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Cited by 189Chronic Kidney Disease and DiabetesGenetics, Aging, and Longevity in Model OrganismsAlzheimer's disease research and treatments

Effects of Fibrates in Kidney Disease

Open access
Jun, Min, Zhu, Bin, Tonelli, Marcello, Jardine, Meg J., Patel, Anushka, Neal, Bruce, Liyanage, Thaminda, Keech, Anthony +2 more·2012·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2012.07.049
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Abstract

Objectives The purpose of this systematic review and meta-analysis was to determine the efficacy and safety of fibrate therapy in the chronic kidney disease (CKD) population.Background Fibrate therapy produces modest cardiovascular benefits in people at elevated cardiovascular risk. There is limited evidence about the clinical benefits and safety of fibrate therapy in the CKD population.Methods MEDLINE, EMBASE, and the Cochrane Library were systematically searched (1950 to January 2012) for prospective randomized controlled trials assessing the effects of fibrate therapy compared with placebo in people with CKD or on kidney-related outcomes were included.Results Ten studies including 16,869 participants were identified. In patients with mild-to-moderate CKD (estimated glomerular filtration rate [eGFR] ≤60 ml/min/1.73 m(2)), fibrates improved lipid profiles (lowered total cholesterol [-0.32 mmol/l, p = 0.05] and triglyceride levels [-0.56 mmol/l, p = 0.03] but not low-density lipoprotein cholesterol [-0.01 mmol/l, p = 0.83]; increased high-density lipoprotein cholesterol [0.06 mmol/l, p = 0.001]). In people with diabetes, fibrates reduced the risk of albuminuria progression (relative risk [RR]: 0.86; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.02). Serum creatinine was elevated by fibrate therapy (33 μmol/l, p < 0.001), calculated GFR was reduced (-2.67 ml/min/1.73 m(2), p = 0.01) but there was no detectable effect on the risk of end-stage kidney disease (RR: 0.85; 95% CI: 0.49 to 1.49; p = 0.575). In patients with eGFR of 30 to 59.9 ml/min/1.73 m(2), fibrates reduced the risk of major cardiovascular events (RR: 0.70; 95% CI: 0.54 to 0.89; p = 0.004) and cardiovascular death (RR: 0.60; 95% CI: 0.38 to 0.96; p = 0.03) but not all-cause mortality. There were no clear safety concerns specific to people with CKD but available data were limited.Conclusions Fibrates improve lipid profiles and prevent cardiovascular events in people with CKD. They reduce albuminuria and reversibly increase serum creatinine but the effects on major kidney outcomes remain unknown. These results suggest that fibrates have a place in reducing cardiovascular risk in people with mild-to-moderate CKD.

Integrity signals

Registry

Crossref · 10.1016/j.jacc.2012.07.049

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

17 of 47 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Dyslipidemia is a risk factor for progressive kidney disease.

    “While dyslipidemia is a risk factor for progressive kidney disease (8,10,20,21)”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [8] Fox, 2004, Predictors of new-onset kidney disease in a community-based population, JAMA source
    • cites [10] Muntner, 2000, Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study, Kidney Int source
    • cites [20] Schaeffner, 2003, Cholesterol and the risk of renal dysfunction in apparently healthy men, J Am Soc Nephrol source
    • cites [21] Manttari, 1995, Effects of hypertension and dyslipidemia on the decline in renal function, Hypertension source
  • Premisecitation

    There have been conflicting reports regarding the impact of fibrate therapy on kidney function.

    “there have been conflicting reports regarding the impact of fibrate therapy on kidney function (24,25).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [24] Davis, 2011, Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study, Diabetologia source
    • cites [25] Tonelli, 2004, Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease, Am J Kidney Dis source
  • Interpretationcitation

    The drug-induced elevations in serum creatinine do not reflect a true deterioration of renal function.

    “These potential explanations have supported the view that the drug-induced elevations in serum creatinine does not reflect a true deterioration of renal function”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [44] Chen, 2011, Fenofibrate reversibly increases serum creatinine level in chronic kidney disease patients by reducing glomerular filtration rate, Acta Nephrologica
    • cites [50] Mychaleckyj, 2012, Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants, Diabetes Care source

      The Abstract Conclusions report that fenofibrate-associated creatinine increases were reversible, with complete reversal after 51 days off the drug. But the Conclusions also say cystatin C changed similarly, ruling out a creatinine-specific explanation; the paper does not establish that renal function was unaffected during treatment. Page numbers were not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    In a post-hoc analysis from the FIELD study, plasma creatinine levels 8 weeks after withdrawal were significantly lower in participants who had received fenofibrate compared to placebo.

    “A post-hoc analysis from the FIELD study reported that plasma creatinine levels in a cohort of 661 “substudy washout participants” 8 weeks after withdrawal from study treatment were significantly lower in participants who had received fenofibrate compared to placebo (p Ͻ 0.001)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] Davis, 2011, Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study, Diabetologia source

      The Results report that, among 661 washout sub-study participants, plasma creatinine was significantly lower in the fenofibrate group than in the placebo group 8 weeks after treatment withdrawal (p<0.001). However, the Randomisation and interventions section says the washout analyses were pre-specified six months before unmasking, rather than post-hoc. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Fibric acid derivatives reduce the risk of cardiovascular events.

    “Fibric acid derivatives are effective in improving lipid profiles and reducing the risk of cardiovascular events with evidence showing greater efficacy of fibrates in people with baseline hypertriglyceridemia (19,42).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [19] Jun, 2010, Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis, Lancet source
    • cites [42] McCullough, 2011, Treatment of hypertriglyceridemia with fibric Acid derivatives: impact on lipid subfractions and translation into a reduction in cardiovascular events, Rev Cardiovasc Med source
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingcitation

    In one study, a reduction in eGFR during fibrate treatment was reversed off therapy, with eGFR levels higher in the group treated with long-term fenofibrate (total eGFR loss 5.8 vs 9.9 ml/min/1.73m2, p<0.001).

    “A reduction in eGFR was noted during study treatment, but this was reversed off therapy where eGFR levels were higher in the group that had been treated with long-term fenofi- brate (total eGFR loss 5.8 vs. 9.9 ml/min/1.73m 2 , p Ͻ 0.001) (24).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Davis, 2011, Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study, Diabetologia source

      The Results report slower eGFR loss during long-term treatment (5.8 vs 9.9 ml/min/1.73 m², p<0.001) and, in the washout substudy, higher eGFR after treatment withdrawal in the fenofibrate group. However, the cited 5.8 vs 9.9 figures describe the on-treatment interval, not total loss measured after withdrawal; the washout substudy reports 1.9 vs 6.9 instead. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Double blinding was reported in 4 studies, with 1 reporting that renal outcomes such as serum creatinine measurements were performed by individuals blinded to study treatment.

    “Double blinding was reported to have been used in 4 studies (32,35,37,38), with 1 reporting that renal outcomes such as serum creatinine measurements were performed by individuals blinded to study treatment (38).”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [32] Levin, 2000, A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate, Clin Nephrol
    • cites [35] Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med;362:1563–74. source

      The Methods (Study Procedures; page unavailable) report masked administration of fenofibrate or placebo, supporting treatment blinding. The Results (Safety; page unavailable) report serum creatinine levels, but our copy does not say that the people measuring creatinine or other renal outcomes were blinded to treatment. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [37] Keech, 2005, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial, Lancet source
    • cites [38] Tonelli, 2004, Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease, Am J Kidney Dis source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The SHARP trial demonstrated that statin-based LDL lowering prevents cardiovascular events in CKD patients, particularly those with early disease.

    “Of note, the recent SHARP (Study of Heart and Renal Protection) trial clearly demonstrated that statinbased LDL lowering prevents cardiovascular events in CKD patients, particularly those with early disease (14).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Baigent, 2011, The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial, Lancet source

      The Discussion reports that simvastatin plus ezetimibe reduced major atherosclerotic events in patients with CKD. But it explicitly says there was no trend toward larger benefit in patients with less severe renal impairment, so the claim that benefit was particularly strong in early disease is not supported. (LLM, conf=0.91)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Study design and conductown data

    Overall, 4 trials had a Jadad score of 4, 1 scored 3, 2 scored 2, and 1 scored 1.

    “Overall, 4 trials had a Jadad score of 4 (24,25,32,35), 1 scored 3 (33), 2 scored 2 (29,31), and 1 scored 1 (30).”
    Quote in the paperNot a substantial claim2 of 7 sources checked
    • cites [24] Davis, 2011, Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study, Diabetologia source

      The Methods and Randomisation and interventions sections identify FIELD as a randomised, double-blind, placebo-controlled trial and describe its randomisation procedure. The paper does not report a Jadad score, so our copy supports identifying it as a trial but cannot verify the citing authors’ score of 4. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [25] Tonelli, 2004, Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease, Am J Kidney Dis source
    • cites [32] Levin, 2000, A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate, Clin Nephrol
    • cites [35] Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med;362:1563–74. source

      The Methods (Study Design) describe one ACCORD Lipid trial, not a quality assessment of eight trials. Searches for “Jadad score” and quality assessment of eight trials found no passage in our copy reporting the claimed score distribution. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [33] Ansquer, 2005, Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS), Am J Kidney Dis source
    • cites [29] Barbir, 1992, Maxepa versus Bezafibrate in hyperlipidemic cardiac transplant recipients, Am J Cardiol source
    • cites [31] Samuelsson, 1997, Effect of gemfibrozil on lipoprotein abnormalities in chronic renal insufficiency: a controlled study in human chronic renal disease, Nephron source

  • May combine two claims.

    Findingnone given

    Gemfibrozil, compared with fenofibrate, tended to be more efficacious in improving triglyceride levels but not total cholesterol, LDL, or HDL levels.

    “Gemfibrozil, compared with fenofibrate, tended to be more efficacious in improving triglyceride levels but not total cholesterol, LDL, or HDL levels.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingnone given

    Adverse events reporting was inconsistent, limiting the conclusions that can be drawn.

    “Adverse events reporting was inconsistent, limiting the conclusions that can be drawn”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    One study reported the use of fish oil as the placebo, which may be a potential confounder as fish oil is known to modify lipid profiles.

    “One study reported the use of fish oil as the placebo, which may be a potential confounder as fish oil is known to modify lipid profiles”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    There were no clear safety concerns specific to people with CKD, but available data were limited.

    “There were no clear safety concerns specific to people with CKD but available data were limited.”
    • Also stated in: § Discussion · plain
      “There were no clear safety concerns specific to the CKD population identified, but available data were limited.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The risk of bias was assessed using key indicators of trial quality.

    “The risk of bias was assessed using key indicators of trial quality (Online Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The effects in people with CKD appeared at least as large as the effects in people with normal kidney function, although formal statistical testing to confirm this was limited by sample size.

    “The effects in people with CKD appeared at least as large as the effects in people with normal kidney function, although formal statistical testing to confirm this was limited by sample size.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The available data support the overall safety and potential benefits of fibrates in CKD.

    “While a large outcome trial conducted specifically in this population is required to more clearly define these effects, the available data support the overall safety and potential benefits of this class of agents (39,40).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Quasching, 1999, Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metablism in chronic hemodialysis patients, J Am Soc Nephrol

      Not checked in the free run.

    • cites [40] 2003, K/DOQI clinical practice guidelines for managing dyslipidemia in chronic kidney disease, Am J Kidney Dis

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The literature search, data extraction, and quality assessment were conducted independently by 2 authors using a standardized approach.

    “The literature search, data extraction, and quality assessment were conducted independently by 2 authors (M.J. and B.Z.) using a standardized approach.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    Study quality was judged by proper conduct of randomization, concealment of treatment allocation, similarity of treatment groups at baseline, provision of eligibility criteria, completeness of follow-up, and use of intention-to-treat analysis, and quantified using the Jadad score.

    “Study quality was judged by the proper conduct of randomization, concealment of treatment allocation, similarity of treatment groups at baseline, the provision of a description of the eligibility criteria, completeness of follow-up, and use of intention-to-treat analysis, and was quantified using the Jadad score (26).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Jadad, 1996, Developing a database of published reports of randomised clinical trials in pain research, Pain source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Any disagreement in abstracted data was adjudicated by a third reviewer.

    “Any disagreement in abstracted data was adjudicated by a third reviewer (V.P.).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The systematic review was performed according to the PRISMA statement for the conduct of meta-analyses of intervention studies.

    “We performed a systematic review of the literature according to the PRISMA statement for the conduct of meta-analyses of intervention studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A recent post hoc analysis of the FIELD study suggested that the acute reduction in eGFR with fibrates is likely to be reversible and may mask an underlying benefit for kidney function.

    “A recent post hoc analysis of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study suggested that this is likely to be reversible and that it may mask an underlying benefit for kidney function.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Formal statistical testing to assess for publication bias was not possible due to limited availability of data and different reporting methods; however, examination of funnel plots of outcomes with 3 or more studies did not suggest publication bias.

    “Formal statistical testing to assess for publication bias was not possible due to the limited avail-ability of data and different reporting methods employed by the studies.However, examination of funnel plots of outcomes with 3 or more studies did not suggest the presence of publication bias (Online Fig. 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Adequate reporting of quality indicators is a validated measure of the quality of trial conduct, strongly related to the internal validity of randomized controlled trials.

    “Adequate reporting of quality indicators is a validated measure of the quality of trial conduct, strongly related to the internal validity of randomized controlled trials (51).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Huwiler-Muntener, 2002, Quality of reporting of randomized trials as a measure of methdologic quality, JAMA source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Hottelart and colleagues reported that serum creatinine was elevated with fenofibrate but without evidence of a reduction in GFR as assessed by inulin clearances.

    “Hottelart and colleagues reported that serum creatinine was elevated with fenofibrate but without evidence of a reduction in GFR as assessed by inulin clearances (46).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Hottelart, 1999, Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency, Nephrologie

  • May combine two claims.

    Study design and conductown data

    Risk of bias assessments showed that some studies were of suboptimal quality in providing adequate descriptions of allocation concealment and lacking double-blinding.

    “the risk of bias assessments of the individual trials have shown that some of the studies were of suboptimal quality in terms of providing adequate descriptions of allocation concealment and lacking the use of double-blinding.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    This systematic review has comprehensively searched the literature for available evidence regarding the effects of fibrate therapy in patients with CKD.

    “This systematic review has comprehensively searched the literature for available evidence regarding the effects of fibrate therapy in patients with CKD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The ACCORD trial participants all received statins but the effects on cardiovascular outcomes in the CKD population have not been reported.

    “The ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial participants all received statins but the effects on cardiovascular outcomes in the CKD population have not been reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Fibrate use is associated with increased hospitalization and nephrologist consultations.

    “associations with increased hospitalization and nephrologist consultations (45)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Zhao, 2012, New fibrate use and acute renal outcomes in elderly adults: a population-based study, Ann Intern Med source

  • May combine two claims.

    Study design and conductown data

    The majority of the studies identified were small and lacked power to detect clinically important effects of fibrates, particularly on advanced renal outcomes such as ESKD.

    “The majority of the studies identified were small and lacked power to detect clinically important effects of fibrates, particularly on advanced renal outcomes such as ESKD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Patients with advanced CKD represent a high-risk population.

    “Patients with advanced CKD represent a high-risk population”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These biases could lead to overestimation of benefit or underestimation of harm.

    “These biases could lead to overestimation of benefit or underestimation of harm.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The risk of bias in some included trials does not invalidate the overall findings.
26 of 26

  • The paper relies on this without support.

    People with CKD have higher triglyceride and lower HDL levels than people without CKD.

    “The higher levels of triglycerides and the lower HDL levels in the CKD population therefore provide a strong rationale for expecting greater magnitudes of benefit in CKD.”

  • The paper relies on this without support.

    The cardiovascular benefits of fibrates outweigh any safety risks in people with kidney disease.

    “These results suggest net benefit if fibrates are used more widely in people with kidney disease.”

  • The paper relies on this without support.

    The subgroup analyses from broader trials provide valid estimates of fibrate effects in people with kidney disease.

    “the available data come from subgroup analyses of trials in broader populations.”

  • The paper relies on this without support.

    The risk of bias in some included trials does not invalidate the overall findings.

    “These biases could lead to overestimation of benefit or underestimation of harm.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The previous meta-analysis did not focus on long-term renal outcomes and did not take into account fibrate-statin co-administration.

    “However, the authors did not focus on long-term renal outcomes and did not take into account fibrate–statin co-administration; a common practice in patients with dyslipidaemia.”

    From The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis of Randomised Studies (2022) · cites this paper as [9]

    The Study selection section lists end-stage kidney disease among the outcomes collected, contrary to the claim that the review did not focus on long-term renal outcomes. The Discussion acknowledges that the effects of combined fibrate–statin treatment remain uncertain, but the review did consider co-administration: it included the ACCORD trial, whose participants received statins. Page numbers are not available for these indexed passages. (LLM, conf=0.86)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • A previous meta-analysis demonstrated efficacy and safety of fibrates on cardiovascular outcomes in people with kidney disease.

    “A meta-analysis previously examined the effect of fibrates on CVD outcomes in people with kidney disease demonstrating efficacy and safety in this patient group [9].”

    From The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis of Randomised Studies (2022) · cites this paper as [9]

    The Abstract and Major Cardiovascular Outcomes section report reduced major cardiovascular events and cardiovascular death in patients with mild-to-moderate kidney disease. The Abstract says there were no clear CKD-specific safety concerns, but safety data were limited; the Discussion also notes a lack of data for severe kidney dysfunction. Thus, the claim overstates how firmly safety was demonstrated across people with kidney disease. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Seven-year data from IMPROVE-IT show that prolonged low LDL-C concentrations are not associated with clear adverse effects.

    “7 year data from the IMPROVE-IT study have shown that prolonged low LDL-C concentrations are not associated with any clear adverse effects [299].”

    From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [299]

  • Ezetimibe was particularly effective in patients with diabetes, with a 15% relative risk reduction (95% CI 6-22%) and a 5.5% absolute risk reduction.

    “Ezetimibe appeared particularly efficacious in patients with DM, with a relative risk reduction of 15% (95% CI 6-22%) and an absolute risk reduction of 5.5% [299].”

    From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [299]

  • In IMPROVE-IT, patients with diabetes had a higher rate of major vascular events than those without diabetes (46% vs 31% 7-year Kaplan-Meier rate in the placebo arm).

    “The subset of patients with DM in IMPROVE-IT had, as expected, a higher rate of major vascular events than patients without DM (46 vs. 31% 7 year Kaplan-Meier rate in the placebo arm).”

    From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [299]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • An included lipid-profile cohort exceeds the stated eGFR cutoff

    Minor

    The paper says all three cited lipid-profile studies concern patients with eGFR ≤60, but Table 1 gives the cited VA-HIT subgroup a mean MDRD eGFR of 62.1. A group with that mean cannot consist entirely of patients at or below 60.

  • Fenofibrate adverse event is attributed to a gemfibrozil study

    Minor

    The epigastric-pain report cites study 31 as a fenofibrate study, but the paper identifies study 31 as a gemfibrozil trial.

  • Studies without placebo comparators were included

    Minor

    The eligibility criteria require a fibrate-versus-placebo comparison, but Table 1 lists fish oil and dietary counseling as comparators in included trials. This affects the description of what the review pooled.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Roberts M, Polkinghorne K, McDonald S, et al. Chapter 12: Cardiovascular mortality in patients who commence dialysis without clinical evidence of cardiovascular disease. ANZDATA Registry 2007 Annual Report. Australia and New Zealand Dialysis and Transplant Registry, Adelaide, South Australia.
  2. Tonelli, 2004, Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease, Am J Kidney Dis, 44, 832, 10.1016/s0272-6386(04)01082-0 · DOI · Paper page
  3. 2003, K/DOQI clinical practice guidelines for managing dyslipidemia in chronic kidney disease, Am J Kidney Dis, 41, S1

Cited by

Sorted by citations

Related

Authors
Jun, M., Zhu, B., Tonelli, M., Jardine, M. J., Patel, A., Neal, B., Liyanage, T., Keech, A., Cass, A., & Perkovic, V.
Affiliations
  • The University of Sydney (AU)
  • Zhejiang Chinese Medical University (CN)
  • University of Alberta (CA)
  • Royal North Shore Hospital (AU)
Corresponding author
Perkovic, Vlado
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2012-11
Volume
60
Issue
20
Pages
2061-2071
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2012.07.049
OpenAlex
W180481652
Cited by
189
References
52
Citations by year
2026: 14 · 2025: 11 · 2024: 11 · 2023: 16 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 15 · 2016: 10 · 2015: 15 · 2014: 24 · 2013: 14 · 2012: 2
FWCI
8.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Australian National Health and Medical Research Council (571281, 512657)
  • CSL Limited
  • Australian Food and Grocery Council
  • Bupa Australia
  • Johnson and Johnson
  • Merck Schering Plough
  • Roche
  • Servier
  • United Healthcare Group
  • Roche Diagnostics
  • Solvay
  • Abbott
  • Merck
  • sanofi-aventis
  • Baxter
  • Gambro
  • Novartis
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
fibrates, chronic kidney disease, lipid profile, triglycerides, cholesterol, albuminuria, serum creatinine, estimated glomerular filtration rate
MeSH terms
Cardiovascular Diseases, Humans, Kidney Function Tests, Lipids, Risk Factors, Treatment Outcome, Disease Progression

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-19.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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