Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials.

Abstract

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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.

INTERPRETATION:

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.

FUNDING:

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.

• Authors: Cholesterol Treatment Trialists' (CTT) Collaboration, William Herrington, Jonathan Emberson, Borislava Mihaylova, Lisa Blackwell, Christina Reith, Marit Solbu, Patrick Mark, Bengt Fellström, Alan Jardine, Christoph Wanner, Hallvard Holdaas, Jordan Fulcher, Richard Haynes, Martin Landray, Anthony Keech, John Simes, Rory Collins, Colin Baigent
• Journal: The lancet. Diabetes & endocrinology (Lancet Diabetes Endocrinol) Vol. 4 Issue 10 Pg. 829-39 (10 2016) ISSN: 2213-8595 [Electronic] England
• PMID: 27477773 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors

Topics

• Aged
• Cholesterol, LDL (blood)
• Female
• Glomerular Filtration Rate
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Kidney (drug effects, physiopathology)
• Kidney Function Tests
• Male
• Middle Aged
• Randomized Controlled Trials as Topic
• Renal Insufficiency, Chronic (blood, complications, drug therapy)
• Treatment Outcome
• Vascular Diseases (blood, complications, drug therapy)