Abstract
Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain. We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol. Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR. Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits. UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.
Highlights
Statin-based therapy is widely used among patients with chronic kidney disease to reduce the risk of atherosclerotic events, but there is uncertainty about the effects of such treatment among patients with an estimated glomerular filtration rate below 30 mL/min per 1·73 m2
Procedures During the planning of the analyses, we identified major differences in the proportions of cardiac deaths attributed to coronary heart disease in the AURORA trial[3] compared with other trials of statin-based regimens among patients on dialysis.[2,4]
Data were unavailable for three trials: one trial of atorvastatin versus placebo in 4731 patients with a history of cerebrovascular disease;[46] one trial of atorvastatin versus usual care in 1600 patients with coronary heart disease;[47] and one trial of simvastatin plus ezetimibe versus placebo in 1873 patients with aortic stenosis.[48]
Summary
Statin-based therapy is widely used among patients with chronic kidney disease to reduce the risk of atherosclerotic events (myocardial infarction and ischaemic stroke), but there is uncertainty about the effects of such treatment among patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min per 1·73 m2. Meta-analyses published up to now have several limitations.[5,6,7,8,9,10,11,12,13,14] First, in a meta-analysis of individual participant data from large trials of statins,[16] the relative effects of statin therapy on major vascular events in a wide range of patients were proportional to the absolute magnitude of the reduction in LDL cholesterol. The extent to which www.thelancet.com/diabetes-endocrinology Vol 4 October 2016
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