How to reduce contrast-induced acute kidney injury in ACS patients?

 kidney injury in ACS patients? 
Dinh Duc Huy, MD, FSCAI 
Tam Duc Heart Hospital 
Hội nghị tim mạch toàn quốc 
Ninh Bình, 6-8/11/2015 
Contrast induced AKI 
 Major complication with adverse outcomes after contrast 
medium injection. 
 Low incidence in patients with normal renal function. 
 Dramatically higher in patients with DM, CKD. 
 Mechanisms are complex. 
 May be related to direct renal tubular toxicity, 
vasoconstriction, and high oxidative stress. 
A Simple Risk Score for Prediction of 
Contrast induced Nephropathy After PCI 
J Am Coll Cardiol 2004;44:1393–9 
How to prevent CI-AKI? 
 The best approach remains unclear. 
 Current recommendations only include adequate 
preparatory hydration (Normal Saline 1mg/kg per hour 
12-24 hours pre-procedure). 
 Lack of conclusive evidence in other strategies such as 
administration of NAC as an antioxidant, sodium 
bicarbonate-based hydration and consideration of the 
type of contrast used. 
Strategy for Management of Patients With 
Risk Factors for Contrast-Induced Nephropathy 
JAMA. 2006;295:2765-2779 
JAMA. 2006;295:2765-2779 
Strategy for Management of Patients With Risk 
Factors for Contrast-Induced Nephropathy 
Early high-dose Rosuvastatin for 
Contrast-Induced Nephropathy Prevention in ACS (The 
PRATO-ACS) 
Exclusion criteria: 
• Emergency (within 2 hours) angiography 
• Acute renal failure or ESRF requiring dialysis 
• Baseline serum creatinine ≥ 3 mg/dl 
• Contraindications to statin treatment 
• Contrast administration within the last 10 days 
• Refusal to consent 
Primary Endpoint: 
↑ Cr ≥ 0.5 mg/dl or ≥ 25 % within 72 hours of contrast exposure 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Statin-naive & Early Invasive Strategy NSTE-ACS patients 
Coronary Angiography ± PCI 
Hydration, N-Acetylcystein 
Methods 
Study Design 
CCU-Admission 
Contrast 
CI-AKI 
Controls Rosuvastatin 
40 mg (LD) then 20 mg/day 
R 
Primary Endpoint: 
↑ Cr ≥ 0.5 mg/dl or ≥ 25 % within 72 hrs of contrast exposure 
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J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
• Hydration i.v.12 hrs pre and post contrast medium 
 (isotonic saline 1 ml/kg/h or 0.5 ml/kg/h if LV-EF < 40% ) 
• Oral NAC 24 hrs pre and post contrast medium (2400 mg/day) 
• Nonionic, dimeric iso-osmolar contrast medium (Iodixanol) & 
Power injector (ACIST) 
Additional Protocol Details 
At discharge: Clopidogrel 75 mg/day, ASA 100 mg/day & 
Antiplatelet treatment: 
 ASA (300 mg LD, 100 mg/day MD) 
 Clopidogrel (600 mg LD, 150 mg/day→ discharge) 
Rosuvastatin 
20 mg/day 
(10 mg/day if CrCL< 30 ml/min) 
Discharge 
Atorvastatin 
40 mg/day 
Rosuvastatin group Controls 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Baseline Clinical and Demographic 
Rosuvastatin Control p value 
Age 66.2 ± 12.4 66.1 ± 13.5 0.91 
Age ≥ 70 years.% 46.4 44.8 0.72 
Female, % 34 34 0.93 
Body Mass Index 26.2 ± 3.7 26.6 ± 4.4 0.35 
Clinical presentation, % 
 NSTE-MI 92.4 92.1 >0.90 
 Unstable angina 7.5 7.9 >0.90 
Risk factors, % 
 Hypertension 56.7 54.8 0.65 
 Diabetes mellitus 19.8 22.6 0.45 
 Creatinine clearance 0.90 
 Previous MI 9.5 5.9 0.13 
 Previous PCI or CABG 11.9 7.1 0.07 
Baseline LV EF (%) 50 ± 9 50 ± 9 >0.90 
EF < 45% 33.3 33.7 0.93 
High Clinical Risk Level, % 71.4 67.1 0.29 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Procedural data 
Rosuvastatin Control p value 
Randomization-to-Contrast time (hrs) 22.5 (14 – 43) 23 (15 – 45.5) 0.79 
Multivessel disease, % 48.8 47.6 0.78 
Contrast volume (ml) 149.7 ± 86.8 138.2 ± 77.8 0.14 
Contrast volume >140 ml 46.4 40.1 0.15 
Therapeutic strategy, % 0.70 
 Medical treatment 21.4 23.8 
 CABG 10.7 11.9 
 PCI 67.9 64.3 
PCI data 
 Multivessel PCI 33.9 28.3 0.21 
 Contrast volume (ml) 183 ± 80 172 ± 72 0.18 
 Contrast volume >140 ml, % 64.9 59.8 0.20 
CI-AKI Mehran risk score, median (IQR) 3 (1 – 6) 2 (1 – 5) 0.36 
 ≤ 5, % 74.2 76.6 
 >5, % 25.8 23.4 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
CI-AKI Primary Endpoint 
( 0.5 or  25% within 72 hrs) 
NNT = 12 
ORcrude (95% CI): 
 0.41 (0.22 - 0.74) 
ORadjusted (95% CI): 
 0.38 (0.20 – 0.71) 
*Adjusted for: Sex, Age, Diabetes, Hypertension, LDL-cholesterol, 
Creatinine Clearance, LV-EF, Contrast Volume, CI-AKI Risk Score 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Additional Endpoints 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Defined by other criteria 
Pre-specified Subgroups 
Additional Endpoints: 
Adverse Clinical Events (30 days) 
J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 
Post Hoc Analysis of the PRATO-ACS Trial 
CI-AKI in the Elderly 
CI-AKI rate (A) and mean creatinine increase (B) 
 by age (75 years) and statin treatment. 
Journal of Cardiovascular Pharmacology and Therapeutics, DOI: 10.1177/1074248415599062 
Post Hoc Analysis of the PRATO-ACS Trial 
CI-AKI in the Elderly 
1. CI-AKI was significantly higher in patients ≥75 years (15.9% 
vs 8.7%, OR 2.001; 95% CI 1.14-3.53, P= 0.015) 
2. No significant interaction was observed between age and 
statin treatment (P= 0 .17). 
3. Pre-treatment with rosuvastatin was associated with 65% RR 
in CI-AKI rate (12.9%vs 4.5%) in younger patients and 38% 
(19.5% vs 12%) in elderly individuals. 
4. The greatest protective effect of statin treatment was seen in 
patients with the highest hs-CRP values in both age-groups 
Journal of Cardiovascular Pharmacology and Therapeutics, DOI: 10.1177/1074248415599062 
Methods 
• 2,998 patients with type 2 DM and concomitant CKD had arterial 
angiography with or without percutaneous intervention. 
• Receive rosuvastatin 10 mg/day (n=1,498) for 5 days (2 days 
before, & 3 days after procedure) or standard-of-care (n=1,500). 
• Renal function was assessed at baseline, 48 h, and 72 h after 
exposure to contrast medium. 
J Am Coll Cardiol 2014;63:62–70 
Increase in serum creatinine concentration ≥0.5 mg/dl 0.25% above 
baseline at 72 h after exposure to contrast medium. 
Primary endpoint- the development of CI-AKI 
J Am Coll Cardiol 2014;63:62–70 
J Am Coll Cardiol 2014;63:62–70 
Main findings 
1. Lower CI-AKI in 
rosuvastatin group (2.3% 
vs. 3.9%, p= 0.01); NNT= 
65 
2. In patients with stage 2 
CKD, CI AKI was 1.5% vs. 
3.3% (p= 0.01) 
3. No significant differences 
in all-cause deaths (p= 
0.73) or 
dialysis/hemofiltration p= 
0.50) 
4. Less of worsening HF 
following rosuvastatin 
treatment (p= 0.02) 
Multivariable Analysis- Predictors of CI-AKI 
J Am Coll Cardiol 2014;63:62–70 
Rosuvastatin and hemoglobin were 
independently associated with a 
decreased risk of CI-AKI 
1. Independent 
predictors 
• baseline ACS 
• NYHA functional 
class 
• decreased e-GFR 
2.The benefit of 
rosuvastatin was 
consistent among 
various subgroups 
Am J Cardiol 2014;114:541-548 
Inclusion criteria 
1. RCTs of patients who were statin-naïve or not who did not 
consume statins in the 30 days before CAG or PCI 
2. Control group consisting of patients who did not consume 
statins and received placebo or standard therapy, defined as 
saline solution or NAC and/or sodium bicarbonate (other drugs 
were excluded) 
3. CI-AKI reported and defined as serum creatinine increase from 
baseline ≥25% or ≥0.5 mg/dl within the first 48 to 72 hours 
4. Studies investigating statin use in patients undergoing coronary 
angiography or PCI 
Am J Cardiol 2014;114:541-548 
Lower CI-AKI in statin group 
Am J Cardiol 2014;114:541-548 
Main findings from meta-analysis 
1. The incidence of CI-AKI: 3.0%- 16.1% across studies 
2. Overall, the incidence of CI AKI was 3.91% in the statin group 
(n= 2,480) and 6.98% in the control group (n= 2,504) 
3. Using random effects model, patients receiving statins had 
46% lower RR of CI-AKI compared with the control group (RR 
0.54,95% CI 0.38 to 0.78, p= 0.001) 
Am J Cardiol 2014;114:541-548 
GFR 60 ml/min. 
Am J Cardiol 2014;114:541-548 
Non-rosuvastatin vs rosuvastatin 
Am J Cardiol 2014;114:541-548 
NAC vs hydration 
Statin type and N-acetyl cysteine or hydration 
did not significantly influence the results 
The RR in diabetic patients was 39% (p=0.005), and in patients without diabetes was 
39% (p=0.11). The difference in risk reduction of CIN was not statistically significant 
between both groups (p=0.99). 
Subgroup of diabetes patients 
in other meta-analysis 
Benefit of statin pretreatment in prevention of contrast-induced nephropathy in different adult patient population: systematic review 
and meta-analysis. Singh N, Lee JZ, Huang JJ, et al. Open Heart 2014 
 14 trials with 6,160 patients were included, focusing on 
atorvastatin, rosuvastatin, simvastatin and placebo or no statin 
therapy. 
 The risk of CI nephropathy was reduced by atorvastatin high 
dose and rosuvastatin high dose. 
 High dose atorvastatin and rosuvastatin before iodinated 
contrast administration have a consistent and beneficial 
preventive effect and may actually halve its incidence. 
• Atorvastatin high dose (OR versus 
placebo = 0.49; 95% CI 0.32–0.74) 
• Rosuvastatin high dose (OR= 0.49). 
• Very similar effect (OR = 1.00) 
between atorvastatin high dose and 
rosuvastatin high dose. 
• Simvastatin high dose was 
inconclusive. 
• Atorvastatin low dose and 
simvastatin low dose were not in 
favor to prevent CIN 
Which statin for 
preventing CIN? 
BioMed Research International Volume 2014,  
Conclusions 
1. Pre-procedural (angiography with or without intervention) statin 
use leads to a significant reduction in the risk reduction of CI-
AKI. 
2. Old patients & patients with chronic kidney disease, or diabetes 
are the categories who would benefit the most. 
3. In the setting of ACS, high-dose rosuvastatin given on admission 
to statin-naïve patients who are scheduled for an early invasive 
strategy can prevent CI-AKI and improve short-term clinical 
outcome. 
Thank you for your attention!