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Hội nghị tim mạch tồn quốc Ninh Bình, 6-8/11/2015 How to reduce contrast-induced acute kidney injury in ACS patients? Dinh Duc Huy, MD, FSCAI Tam Duc Heart Hospital 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 Strategy for Management of Patients With Risk Factors for Contrast-Induced Nephropathy JAMA 2006;295:2765-2779 Early high-dose Rosuvastatin for Contrast-Induced Nephropathy Prevention in ACS (The PRATO-ACS) Exclusion criteria: • Emergency (within hours) angiography • Acute renal failure or ESRF requiring dialysis • Baseline serum creatinine ≥ 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 Methods Study Design Statin-naive & Early Invasive Strategy NSTE-ACS patients R CCU-Admission Rosuvastatin ~ 24 H Controls 40 mg (LD) then 20 mg/day Hydration, N-Acetylcystein Contrast Coronary Angiography ± PCI 72 H Primary Endpoint: CI-AKI ↑ Cr ≥ 0.5 mg/dl or ≥ 25 % within 72 hrs of contrast exposure J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 Additional Protocol Details Antiplatelet treatment: ASA (300 mg LD, 100 mg/day MD) Clopidogrel (600 mg LD, 150 mg/day→ discharge) • • • Hydration i.v.12 hrs pre and post contrast medium (isotonic saline 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) At discharge: Clopidogrel 75 mg/day, ASA 100 mg/day & Rosuvastatin group Rosuvastatin Discharge 20 mg/day (10 mg/day if CrCL< 30 ml/min) Controls Atorvastatin 40 mg/day J Am Coll Cardiol 2014;Jan 7-14;63(1):71-9 Baseline Clinical and Demographic Rosuvastatin Control p value 66.2 ± 12.4 66.1 ± 13.5 0.91 46.4 44.8 0.72 34 34 0.93 26.2 ± 3.7 26.6 ± 4.4 0.35 NSTE-MI 92.4 92.1 >0.90 Unstable angina 7.5 7.9 >0.90 Hypertension 56.7 54.8 0.65 Diabetes mellitus 19.8 22.6 0.45 Creatinine clearance < 60ml/min 41.7 41.7 >0.90 Previous MI 9.5 5.9 0.13 Previous PCI or CABG 11.9 7.1 0.07 50 ± 50 ± >0.90 EF < 45% 33.3 33.7 0.93 High Clinical Risk Level, % 71.4 67.1 0.29 Age Age ≥ 70 years.% Female, % Body Mass Index Clinical presentation, % Risk factors, % Baseline LV EF (%) 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 was significantly higher in patients ≥75 years (15.9% vs 8.7%, OR 2.001; 95% CI 1.14-3.53, P= 0.015) No significant interaction was observed between age and statin treatment (P= 17) 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 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 DM and concomitant CKD had arterial angiography with or without percutaneous intervention • Receive rosuvastatin 10 mg/day (n=1,498) for days (2 days before, & 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 Primary endpoint- the development of CI-AKI Increase in serum creatinine concentration ≥0.5 mg/dl 0.25% above baseline at 72 h after exposure to contrast medium J Am Coll Cardiol 2014;63:62–70 Main findings Lower CI-AKI in rosuvastatin group (2.3% vs 3.9%, p= 0.01); NNT= 65 In patients with stage CKD, CI AKI was 1.5% vs 3.3% (p= 0.01) No significant differences in all-cause deaths (p= 0.73) or dialysis/hemofiltration p= 0.50) Less of worsening HF following rosuvastatin treatment (p= 0.02) J Am Coll Cardiol 2014;63:62–70 Multivariable Analysis- Predictors of CI-AKI Independent predictors • baseline ACS • NYHA functional class • decreased e-GFR 2.The benefit of rosuvastatin was consistent among various subgroups Rosuvastatin and hemoglobin were independently associated with a decreased risk of CI-AKI J Am Coll Cardiol 2014;63:62–70 Am J Cardiol 2014;114:541-548 Inclusion criteria RCTs of patients who were statin-naïve or not who did not consume statins in the 30 days before CAG or PCI 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) CI-AKI reported and defined as serum creatinine increase from baseline ≥25% or ≥0.5 mg/dl within the first 48 to 72 hours 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 The incidence of CI-AKI: 3.0%- 16.1% across studies 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) 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 vs GFR > 60 ml/min Am J Cardiol 2014;114:541-548 Statin type and N-acetyl cysteine or hydration did not significantly influence the results Non-rosuvastatin vs rosuvastatin NAC vs hydration Am J Cardiol 2014;114:541-548 Subgroup of diabetes patients in other meta-analysis 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) 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 Which statin for preventing CIN? • 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 BioMed Research International Volume 2014, http://dx.doi.org/10.1155/2014/213239 Conclusions Pre-procedural (angiography with or without intervention) statin use leads to a significant reduction in the risk reduction of CIAKI Old patients & patients with chronic kidney disease, or diabetes are the categories who would benefit the most 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!