|Year : 2018 | Volume
| Issue : 3 | Page : 894-899
Efficacy of high-dose atorvastatin in preventing contrast-induced nephropathy in patients undergoing coronary angiography
Saied Shalaby, Awny Gamal, Osama R Kandeel
Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||18-Mar-2017|
|Date of Acceptance||07-May-2017|
|Date of Web Publication||31-Dec-2018|
Osama R Kandeel
Department of Cardiology, Faculty of Medicine, Menoufia University, Kamshish, Tala, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study was to examine the efficacy of high-dose atorvastatin in preventing contrast-induced nephropathy (CIN) in statin-naive patients with moderate or high risk of CIN undergoing coronary angiography.
CIN occurs in 20–30% of patients who receive standard preventive measures. This means that current treatments are not adequate.
Patients and methods
The present study included 300 patients scheduled for coronary angiography. They were randomized into two groups: the atorvastatin group received 80-mg atorvastatin 12 h before the procedure, with a further 40-mg preprocedural dose, and the placebo group did not receive the loading dose of atorvastatin. The primary end point of the study was evaluation of renal function before and 48 h after contrast-medium administration.
A total of 300 patients were included in this study. The incidence of nephropathy in the placebo group was 20% (30 patients), whereas the incidence in the atorvastatin group was 9.3% (14 patients) (P = 0.009).
High-dose atorvastatin has a significant protective role against contrast-induced nephropathy in patients with moderate and high risk for contrast nephropathy undergoing coronary angiography.
Keywords: atorvastatin, coronary angiography, kidney diseases
|How to cite this article:|
Shalaby S, Gamal A, Kandeel OR. Efficacy of high-dose atorvastatin in preventing contrast-induced nephropathy in patients undergoing coronary angiography. Menoufia Med J 2018;31:894-9
|How to cite this URL:|
Shalaby S, Gamal A, Kandeel OR. Efficacy of high-dose atorvastatin in preventing contrast-induced nephropathy in patients undergoing coronary angiography. Menoufia Med J [serial online] 2018 [cited 2020 Apr 8];31:894-9. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/894/248731
| Introduction|| |
Contrast-induced nephropathy (CIN) is defined as an increase of more than 25% or more than 0.5 mg/dl (44 μmol/l) of serum creatinine from baseline within 48 − 72 h following intravenous injection of contrast material if other etiologies of renal impairment can be excluded, usually peaking on the third to fifth day, and returning to baseline values within 10–14 days.
The overall incidence of CIN in the general population has been estimated to be 1–6%. The incidence is higher in patients undergoing percutaneous coronary intervention (PCI) leading to increased mortality, morbidity, and in-hospital stay. In their retrospective analysis of the Mayo Clinic PCI registry comprising 7586 patients, Rihal et al. found that the incidence of CIN was 3.3% and dialysis was required in 0.3% of cases.
A variety of preventive measures have been used to protect patients against CIN,. Hydration with normal saline is the most widely accepted preventive measure,. However, CIN may develop in 3–25% of patients despite appropriate hydration,. This means that current treatments are not enough, and the optimal strategy to prevent CIN has not been established.
Statins exert a number of pleiotropic effects including enhancement of endothelial function, stabilization of atherosclerotic plaques, decrease in oxidative stress and inflammation, and inhibition of thrombogenic response.
Thus, our study aimed to examine the efficacy of high-dose atorvastatin in preventing CIN in statin-naive patients with moderate or high risk for CIN undergoing coronary angiography.
| Patients and Methods|| |
This study was designed as a cross-sectional, observational study.
Patients presenting with suspected or diagnosed coronary artery disease for elective coronary angiography, with moderate or high risk for CIN based on the Mehran score, were included.
The present study was approved by the local Ethics Committee, and informed consent was obtained from all participants.
The present study included 300 patients. After careful history taking, general examination, and echocardiographic assessment of ejection fraction, participants were randomized them into two groups: the atorvastatin group (n = 150) received 80-mg atorvastatin, 12 h before the procedure, with a further 40 mg preprocedural dose, and the placebo group (n = 150) did not receive the loading dose of atorvastatin. Both groups received N-acetylcysteine (600 mg twice daily) on the day before and the day of administering contrast media and adequate hydration with 1 ml/kg/h. Normal saline was administered 12 h before the procedure and up to 12 h after the procedure.
Before the procedure and 2 days after the procedure, blood samples were obtained for measuring creatinine and creatinine clearance (CrCl). Patients considered as having CIN had serum creatinine and CrCl rechecked 2 weeks after the procedure.
The collected data were organized, tabulated, and statistically analyzed using statistical package for the social sciences (SPSS, version 19) created by IBM (Chicago, Illinois, USA). For numerical values, the ranges, means, and SDs were calculated. The differences between two mean values were used with Student's t test. Differences in mean values before and after intervention were tested using paired t test. For categorical variables, numbers and percentages were calculated, and differences between subcategories were tested using the χ2 test. The level of significance was set at P value less than 0.05.
| Results|| |
The baseline characteristics of both groups showed that there was no statistically significant difference between both groups regarding age and sex distribution, BMI, ejection fraction assessed by echocardiography, and the amount of contrast injected. The mean age of the placebo group was 55.32 ± 12.93, and the mean age of the atorvastatin group was 54.45 ± 12.99 (P = 0.56). Among all, 159 patients were males representing 53% of the study population and the remainder 141 patients were females representing 47% of the study population. The placebo group included 81 (54%) males and 69 (46%) females. The atorvastatin group included 78 (52%) males and 72 (48%) females (P = 0.73). In addition, there was no statistically significant difference between both groups regarding risk factors of CIN including diabetes mellitus, hypertension, congestive heart failure, impaired kidney function, and anemia as shown in [Table 1].
|Table 1: Distribution of patients regarding age, sex, body mass index, and risk factors in both groups|
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By comparing the preprocedural and postprocedural kidney functions between both groups we found that there was no significant difference regarding baseline kidney functions (preprocedural serum creatinine was 0.96 ± 0.26 mg/dl in the placebo group vs. 0.95 ± 0.24 mg/dl in the atorvastatin group with a P = 0.9, and the preprocedural CrCl was 93.72 ± 20.95 in the placebo group vs. 95 ± 17.91 in the atorvastatin group with a P = 0.92) [Figure 1] and [Figure 2]. Although there was significant difference regarding postprocedural kidney functions (postprocedural serum creatinine was 1.09 ± 0.47 mg/dl in the placebo group vs. 1.01 ± 0.43 mg/dl in the atorvastatin group with a P = 0.03, and postprocedural CrCl was 87.17 ± 27.27 in the placebo group vs. 95.39 ± 28.22 in the atorvastatin group with a P = 0.004) [Figure 3] and [Figure 4].
By comparing preprocedural and postprocedural kidney functions in each group we found that there was no significant difference in the atorvastatin group with a mean preprocedural value of serum creatinine of 0.95 mg/dl and postprocedural value of 1.01 mg/dl (P = 0.15), and a mean preprocedural value of CrCl of 95 ml/min and postprocedural value of 95.35 ml/min (P = 0.087). However, there was a statistically significant difference in the placebo group with a mean preprocedural serum creatinine value of 0.96 mg/dl and postprocedural value of 1.09 mg/dl (P = 0.003). The mean preprocedural CrCl value was 93.72 ml/min and the postprocedural value was 87.17 ml/min (P = 0.002) [Table 2].
|Table 2: Comparison between preprocedural and postprocedural creatinine and creatinine clearance in both groups|
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Of the whole study population, 44 (14.7%) patients developed CIN. Thirty (20%) of them were included in the placebo group, whereas 14 (9.3%) patients were included in the atorvastatin group with a statistically significant difference (P = 0.009) [Table 3].
|Table 3: Distribution of participants regarding contrast-induced nephropathy in both groups|
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We noticed that the incidence of CIN among high-risk patients was 61.1% in the placebo group (22 patients from 36) and 25% in the atorvastatin group (eight patients from 32) with a statistically significant difference (P = 0.03), indicating that atorvastatin has a protective effect against CIN in high-risk groups.
However, the incidence of CIN among moderate-risk patients was 7% in the placebo group (eight patients from 114) and 5.1% in the atorvastatin group (six patients from 118), with no statistically significant difference (P = 0.59), indicating that atorvastatin has no significant protective effect against CIN in the moderate-risk group, but there was a trend toward decreasing incidence of CIN.
By analyzing the incidence of CIN in both groups in relation to each risk factor, we found that the incidence of CIN among diabetics in the placebo group was 25% (27 patients out of 108), whereas the incidence in the atorvastatin group was 11.4% (13 patients out of 114) with a P value is equal to 0.008. The incidence of CIN among hypertensives in the placebo group was 26.8% (22 patients out of 82), whereas the incidence in the atorvastatin group was 9.6% (eight patients out of 83) with a P value equal to 0.007. The incidence of CIN among those with congestive heart failure in the placebo group was 26.8% (22 patients out of 82), whereas the incidence in the atorvastatin group was 14.8% (12 patients out of 81), with no statistically significant difference (P = 0.06). However, there was a trend toward higher incidence in the placebo group. The incidence of CIN among those with baseline impaired kidney function in the placebo group was 40% (12 patients out of 30), whereas the incidence in the atorvastatin group was 14.8% (four patients out of 27), with a P value equal to 0.03. The incidence of CIN among those with anemia in the placebo group was 26.7% (16 patients out of 60), whereas the incidence among those with anemia in the atorvastatin group was 13.7% (seven patients out of 51), with no statistically significant difference (P = 0.09). However, there was a trend toward higher incidences in the placebo group [Table 4].
|Table 4: Distribution of risk factors regarding contrast-induced nephropathy incidence|
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| Discussion|| |
Statins may be effective in decreasing the incidence of CIN as evaluated in several observational studies, and randomized controlled trials,.
Our study aimed to evaluate the efficacy of high-dose atorvastatin in preventing CIN in statin-naive patients, with moderate and high risk for CIN, undergoing elective coronary angiography.
The incidence of CIN in our study population was 14.7% (44 out of 300 patients). The incidence of CIN in the placebo group was 20% (30 out of 150 patients), whereas the incidence of CIN in the atorvastatin group was 9.3% (14 out of 150 patients) (P = 0.009).
The overall incidence of CIN in this study was relatively high. This can be explained by the high-risk profile of recruited patients: 74% (222) of patients had diabetes mellitus, 55% (165) of patients had hypertension, 54.3% (163) of patients had heart failure, 40% (120) of patients had anemia, and 19% (57) of patients had baseline impaired kidney function. On the basis of the risk score introduced by Mehran et al., ∼77.3% of patients were at medium risk for the development of CIN, whereas 22.7% of patients were at high risk for the development of CIN.
In our study, there was a statistically significant difference between preprocedural and postprocedural renal functions in the placebo group with a P value equal to 0.003 for mean serum creatinine and 0.002 for mean CrCl. The difference was not significant in the atorvastatin group with a P value equal to 0.15 for mean serum creatinine and 0.87 for mean CrCl, which means that a high loading dose of atorvastatin prevents significant increase in serum creatinine and significant decrease in CrCl that occurs with contrast-medium administration.
Patti et al., in ARMYDA-CIN, evaluated whether short-term high-dose atorvastatin reduces the incidence of CIN after PCI. Accordingly, statin-naive patients with acute coronary syndrome undergoing PCI (n = 241) randomly received atorvastatin [80 mg 12 h before intervention with another 40-mg preprocedural dose (n = 120) or placebo (n = 121)]. Only 5% of patients in the atorvastatin group developed CIN versus 13.2% in the placebo group (P = 0.046).
In the study by Patti et al., there was a significant difference between the atorvastatin group and the placebo group regarding CIN incidence. However, our study investigated the efficacy of the short-term high-dose atorvastatin load in statin-naive patients undergoing elective coronary angiography, and accordingly the incidence of CIN was much lower in the atorvastatin group than in the placebo group (9.3% out of 150 patients vs. 20% out of 150 patients) with higher statistically significant difference (P = 0.009).
The protective effect of atorvastatin is contributed mainly to the pleiotropic effects acting at different stages of CIN mechanisms including downregulation of angiotensin receptors, reducing endothelin production, increasing nitric oxide bioavailability, attenuating inflammation, limiting reactive oxygen species synthesis, and preventing complement-mediated injury.
Acikel et al. evaluated the effects of two different statin therapy regimens, short-term statin therapy (atorvastatin beginning 3 days before contrast exposure) and long-term statin therapy on the occurrence of CIN following elective coronary angiography.
In that study, patients were divided into three groups, one group of 80 patients received short-term statin therapy (40 mg/day started 3 days before coronary angiography), a second group of 80 patients were included as controls, and a third group of 80 patients received long-term statin therapy.
They found that both short-term and long-term statin therapy groups had better postprocedure renal function parameters compared with the control group. In addition, no differences were detected between both statin regimens, suggesting that similar renal protection was achieved in both statin groups, regardless of the length of statin treatment before coronary angiography.
The results of this study showed that the efficacy of a high loading dose of atorvastatin is not significant in patients already on chronic statin therapy, as the there is no difference between both regimens – short-term statin therapy and long-term statin therapy.
| Conclusion|| |
From our study, we concluded that short-term high-dose atorvastatin before coronary angiography in statin-naive patients can decrease the incidence of CIN in patients with moderate and high risk for CIN based on the Mehran score.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Schilp J, de Blok C, Langelaan M, Spreeuwenberg P, Wagner C. Guideline adherence for identification and hydration of high-risk hospital patients for contrast-induced nephropathy. BMC Nephrol 2014; 15
Owen, RJ, Hiremath, S, Myers, A, Fraser-Hill M, Barrett BJ. Canadian Association of Radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012. Can Assoc Radiol J 2014; 65
Parfrey P. The clinical epidemiology of contrast-induced nephropathy. Cardiovasc Intervent Radiol 2005; 28 (Suppl 2):
Leon MB, Piazza N, Nikolsky E, Blackstone EH, Cutlip D, Kappetein AP, et al.
Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. Eur Heart J 2011; 32
Rihal, CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, et al.
Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002; 105
Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, et al.
Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004; 291
Stacul F, Adam A, Becker CR, Davidson C, Lameire N, McCullough PA, et al.
CIN Consensus Working Panel: strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol 2006; 98
Rudnick MR, Kesselheim A, Goldfarb S. Contrast-induced nephropathy: how it develops, how to prevent it. Cleve Clin J Med 2006; 73
Au TH, Bruckner A, Mohiuddin SM, Hilleman DE. The prevention of contrast-induced nephropathy. Ann Pharmacother 2014; 48
Masuda M, Yamada T, Mine T, Morita T, Tamaki S, Tsukamoto Y, et al.
Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure. Am J Cardiol 2007; 100
Haller C, Hizoh I. The cytotoxicity of iodinated radio contrast agents on renal cells in vitro
. Invest Radiol 2004; 39
Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, et al.
Asimple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol 2004; 44
Khanal S, Attallah N, Smith DE, Kline-Rogers E, Share D, O'Donnell MJ, et al.
Statin therapy reduces contrast-induced nephropathy: an analysis of contemporary percutaneous interventions. Am J Med 2005; 118
Patti G, Nusca A, Chello M, Pasceri V, D'Ambrosio A, Vetrovec GW, et al.
Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention. Am J Cardiol 2008; 101
Jo SH, Koo BK, Park JS, Kang HJ, Cho YS, Kim YJ, et al.
Prevention of radio contrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial – a randomized controlled study. Am Heart J 2008; 155
Kandula P, Shah R, Singh N, Markwell SJ, Bhensdadia N, Navaneethan SD. Statins for prevention of contrast-induced nephropathy in patients undergoing non-emergent percutaneous coronary intervention. Nephrology (Carlton) 2010; 15
Patti G, Ricottini E, Nusca A, Colonna G, Pasceri V, D'Ambrosio A, et al.
Short-term, high-dose atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [atorvastatin for reduction of myocardial damage during angioplasty – Contrast-induced nephropathy] trial. Am J Cardiol 2011; 108
Ichiki T, Takeda K, Tokunou T, Iino N, Egashira K, Shimokawa H et al.
Down regulation of angiotensin II type 1 receptor by hydrophobic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2001; 21
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45
Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond lipid lowering – Are they clinically relevant?. Eur Heart J 2003; 24
Rikitake Y, Kawashima S, Takeshita S, Yamashita T, Azumi H, Yasuhara M, et al.
Anti-oxidative properties of fluvastatin, an HMG CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 2001; 154
Mason JC, Ahmed Z, Mankoff R, Lidington EA, Ahmad S, Bhatia V, et al.
Statin-induced expression of decay-accelerating factor protects vascular endothelium against complement-Mediated injury. Circ Res2002; 91
Acikel S, Muderrisoglu H, Yildirir A, Aydinalp A, Sade E, Bayraktar N, et al.
Prevention of contrast-induced impairment of renal function by short-term or long-term statin therapy in patients undergoing elective coronary angiography. Blood Coagul Fibrinolysis 2010; 21
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]