Statin benefits dependent on baseline kidney function
medwireNews: The benefits of statin-based treatments among patients with chronic kidney disease diminish with decreasing estimated glomerular filtration rate (eGFR), with little evidence of any benefit for patients on dialysis, results of a large meta-analysis show.
Members of the Cholesterol Treatment Trialists’ (CTT) Collaboration analysed individual data for 183,419 participants (mean age 62.6 years, 73% men) of 28 trials examining the effects of statin-based therapy on major vascular events, defined as major coronary events (nonfatal myocardial infarction or coronary death), coronary revascularisation, stroke and cause-specific mortality.
Overall, statin-based therapy significantly reduced the risk of a first major vascular event by 21% per mmol/L reduction in LDL cholesterol, and the risks of major coronary events and stroke by 24% and 16%, respectively.
However, the researchers found that the relative effect on major vascular events decreased significantly with decreasing baseline eGFR.
Specifically, participants with a baseline eGFR of at least 60 mL/min per 1.73 m2 had a significant 22% lower rate of major vascular events per mmol/L reduction in LDL cholesterol, compared with 24% for an eGFR of 45 to less than 60 mL/min per 1.73 m2 and 15% for eGFR of 30 to below 45 mL/min per 1.73 m2.
Patients with a baseline eGFR below 30 mL/min per 1.73 m2 and not on dialysis had a nonsignificant 15% lower rate of major vascular events per mmol/L reduction in LDL cholesterol, while those on dialysis had a nonsignificant 6% reduction.
The researchers note that this trend was mainly due to smaller proportional effects with lower eGFR on major coronary events and stroke.
However, they also point out in The Lancet Diabetes and Endocrinology that the decreased vascular benefit with lower renal function might be due, in part, to the fact that “the proportion of cardiac deaths attributable to coronary heart disease—and, hence, potentially avoidable by reducing LDL cholesterol—becomes smaller as eGFR declines.”
The study data also showed a 12% reduction in vascular deaths per mmol/L reduction in LDL cholesterol, with a similar significant trend for smaller proportional effects with worsening baseline renal function. However, reducing LDL cholesterol with statin-based therapy had no effect on nonvascular mortality, irrespective of eGFR.
And although statin-based treatment reduced the need for coronary revascularisation procedures by 25% per mmol/L LDL cholesterol reduction overall, there was no trend by baseline renal function for this outcome.
In an accompanying commentary, Muh Geot Wong and Vlado Perkovic, both from the University of Sydney, New South Wales, Australia, write: “The results provide convincing evidence that statin therapy is beneficial in a wide range of patients with chronic kidney disease, with benefits proportional to the absolute LDL cholesterol reduction achieved.”
They add that it is unclear whether the “smaller relative risk reductions in patients with end-stage kidney disease result from a true lack of efficacy of statins in these individuals”, or whether larger event differences are “being drowned out by a larger number of less statin-sensitive cardiovascular events such as arrhythmias and heart failure.”
By Laura Cowen
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