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Effect of statins on contrast-induced nephropathy in patients with acute myocardial infarction treated with primary angioplasty
International Journal of Cardiology 126 (2008) 435 – 436 www.elsevier.com/locate/ijcard
Letter to the Editor
Effect of statins on contrast-induced nephropathy in patients with acute myocardial infarction treated with primary angioplasty ☆ Jing-Lin Zhao, Yue-Jin Yang ⁎, Yuan-hui Zhang, Shi-Jie You, Yong-Jian Wu, Run-Lin Gao Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Li Shi Road 167, Xi-Cheng District, Beijing, 100037, China Received 31 December 2006; accepted 5 January 2007 Available online 25 April 2007
Abstract We investigated whether pretreatment with statin may prevent contrast-induced nephropathy in patients who underwent primary coronary intervention for acute myocardial infarction (AMI). A total of 279 consecutive patients who underwent successful primary angioplasty for a first AMI were studied. Contrast-induced nephropathy was defined as an increase in serum creatinine of ≥ 5 mg/dL after the primary PCI. 56 patients receiving statin treatment before admission had lower incidence of the contrast-induced nephropathy than those without it (7.1% and 20.6%, P b 0.01). Multivariable logistic regression analysis revealed that absence of statin pre-treatment was a significant predictor of the reperfusion arrhythmia along with anterior AMI, baseline creatinine value, time-to-reperfusion, higher volume of the contrast agent. Pretreatment with statin could reduce the contrast-induced nephropathy after primary coronary intervention in patients with AMI. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Myocardial infarction; Reperfusion; Statin
Contrast-induced nephropathy (CIN) is a complication of coronary diagnostic and interventional procedures. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to have beneficial effect on renal function [1]. However, little is known about the effect of pretreatment with statins on contrast-induced nephropathy in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). Therefore, in the present study, we investigated whether the statin treatment before the onset of acute myocardial infarction could reduce the CIN in patients who underwent primary coronary intervention. 1. Methods We studied 279 consecutive patients who underwent primary angioplasty for a first AMI between September 2001
and January 2005. Contrast-induced nephropathy was defined as an increase in serum creatinine of ≥ 0.5 mg/dL after the primary PCI. All patients received aspirin (300 mg) plus clopidigrel (300 mg) orally before coronary angiography. Coronary angiography was performed using the right femoral approach to determine culprit lesion and collateral channels. We performed coronary intervention with angioplasty and implanted a stent to reduce the residual diameter stenosis to b50%. Continuous variables were compared by one-way ANOVA. Comparisons of categorical variables were performed with the Fisher's exact test. Univariable and multivariable logistic regression analyses were used to identify independent predictors for the contrast-induced nephropathy. A value of P b 0.05 (2-sided) was considered statistically significant. 2. Results
☆
Supported, in part, by a grant-in-aid (30572439) from the National Natural Science Foundation of China. ⁎ Corresponding author. Tel.: +86 10 88398080. E-mail address: [email protected] (Y.-J. Yang). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.01.123
56 patients had chronically received statin before admission: 23 patients had received pravastatin (20–40 mg/day), 21 patients simvastatin (20–40 mg/day), and 12 patients
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J.-L. Zhao et al. / International Journal of Cardiology 126 (2008) 435–436
Table 1 Clinical characteristics of patients with or without statin
Creatinine on admission (mg/dl) CIN, n (%) Total cholesterol (mg/dl) Triglycerides (mg/dl) Symptom onset-reflow time (h) EF on admission (%) SBP (mm Hg) Anterior wall infarction, n (%) Contrast volume (ml) Medication before AMI ACEI pre-treatment, n (%) β-Blocker pre-treatment, n (%) Aspirin pre-treatment, n (%)
With statin n = 56
Without statin n = 223
Pvalue
1.11 ± 0.3
1.09 ± 0.2
4 (7.1) 198 ± 43 107 ± 98 5.6 ± 4.3
46(20.6) 196 ± 52 101 ± 78 5.9 ± 5.2
47 ± 17 131 ± 31 38 (67.8)
48 ± 14 136 ± 26 148 (66.4)
0.36 0.41 0.79
336 ± 165
358 ± 223
0.26
12 (21.4)
48 (21.5)
0.91
6 (10.7)
19 (8.5)
0.12
18 (32.1)
78 (34.9)
0.89
0.18 − 0.05 0.47 0.56 0.41
⁎P values for the differences between the patients with or without statin. Data are presented as the mean value ± S.D. or number or percentage of patients. CIN, EF and SBP represent contrast-induced nephropathy, ejection fraction and systolic blood pressure respectively.
atrovastatin (10–20 mg/day). The 50 patients (17.9%) showed the contrast-induced nephropathy. These 50 patients were allocated to the contrast-induced nephropathy group, and the remaining 229 patients to the non-contrast-induced nephropathy group. The patients with the contrast-induced nephropathy had high incidence of anterior AMI, higher baseline creatinine value, longer time-to-reperfusion, lower left ventricular ejection fraction, and higher volume of the contrast agent during PCI than those without contrast-induced nephropathy. Number of the patients pretreated with statin was significantly lower in the contrast-induced nephropathy group than in the non-contrast-induced nephropathy group (8% vs 22.7%, P b 0.01). The incidence of contrast-induced nephropathy was significantly lower in patients with statin than in those without it (7.1% and 20.6%; P b 0.01). Statin pre-treatment was an independent predictor of the contrast-induced nephropathy along with anterior AMI, baseline creatinine value, time-toreperfusion, higher volume of the contrast agent (Table 1). 3. Discussion The present study demonstrated that the patients receiving statin pre-treatment had lower incidence of the contrast-
induced nephropathy than those without statin. Multivariable logistic analysis revealed that statin pre-treatment was an independent predictor for the contrast-induced nephropathy. The results indicated that statin could reduce contrastinduced nephropathy in patients undergoing primary PCI. To our knowledge, this is the first published report of statin pretreatment associated with reduction in contrast-induced nephropathy in patients with AMI. The exact mechanism of contrast-induced nephropathy is not known. Oxidation injury, vasoconstriction, injury from chemokines, tubular obstruction, mitochondrial injury, and plasma membrane toxicity have been implicated [2]. The patients with AMI treated with primary PCI represent a population at higher risk for contrast-induced nephropathy than those undergoing elective PCI. Several conditions may contribute to renal injury in this setting. Among them, hypotension or even shock, a large volume of contrast media, and the impossibility of starting a renal prophylactic therapy are the factors most likely involved. The precise mechanism, by which statin is beneficial in the reduction of the contrastinduced nephropathy, remains unclear. Its effects, including stabilization of vulnerable plaque, amelioration of endothelial dysfunction and inhibition of neutrophils [3], may provide some explanations. In addition, statin reduces ischemic and angiotensin-II-mediated acute renal failure [4]. These pleiotropic effects could contribute to the preventive effect of statin on contrast-induced nephropathy. In summary, pre-treatment with statin could reduce the contrast-induced nephropathy after primary coronary intervention in patients with AMI. References [1] Schouten O, Kok NF, Boersma E. Effects of statins on renal function after aortic cross clamping during major vascular surgery. Am J Cardiol 2006;97:1383–5. [2] Weisberg LS, Kurnik PB, Kurnik BR. Radiocontrast-induced nephropathy in humans role for vasoconstriction. Kidney Int 1992;41:1408–15. [3] Wan MX, Schramm R, Klintman D, et al. A statin-based inhibitor of lymphocyte function antigen-1 protects against ischemia/reperfusioninduced leukocyte adhesion in the colon. Br J Pharmacol 2003;140: 395–401. [4] Park JK, Muller DN, Mervaala EM, et al. Cerivastatin prevents angiotensin II-induced renal injury independent of blood pressure- and cholesterol-lowering effects. Kidney Int 2000;58:1420–30.
Letter to the Editor
Effect of statins on contrast-induced nephropathy in patients with acute myocardial infarction treated with primary angioplasty ☆ Jing-Lin Zhao, Yue-Jin Yang ⁎, Yuan-hui Zhang, Shi-Jie You, Yong-Jian Wu, Run-Lin Gao Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Li Shi Road 167, Xi-Cheng District, Beijing, 100037, China Received 31 December 2006; accepted 5 January 2007 Available online 25 April 2007
Abstract We investigated whether pretreatment with statin may prevent contrast-induced nephropathy in patients who underwent primary coronary intervention for acute myocardial infarction (AMI). A total of 279 consecutive patients who underwent successful primary angioplasty for a first AMI were studied. Contrast-induced nephropathy was defined as an increase in serum creatinine of ≥ 5 mg/dL after the primary PCI. 56 patients receiving statin treatment before admission had lower incidence of the contrast-induced nephropathy than those without it (7.1% and 20.6%, P b 0.01). Multivariable logistic regression analysis revealed that absence of statin pre-treatment was a significant predictor of the reperfusion arrhythmia along with anterior AMI, baseline creatinine value, time-to-reperfusion, higher volume of the contrast agent. Pretreatment with statin could reduce the contrast-induced nephropathy after primary coronary intervention in patients with AMI. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Myocardial infarction; Reperfusion; Statin
Contrast-induced nephropathy (CIN) is a complication of coronary diagnostic and interventional procedures. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to have beneficial effect on renal function [1]. However, little is known about the effect of pretreatment with statins on contrast-induced nephropathy in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). Therefore, in the present study, we investigated whether the statin treatment before the onset of acute myocardial infarction could reduce the CIN in patients who underwent primary coronary intervention. 1. Methods We studied 279 consecutive patients who underwent primary angioplasty for a first AMI between September 2001
and January 2005. Contrast-induced nephropathy was defined as an increase in serum creatinine of ≥ 0.5 mg/dL after the primary PCI. All patients received aspirin (300 mg) plus clopidigrel (300 mg) orally before coronary angiography. Coronary angiography was performed using the right femoral approach to determine culprit lesion and collateral channels. We performed coronary intervention with angioplasty and implanted a stent to reduce the residual diameter stenosis to b50%. Continuous variables were compared by one-way ANOVA. Comparisons of categorical variables were performed with the Fisher's exact test. Univariable and multivariable logistic regression analyses were used to identify independent predictors for the contrast-induced nephropathy. A value of P b 0.05 (2-sided) was considered statistically significant. 2. Results
☆
Supported, in part, by a grant-in-aid (30572439) from the National Natural Science Foundation of China. ⁎ Corresponding author. Tel.: +86 10 88398080. E-mail address: [email protected] (Y.-J. Yang). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.01.123
56 patients had chronically received statin before admission: 23 patients had received pravastatin (20–40 mg/day), 21 patients simvastatin (20–40 mg/day), and 12 patients
436
J.-L. Zhao et al. / International Journal of Cardiology 126 (2008) 435–436
Table 1 Clinical characteristics of patients with or without statin
Creatinine on admission (mg/dl) CIN, n (%) Total cholesterol (mg/dl) Triglycerides (mg/dl) Symptom onset-reflow time (h) EF on admission (%) SBP (mm Hg) Anterior wall infarction, n (%) Contrast volume (ml) Medication before AMI ACEI pre-treatment, n (%) β-Blocker pre-treatment, n (%) Aspirin pre-treatment, n (%)
With statin n = 56
Without statin n = 223
Pvalue
1.11 ± 0.3
1.09 ± 0.2
4 (7.1) 198 ± 43 107 ± 98 5.6 ± 4.3
46(20.6) 196 ± 52 101 ± 78 5.9 ± 5.2
47 ± 17 131 ± 31 38 (67.8)
48 ± 14 136 ± 26 148 (66.4)
0.36 0.41 0.79
336 ± 165
358 ± 223
0.26
12 (21.4)
48 (21.5)
0.91
6 (10.7)
19 (8.5)
0.12
18 (32.1)
78 (34.9)
0.89
0.18 − 0.05 0.47 0.56 0.41
⁎P values for the differences between the patients with or without statin. Data are presented as the mean value ± S.D. or number or percentage of patients. CIN, EF and SBP represent contrast-induced nephropathy, ejection fraction and systolic blood pressure respectively.
atrovastatin (10–20 mg/day). The 50 patients (17.9%) showed the contrast-induced nephropathy. These 50 patients were allocated to the contrast-induced nephropathy group, and the remaining 229 patients to the non-contrast-induced nephropathy group. The patients with the contrast-induced nephropathy had high incidence of anterior AMI, higher baseline creatinine value, longer time-to-reperfusion, lower left ventricular ejection fraction, and higher volume of the contrast agent during PCI than those without contrast-induced nephropathy. Number of the patients pretreated with statin was significantly lower in the contrast-induced nephropathy group than in the non-contrast-induced nephropathy group (8% vs 22.7%, P b 0.01). The incidence of contrast-induced nephropathy was significantly lower in patients with statin than in those without it (7.1% and 20.6%; P b 0.01). Statin pre-treatment was an independent predictor of the contrast-induced nephropathy along with anterior AMI, baseline creatinine value, time-toreperfusion, higher volume of the contrast agent (Table 1). 3. Discussion The present study demonstrated that the patients receiving statin pre-treatment had lower incidence of the contrast-
induced nephropathy than those without statin. Multivariable logistic analysis revealed that statin pre-treatment was an independent predictor for the contrast-induced nephropathy. The results indicated that statin could reduce contrastinduced nephropathy in patients undergoing primary PCI. To our knowledge, this is the first published report of statin pretreatment associated with reduction in contrast-induced nephropathy in patients with AMI. The exact mechanism of contrast-induced nephropathy is not known. Oxidation injury, vasoconstriction, injury from chemokines, tubular obstruction, mitochondrial injury, and plasma membrane toxicity have been implicated [2]. The patients with AMI treated with primary PCI represent a population at higher risk for contrast-induced nephropathy than those undergoing elective PCI. Several conditions may contribute to renal injury in this setting. Among them, hypotension or even shock, a large volume of contrast media, and the impossibility of starting a renal prophylactic therapy are the factors most likely involved. The precise mechanism, by which statin is beneficial in the reduction of the contrastinduced nephropathy, remains unclear. Its effects, including stabilization of vulnerable plaque, amelioration of endothelial dysfunction and inhibition of neutrophils [3], may provide some explanations. In addition, statin reduces ischemic and angiotensin-II-mediated acute renal failure [4]. These pleiotropic effects could contribute to the preventive effect of statin on contrast-induced nephropathy. In summary, pre-treatment with statin could reduce the contrast-induced nephropathy after primary coronary intervention in patients with AMI. References [1] Schouten O, Kok NF, Boersma E. Effects of statins on renal function after aortic cross clamping during major vascular surgery. Am J Cardiol 2006;97:1383–5. [2] Weisberg LS, Kurnik PB, Kurnik BR. Radiocontrast-induced nephropathy in humans role for vasoconstriction. Kidney Int 1992;41:1408–15. [3] Wan MX, Schramm R, Klintman D, et al. A statin-based inhibitor of lymphocyte function antigen-1 protects against ischemia/reperfusioninduced leukocyte adhesion in the colon. Br J Pharmacol 2003;140: 395–401. [4] Park JK, Muller DN, Mervaala EM, et al. Cerivastatin prevents angiotensin II-induced renal injury independent of blood pressure- and cholesterol-lowering effects. Kidney Int 2000;58:1420–30.