High-Dose Statin Pretreatment for the Prevention of Contrast-Induced Nephropathy: A Meta-analysis

doi:10.1016/j.cjca.2011.05.005

Canadian Journal of Cardiology

Volume 27, Issue 6, November–December 2011, Pages 851-858

https://doi.org/10.1016/j.cjca.2011.05.005 Get rights and content

Abstract

Background

Contrast-induced nephropathy (CIN) is a rare but serious complication following contrast-based procedures. Statins have been postulated to prevent CIN via various mechanisms. However, the outcomes following statin administration to prevent CIN have been inconsistent.

Methods

A meta-analysis of published randomized clinical trials was performed to determine if short-term administration of high-dose statin is superior to conventional-dose statin or placebo among patients undergoing catheterization and interventional procedures in preventing CIN.

Results

Data were combined across 8 published clinical trials in which 1423 patients were identified. Pooled analyses showed that short-term high-dose statin treatment can decrease the occurrence of CIN (risk ratio 0.51, 95% confidence interval [CI], 0.34-0.77; P = 0.001) and 48-hour serum creatinine level (standardized mean difference [SMD] –0.07 mg/dL; 95% CI, –0.11 to –0.04 mg/dL; P < 0.00001). However, subgroup analysis showed that statin pretreatment cannot decrease the occurrence of CIN in patients with preexisting renal impairment (RR 0.90; 95% CI, 0.49-1.65; P = 0.73). No evidence of publication bias was detected.

Conclusions

This meta-analysis supports the effectiveness of short-term high-dose statin pretreatment for both decreasing the level of serum creatinine and reducing the rate of CIN in patients undergoing diagnostic and interventional procedures requiring contrast media. However, prospective clinical trials will be needed to draw a definitive conclusion in this area.

Résumé

Introduction

La néphropathie induite par les produits de contraste (NIC) est une complication rare, mais sérieuse, à la suite d'examens de contraste. Les statines sont présumées prévenir la NIC par divers mécanismes. Cependant, les résultats suivant l'administration de statines pour prévenir la NIC ont été inconsistants.

Méthodes

Une métaanalyse d'essais cliniques aléatoires publiés a été faite pour déterminer si l'administration à court terme de doses élevées de statines est supérieure à la dose usuelle de statines ou au placebo chez les patients subissant une cathétérisation et des procédures interventionnelles en prévention de la NIC.

Résultats

Les données ont été combinées à partir de 8 essais cliniques publiés parmi lesquels 1 423 patients ont été identifiés. Les analyses groupées ont montré qu'un traitement à court terme à doses élevées de statines peut diminuer l'occurrence de la NIC (risque relatif [RR] de 0,51, intervalle de confiance [IC] de 95 %, 0,34-0,77; P = 0,001) et le niveau de créatinine sérique après 48 heures (déviation standard moyenne [DMS]) –0,07 mg/dl; IC de 95 %, –0,11 à –0,04 mg/dl; P < 0,00001). Cependant, l'analyse par sous-groupe a montré qu'un prétraitement par statines ne peut pas diminuer l'occurrence de la NIC chez les patients avec une insuffisance rénale préexistante (RR de 0,90; IC de 95 %, 0,49-1,65; P = 0,73). Aucune preuve de biais de publication n'a été trouvée.

Conclusions

Cette métaanalyse appuie l'efficacité d'un prétraitement à court terme à doses élevées de statines tant pour la diminution du niveau de créatinine sérique que pour la réduction du taux de NIC chez les patients subissant un diagnostic et des procédures interventionnelles nécessitant un produit de contraste. Cependant, des essais cliniques prospectifs seront nécessaires pour tirer une conclusion définitive dans ce domaine.

Section snippets

Materials and Methods

Our prespecified inclusion criteria were as follows: the subjects were adults; the reports were in the English or Chinese language literature; high-dose statins a priori (defined as a daily dose of 80 mg or 40 mg12, 13) were administered; periprocedural administration was described as immediately preceding or within 24 hours of the planned contrast exposure; prospective trials were of individuals randomized to statin, administered orally, vs a control group; and trials included the incidence of

Description of studies

Of the 67 potentially relevant reports initially screened, a total of 8 trials were identified.7, 8, 9, 10, 11, 15, 16, 17 Eight trials with a total of 1423 patients (695 assigned to high-dose statin and 728 assigned to the control arm) were included, and the relevant data extracted. The characteristics of included trials are described in Table 1, Table 2, Table 3, Table 4. Five trials in English and 3 trials in Chinese were retrieved with full text of journal articles. The subject population

Discussion

The present meta-analysis based on currently available published randomized clinical trials demonstrates that the administration of high-dose statin pretreatment is superior to low-dose statin or placebo in preventing CIN among patients undergoing diagnostic and interventional procedures requiring contrast media. In addition, short-term prophylaxis with high-dose statin therapy tended to be associated with reduction in serum creatinine after coronary artery angiography. However, subgroup

Conclusions

The present analysis suggests that statins at individual periprocedural doses 80 mg or 40 mg per day decrease the incidence of CIN (none of the trials reported significant side effects). Further prospective studies are needed to better understand the value of high-dose statins in protecting against CIN.

Disclosures

The authors have no conflicts of interest to disclose.

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Contrast-induced nephropathy (CIN) is reversible acute renal failure observed following administration of iodinated contrast media (CM) during angiographic or other medical procedures such as urography. There are various mechanisms through which CM develop their nephrotoxic effects, including oxidative stress and apoptosis. CIN is a real-life, albeit not very rare, entity. Exact pathophysiology remains obscure and no standard diagnostic criteria apply. The Acute Kidney Injury Network criteria was recently employed but its incidence/clinical significance warrants further clarification based on recent methodological advancements, because most published studies to date were contaminated by bias. The current study is a comprehensive review conducted to provide an overview of the basic concepts of CIN and summarize recent knowledge on its pathophysiology and the evidence supporting potential prevention strategies. CIN is expected to increase morbidity, hospital stay and mortality, while all patients scheduled to receive CM should undergo risk assessment for CIN and high-risk patients may be considered candidates for prevention strategies. The value of using compounds with antioxidant properties other than sodium bicarbonate, remains controversial, warranting further clinical investigation.
Comparative Effectiveness of 12 Treatment Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-analysis
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Citation Excerpt :
Pre-existing decreased kidney function is an independent predictor of contrast-induced AKI.41 Findings from some previous pairwise meta-analyses35,36 suggested that statin use may not be effective for patients with pre-existing chronic kidney disease. Our metaregression analyses found that baseline serum creatinine concentration as a continuous covariate is not a statistically significant effect modifier (regression coefficient, 0.09; 95% credible intervals, −1.86 to 1.90).
To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI).
Systematic review containing a Bayesian network meta-analysis of randomized controlled trials.
Participants undergoing diagnostic and/or interventional procedures with contrast media.
Randomized controlled trials comparing the active drug treatments with each other or with hydration alone.
Any of the following drugs in combination with hydration: N-acetylcysteine (NAC), theophylline (aminophylline), fenoldopam, iloprost, alprostadil, prostaglandin E₁, statins, statins plus NAC, bicarbonate sodium, bicarbonate sodium plus NAC, ascorbic acid (vitamin C), tocopherol (vitamin E), α-lipoic acid, atrial natriuretic peptide, B-type natriuretic peptide, and carperitide.
The occurrence of contrast-induced AKI.
The trial network included 150 trials with 31,631 participants and 4,182 contrast-induced AKI events assessing 12 different interventions. Compared to hydration, ORs (95% credible intervals) for contrast-induced AKI were 0.31 (0.14-0.60) for high-dose statin plus NAC, 0.37 (0.19-0.64) for high-dose statin alone, 0.37 (0.17-0.72) for prostaglandins, 0.48 (0.26-0.82) for theophylline, 0.62 (0.40-0.88) for bicarbonate sodium plus NAC, 0.67 (0.54-0.81) for NAC alone, 0.64 (0.41-0.95) for vitamins and analogues, 0.70 (0.29-1.37) for natriuretic peptides, 0.69 (0.31-1.37) for fenoldopam, 0.78 (0.59-1.01) for bicarbonate sodium, and 0.98 (0.41-2.07) for low-dose statin. High-dose statin plus NAC or high-dose statin alone were likely to be ranked the best or the second best for preventing contrast-induced AKI. The overall results were not materially changed in metaregressions or subgroup and sensitivity analyses.
Patient-level data were unavailable; unable to include some treatment agents; low event rates; imbalanced distribution of participants among treatment strategies.
High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced AKI in patients undergoing diagnostic and/or interventional procedures requiring contrast media.
Contrast-induced nephropathy: An update
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Contrast-induced nephropathy (CIN) is common in hospitalized patients. Its occurrence is associated with an increased hospitalization stay and cost, morbidity and mortality. Thus, preventives strategies remain a major issue. Patients that are referred for cardiac catheterization are among the most vulnerable to develop CIN due to their comorbidities. Moreover, in some cases, such preventives measures cannot be introduced due to emergent clinical settings. After a summary regarding the properties of iodinated contrast medium, the aim of this work was to review the definition, pathophysiology, diagnosis and preventive strategies related to CIN.

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Systematic review/meta-analysisHigh-Dose Statin Pretreatment for the Prevention of Contrast-Induced Nephropathy: A Meta-analysis

Abstract

Background

Methods

Results

Conclusions

Résumé

Introduction

Méthodes

Résultats

Conclusions

Section snippets

Materials and Methods

Description of studies

Discussion

Conclusions

Disclosures

Am J Med

Am J Cardiol

Am J Cardiol

Am Heart J

J Clin Epidemiol

Control Clin Trials

Pharmacol Ther

Kidney Int

J Cardiol

Can J Cardiol

Contrast-induced acute kidney injury

Circulation

Contrast-induced nephropathy in patients undergoing computed tomography (CONNECT): a clinical problem in daily practice?A multicenter observational study

Acta Radiol

Contrast-induced nephropathy and its prevention: what do we really know from evidence-based findings?

J Nephrol

Systematic review/meta-analysis
High-Dose Statin Pretreatment for the Prevention of Contrast-Induced Nephropathy: A Meta-analysis