyses of studies of people on dialysis and those with kidney transplants found no benefit in terms of all cause mortality. Strong trends to reductions in death from cardiovascular events were seen in both groups, however, with point estimates of a 17% reduction in death from cardiovascular disease in people on dialysis and 32% in people with kidney transplants. In terms of harm, they found no significantly increased risk of abnormalities of liver function or creatine kinase (relative risk 1.5, 0.9 to 2.6).
These data suggest that the benefit of statins seen in the general population also applies to people with low glomerular filtration rate, those on dialysis, and those with kidney transplants, provided they have established cardiovascular disease or a cardiovascular risk profile that justifies treatment.
In people who are at high risk of cardiovascular disease mainly because of chronic kidney disease (low glomerular filtration rate or albuminuria), do statins prevent cardiovascular events?No large scale randomised controlled trials are available to answer this question. The SHARP (study of heart and renal protection) should be able to answer this question directly. The trial has enrolled 9000 people who are on dialysis or have a low glomerular filtration rate, but no previous cardiac event, and has randomised them to combined simvastatin and ezetimibe or to placebo.7 11 But until these results are available, low glomerular filtration rate or dialysis alone should not be considered indications for treatment with statins.
Finally, in people with low glomerular filtration rate, do statins prevent progression of renal insufficiency and progression to end stage renal disease?Strippoli and colleagues found that statins modestly reduced proteinuria but did not affect the rate of decline of glomerular filtration rate. A previous meta-analysis found similar effects on proteinuria and detected a small reduction in the rate of decline of glomerular filtration rate,12 perhaps because a difference in inclusion criteria led to increased power. None the less, surrogate outcomes such as these are unconvincing, and no trials have reported the clinically important outcome of progression to end stage renal disease. The effect of treatment to lower cholesterol on this outcome will be looked at in a secondary analysis of the SHARP study.
Available evidence suggests that the threshold of cardiovascular risk for treating most patients with a low glomerular filtration rate (30-60 ml/min/1.73 m2) should be the same as for those with a higher rate. This approach should probably be extended to people with a glomerular filtration rate below 30 ml/min/1.73 m2, those on dialysis, and those with transplants. The SHARP trial will definitively answer the question of whether low glomerular filtration rate or dialysis are indications for cholesterol lowering treatment for the prevention of cardiovascular events and progression to end stage renal disease. Pending its results, data do not support the use of statins for these reasons.
Competing interests: CMC has organised educational rounds sponsored by drug companies that make statins.
Provenance and peer review: Commissioned; not externally peer reviewed.