Statins Beneficial in Wide Range of Patients With CKD

Veronica Hackethal, MD

August 08, 2016

Statins decrease major cardiovascular events in mild to moderate chronic kidney disease (CKD). However, these benefits decrease with declining kidney function and may not apply to dialysis patients, according to a meta-analysis published online July 28 in Lancet Diabetes & Endocrinology.

The data suggest statins may benefit a "wide range" of patients with CKD. "In patients with [CKD], statin-based regimens should be chosen to maximise the absolute reduction in [low-density lipoprotein (LDL)] cholesterol to achieve the largest treatment benefits," write the authors, who were part of the Cholesterol Treatment Trialists' (CTT) Collaboration.

However, the results are not without some caveats.

"Our results show that, even after allowing for somewhat smaller reductions in LDL cholesterol as [glomerular filtration rate (GFR)] declines, there is a trend towards smaller relative risk reductions for major coronary events and strokes. In particular, there was little evidence that statin-based therapy was effective in patients starting treatment after dialysis had been initiated," they write.

The study also highlighted that the greater the LDL reduction, the larger the benefit of statins. Achieving greater LDL reduction, however, generally means higher statin doses, which may increase the risk for myopathy in some patients with renal impairment.

The researchers drew on data from the CTT Collaboration clinical trials database and encompassed 28 trials covering 183,419 individuals, including those on dialysis and kidney transplant patients. The analysis included AURORA, a key trial of dialysis patients. Because the AURORA trial used a different definition for coronary death than other trials, researchers reclassified this outcome to standardize assessment. They also standardized results to account for differences in the amount of LDL reduction across trials.

Overall, results showed that statins decreased the risk of having a first major vascular event by 21% per mmol/L decrease in LDL cholesterol (rate ratio, 0.79; 95% confidence interval [CI], 0.77 - 0.81; P < .0001). Major coronary events and stroke both decreased with statin use (rate ratio, 0.76 [95% CI, 0.73 - 0.79] and 0.84 [95% CI, 0.80 - 0.89], respectively).

The benefits of statins decreased, along with declining estimated GFR (eGFR; P = .008 for trend), mainly related to major coronary events (P = .01 for trend) and stroke (P = .07 for trend):

  • eGFR ≥60 mL/minute per 1.73 m2: RR, 0.78; 99% CI, 0.75 - 0.82

  • eGFR 45 to <60 mL/minute per 1.73 m2: RR, 0.76; 99% CI, 0.70 - 0.81

  • eGFR 30 to <45 mL/minute per 1.73 m2: RR, 0.85; 99% CI, 0.75 - 0.96

  • eGFR <30 mL/minute per 1.73 m2 and not on dialysis: RR, 0.85; 99% CI, 0.71 - 1.02

  • Dialysis: RR, 0.94; 99% CI, 0.79 - 1.11

Moreover, statins decreased the risk for coronary revascularization procedures by 25% per 1.0 mmol/L decrease in LDL (RR, 0.75; 95% CI, 0.73 - 0.78; P < .0001), which was not significantly affected by baseline renal function (P = .9 for trend).

Statins also decreased vascular death by 12% per 1.0 mmol/L decrease in LDL cholesterol (RR, 0.88; 95% CI, 0.85 - 0.91; P < .0001), with smaller risk reductions in those with more impaired baseline renal function (P = .03 for trend).

Statins did not significantly affect nonvascular mortality, regardless of eGFR.

"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 also provide further evidence that the relative risk reductions achieved for major cardiovascular events diminish in magnitude with reducing kidney function," write Muh Geot Wong, MD, PhD, and Vlado Perkovic, MD, PhD, both from the University of Sydney in Australia, in a linked editorial.

They emphasized the feasibility and importance of large clinical trials in patients with advanced CKD. In particular, they highlighted the potential cardiovascular benefits of new treatments such as PSCK9 inhibitors and studying whether statins can benefit kidney function.

"[The results from this trial] raise further questions about the effects of lipid-lowering in advanced disease and highlight the importance of new trials with highly effective agents in this population. By defining what we still do not know, this analysis will hopefully encourage further studies that improve outcomes for this high-risk patient group," they conclude.

The study was funded by UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, and the Australian National Heart Foundation. Most of the trials included in the meta-analysis were supported by the pharmaceutical industry. One or more authors reports grants, personal or other fees, and/or travel from one or more of the following: Merck, Novartis, Pfizer, Astellas, Opsona, AstraZeneca, Boehringer Ingelheim, Amgen, Vifor, Sanofi, AbbVie, Otsuka Pharma Scandinavia, Janssen, Novo Nordisk, GlaxoSmithKline, Sanofi Genzyme, Bristol-Myers Squibb, Sandoz, Alexion, Tengion, Pharmalink, BioConcept, Alimenta Medical, TransCutan, Human Life, Abbott, Amgen, Eli Lilly, Merck, Roche Diagnostics, Solvay, Sanofi -Aventis, British Heart Foundation, Medical Research Council, Cancer Research UK, and/or Oxford University. Dr Perkovic reports steering committee or advisory board membership on trials funded by AbbVie, Boehringer Ingelheim, Janssen, GlaxoSmithKline, and Bristol-Myers Squibb; receiving honoraria from Boehringer Ingelheim, AstraZeneca, Pfizer, Roche, Merck, Eli Lilly, and Servier; receiving a grant for a clinical trial from Baxter and Pfizer; and being a member of the regional coordinating center for the SHARP. He has also published and served on other trial steering committees with several of the SHARP investigators. Dr Wong has disclosed no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online July 28, 2016. Article full text, Comment full text

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