Efficacy of short-term high-dose statin pretreatment in prevention of contrast-induced acute kidney injury: updated study-level meta-analysis of 13 randomized controlled trials.

Joo Myung Lee,Ji-Hyun Jung,Kyung Woo Park,Jung-Kyu Han,Sang-Ho Jo,Hyun-Jae Kang,Han-Mo Yang,Ki-Hyun Jeon,Sang Eun Lee,Hack-Lyoung Kim,Bon-Kwon Koo,Hyo-Soo Kim,Jonghanne Park,Giuseppe Remuzzi

doi:10.1371/journal.pone.0111397

Abstract

BackgroundThere have been conflicting results across the trials that evaluated prophylactic efficacy of short-term high-dose statin pre-treatment for prevention of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary angiography (CAG). The aim of the study was to perform an up-to-date meta-analysis regarding the efficacy of high-dose statin pre-treatment in preventing CIAKI.Methods and ResultsRandomized-controlled trials comparing high-dose statin versus low-dose statin or placebo pre-treatment for prevention of CIAKI in patients undergoing CAG were included. The primary endpoint was the incidence of CIAKI within 2–5days after CAG. The relative risk (RR) with 95% CI was the effect measure. This analysis included 13 RCTs with 5,825 total patients; about half of them (n = 2,889) were pre-treated with high-dose statin (at least 40 mg of atorvastatin) before CAG, and the remainders (n = 2,936) pretreated with low-dose statin or placebo. In random-effects model, high-dose statin pre-treatment significantly reduced the incidence of CIAKI (RR 0.45, 95% CI 0.35–0.57, p<0.001, I2 = 8.2%, NNT 16), compared with low-dose statin or placebo. The benefit of high-dose statin was consistent in both comparisons with low-dose statin (RR 0.47, 95% CI 0.34–0.65, p<0.001, I2 = 28.4%, NNT 19) or placebo (RR 0.34, 95% CI 0.21–0.58, p<0.001, I2 = 0.0%, NNT 16). In addition, high-dose statin showed significant reduction of CIAKI across various subgroups of chronic kidney disease, acute coronary syndrome, and old age (≥60years), regardless of osmolality of contrast or administration of N-acetylcystein.ConclusionsHigh-dose statin pre-treatment significantly reduced overall incidence of CIAKI in patients undergoing CAG, and emerges as an effective prophylactic measure to prevent CIAKI.

Highlights

Contrast-induced acute kidney injury (CIAKI) is a wellrecognized complication of coronary angiography (CAG) with iodinated contrast medium and is the third leading cause of hospital-acquired acute renal failure
[4] none of the agents were proved to be effective in preventing contrast-induced acute kidney injury (CIAKI). [4,5] Currently, recommendations of the European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) or the ACCF/AHA/ SCAI guideline are limited to the prophylactic intravenous hydration, use of iso- or low-osmolar contrast agents, and reduced dosages of contrast agents to prevent occurrence of CIAKI. [6,7] Since a few observational studies suggested that 3-hydroxyl-3methylglutaryl coenzyme A reductase inhibitors may reduce CIAKI incidence, several RCTs have evaluated the potential benefit of statin in prevention of CIAKI. [8,9]Statin’s postulated mechanism of kidney protection was through its pleotropic effects, i.e. antioxidant, anti-inflammatory, and antithrombotic actions
24 studies were retrieved for detailed evaluation, of which 13 RCTs met inclusion criteria (Figure 1). [11,12,13,14,15,21,22,23,24,25,26,27,28] These 13 RCTs included a total of 5,825 adult patients, 2,889 (49.6%) of which were allocated to the high-dose statin group and 2,936 (50.4%) of which were allocated to the control group

Summary

Introduction

Contrast-induced acute kidney injury (CIAKI) is a wellrecognized complication of coronary angiography (CAG) with iodinated contrast medium and is the third leading cause of hospital-acquired acute renal failure. [8,9]Statin’s postulated mechanism of kidney protection was through its pleotropic effects, i.e. antioxidant, anti-inflammatory, and antithrombotic actions These previous RCTs and metaanalysis of high-dose statin pre-treatment showed disappointing results. [10,11,12] Recently, three RCTs with relatively large sample size (NAPLES II, PRATO-ACS, TRACK-D trial) have reported promising results favoring prophylactic efficacy of high-dose statin in prevention of CIAKI. There have been conflicting results across the trials that evaluated prophylactic efficacy of short-term highdose statin pre-treatment for prevention of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary angiography (CAG).

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