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Gestione dell’insufficienza renale nelle sindromi coronariche: prima e dopo lo studio emodinamico Rossana Fusco Dipartimento Cardio-Toraco-Vascolare A.De Gasperis Ospedale Niguarda Cà Granda -Milano 47° Convegno Cardiologia 2013 Milano 23-27 settembre
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An independent, graded association between lower levels of the estimated GFR and the risks of death, cardiovascular events, and hospitalization. These risks were evident with an estimated GFR of less than 60 ml per minute per 1.73 m2 and substantially increased with an estimated GFR of less than 45 ml per minute per 1.73 m2.
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2082 AMI patients and PCI The presence of CKD at baseline is associated with a striking increase in short-term and late mortality. For each decline in CrCl by 10 ml/min a significant incremental reduction in survival was evident
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Independent Predictors of 2y mortality at Cox regression analysis the CKMB and PCI study (n=2860) Variable Wald Chi square Hazard ratio 95% CI p-value Predictive information (%) Age*(continuous) 22.43 1.061.03-1.08<0.0001 25.6 Ejection fraction** (continuous) 22.18 0.960.94-0.98<0.0001 25.3 eGFR <45 ml 45-59.9 ml 60-74.9 ml >75 ml 18.102.840.961.0711.66-4.840.53-1.750.65-1.76 0.00010.890.79 20.7 Unsuccessful procedure 7.07 2.191.23-3.910.008 8.1 Atrial fibrillation 5.38 1.891.10-3.260.02 6.1 Diabetes mellitus 4.53 1.541.04-2.300.03 5.2 Fluoroscopy time*** 4.33 1.021.00-1.040.04 4.9 Acute Renal Failure 3.54 1.830.98-3.440.06 4.0 The CKMB and PCI study Roghi A, et al: JCM 2007
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Independent Predictors of Mortality in elderly Patients with ACS Morici N et al. Am J Cardiol 2013;112:1-7
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Risk Stratification in Patients with CKD and ACS Risk Stratification in Patients with CKD and ACS GRACE prediction score was used to calculate the 6-month mortality risk among 7638 patients and the baseline SCr at admission was the fifth strongest risk factor for death 1. 1. A validated prediction model for all forms of acute coronary syndrome: Estimating the risk of 6-month postdischarge death in an international registry JAMA 291: 2727–2733, 2004 Eagle KA et al.
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5 years mortality 4550 pts-Rate of PCI 75%
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Renal insufficiency reduce the likelihood of receiving treatment according to current guidelines and short term prognosis remains poor
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For the FIR collaboration RR 11,7%
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IS THERE ATTENUATION OF BENEFIT OF INVASIVE THERAPY IN PATIENTS WITH CHRONIC KIDNEY DISEASE? WITH CHRONIC KIDNEY DISEASE? The treatment disparity Comorbidities Higher procedural and vascular complications Increased bleeding Increased likelihood of restenosis Need of repeat revascularization Acute kidney injury NO RANDOMIZED CONTROLLED TRIALS
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Early invasive therapy is associated with greater 1-year survival in patients with non–ST- elevation myocardial infarction and mild-to-moderate renal insufficiency (HR 0.64,95% confidence interval 0.56 to 0.73, p<0.001) 1. Early invasive therapy is associated with greater 1-year survival in patients with non–ST- elevation myocardial infarction and mild-to-moderate renal insufficiency (HR 0.64,95% confidence interval 0.56 to 0.73, p<0.001) 1. The benefit declines with lower renal function and is less certain in those with renal failure or on dialysis. The benefit declines with lower renal function and is less certain in those with renal failure or on dialysis. 1. Szummer K et al. Circulation. 2009;120:851-858 23262 pts.PCI within 14 days
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7481 pts; 80% CKD stage 3; 20% CKD stage 3-5. Mortality rate in conservative arm were 2.5% to 10%
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ARF is a complex, multicausal dysfunction with clinical features ranging from small changes in SCr to anuric renal failure: the RIFLE classification is a proposed classification scheme for ARF, which includes separate criteria for creatinine and urine output (UO) 1. The classification system developed by the Acute Kidney Injury Network (AKIN) applies the concept of small changes in SCr over a short period of time with the main purpose of allowing for early diagnosis and treatment of AKI. 1.Definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8: R204–R212 Bellomo R et al. 2.Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 11: R31, 2007 Mehta RL et al. Acute Renal Failure and Acute Kidney Injury: Definition Acute Renal Failure and Acute Kidney Injury: Definition
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Acute Renal Failure and Acute Kidney Injury Risk Factors for Mortality in ACS? Acute Renal Failure and Acute Kidney Injury Risk Factors for Mortality in ACS? Little information about the role of ARF in clinical outcomes after ACS (lack of standardization of the diagnosis of ARF/ > 30 definitions in the medical literature); RIFLE and AKIN definitions establish the new concept of acute kidney injury (AKI) => important difference is that injury precedes failure. Small increases in SCr during hospitalization are actually associated with a worse prognosis for the patient (table 3). a The criteria used to diagnose AKI were not AKIN or RIFLE.
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Retrospective study 3,210 patients with ACS. AKI was identified on the basis of the changes according to the AKI Network Criteria.
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Retrospective study 14782 adults who receive coronary angiography. 70% ACS AKI is defined according to Acute Kidney Injury Network Criteria
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Prevention of Contrast-induced acute kidney injury Identify High-risk patients Hold Furosemide (?), ACE inhibitor (?), Metformin (?) Hydration Hydration : Half-normal saline (0.45%) or normal saline (0.9%) Sodium bicarbonate? LOCM or IOCM Limited amount of Contrast Media <140 ml (Briguori et al.) <5 ml x weight/sCr (McCullough et al.) Acetylcysteine
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Risk of AKI Mehran et al. JACC 2004;44:1393–9)
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Early infusion Early infusion : bolus of 3ml/kg/h of sodium bicarbonate in 1 hour -> 1 ml/kg/ h for 12 hours Late infusion : Late infusion : isotonic saline (NaCl 0.9%) at a rate of 1 mL / kg /h for 12 hours. The infusion rate was reduced to 0.5 mL / kg /h when concomitant left ventricular dysfunction. No idratation
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Mechanisms of Bicarbonate Alkalinization of renal tubular fluid may reduce injury by free-radicals formation promoted by an acidic environment Buffering the higher amount of H + due to cellular hypoxia Facilitate Na+ reabsorption through the electrogenic Na+/HCO 3 - co-trasporter Dose protocol: 154 mEq/L at 3 ml/kg/h for 1 hour before contrast and then 1 ml/kg/h for 6 hours after contrast
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Meier P et al. BMC Medicine 2009; 7: 23
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174 consecutive patients (mean age 73+ 7 year; mean GFR 39 + 10 ml/min/1.73 m2)
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rugRecommendations in case of CKD Oral P2Y12 antagonist No information in patients with renal failure Enoxaparin*Dose reduction to 1 mg/kg once daily in severe renal failure (GFR 75 years old), it is recommended to calculate GFR and to monitor anti Xa activity. FondaparinuxContraindicated in severe renal failure (GFR <20ml/min). However, as much lower risk of bleeding complications were observed in Oasis-5 with fondaparinux as compared with enoxaparin, even in patients with severe renal failure, this drug might be the anticoagulant of choice in this situation (GFR 30-59 ml/min) BivalirudinContraindicated in severe renal failure (GFR <30ml/min) and in dialysis-dependent patients. In patients with moderate renal failure (GFR 30-59 ml/min) a lower initial rate 1.4 mg/kg/h should be given. No reduction in the bolus dose is needed. TirofibanDose adaptation required in patients with renal failure. 50% of the dose only if GFR <30ml/min. EptifibatideAs 50% of eptifibatide is cleared through the kidney in patients with renal failure, precautions must be taken in patients with impaired renal function (GFR > 30 to <50ml/min). The infusion dose should be reduced to 1µg/kg/min in such patients. The dose of the bolus remains unchanged at 180µg/kg. Eptifibatide is contraindicated in patients with creatinine clearance <30mL/min. AbciximabNo specific recommendations for the use of abciximab, or for dose adjustment in case of renal failure. Careful evaluation of haemorrhagic risk is needed before using the drug in case of renal failure. ESC 2011 NSTEACS guidelines Chronic kidney disease
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Capodanno et.Circulation 2012: 125: 2649 Oral P2Y12 antagonist in Renal Dysfunction
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░Wider use of coronary angiogram/intervention in CKD patients with ACS ░In the setting of evolving STEMI, ST segment depression / raised cardiac marker ACS with sign of acute HF/cardiogenic shock, there is no degree of renal dysfunction that constitutes a controindication to immediate coronary intervention. In these situations, patient’s life is at risk and an aggressive approach is required to reperfuse the ischemic myocardium. This practice will also give us the opportunity to study the effectof myocardial revascularization in patients with advanced CKD-a subgroup that has usually been excuded ░Prophylactic intervention should be instituted to reduce the risk of ICI- AKI prior to coronary angiography These include intravascular volume expansion with isotonic saline or sodium bicarbonate, employing iso- osmolaror a nonionic low osmolality contrast medim and limiting the dose of contrast medium to the minimum volume compatible with the diagnostic study ░Integration of an interventional approach into routine management of CKD stage IV and V patients may increase the risk of progression of renal disease and need for renal replacement therapy in a subset of these patients- a “renal “ price to pay for better cardiac outcomes, but worth the value Management of Acute Coronary Syndrome in patients with CKD: If we don’t risk anything, we risk even more If we don’t risk anything, we risk even more Asim M Nephrology Section, Hamad General Hospital
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4634 pts followed for 1 years4634 pts followed for 1 years Primary outcome: reduced renal function (50% decrement of GFR or development of ESRD) or occurence of deathPrimary outcome: reduced renal function (50% decrement of GFR or development of ESRD) or occurence of death Exclusion criteria GFR <30 ml/minExclusion criteria GFR <30 ml/min
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100% 80% 60% 40% 20% 0% CKD category Stage 3a = 59.0 Stage 3a = 46.2 Stage 3b = 27.1 Stage 3b = 31.2 Stage 4 = 9.5 Stage 4 = 14.1 Stage 5 = 4.4 Stage 5 = 8.5 STEMI No CKD= 69.5% (N 13,221) CKD= 30.5% (5,808) NSTEMI No CKD= 57.1% (N 17,393) CKD= 42.9% (N 13,069) 100% 80% 60% 40% 20% 0%
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p = 0.038 Standard Dose (600 mg BID) Double Dose (1200 mg BID) Cases without event Cases with event 11% 89% 3.5% 95.5% Briguori C. et al. Eur Heart J 2004; 25: 206-11 Standard Dose (600 mg BID) Acetylcysteine and CI-AKI The N-acetylcysteine effect is dose-dependent Standard dose = 600 mg iv before procedure & 600 mg orally twice daily for 48 hours. Total dose = 3 g Standard dose = 600 mg iv before procedure & 600 mg orally twice daily for 48 hours. Total dose = 3 g High dose = 1200 mg iv before procedure & 1200 mg orally twice daily for 48 hours. Total dose = 6 g
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Renal dysfunction is present in approximately 30–40% of patients with ACS and is associated with a worse prognosis and increased bleeding risk. Decisions on reperfusion in patients with STEMI have to be made before any assessment of renal function is available, but it is important to estimate the glomerular filtration rate as soon as possible after admission. ACS patients with chronic kidney disease are frequently overdosed with antithrombotics, leading to increased bleeding risk.
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