How to manage ACS patients with Comorbidities? Patients with Renal Failure

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1 How to manage ACS patients with Comorbidities? Patients with Renal Failure François Schiele, MD, PhD Department of Cardiology, University Hospital Jean Minjoz, Besançon, France. Potential conflicts of interest Research grant : GlaxoSmithKline, Sanofi-Aventis, Servier, Daiichi-Sankyo/Lilly Speaker : Boehringer Ingelheim, Daiichi-Sankyo/Lilly, Novartis, Sanofi-Aventis, Servier, Astra Zeneca, GlaxoSmithKline. Consulting : Sanofi, Astra Zeneca, Daiichi-Sankyo/Lilly

2 How to manage ACS pts with Renal Failure? Main specific points for patients with renal failure: 1. Detection of CKD as soon as possible. 2. Diagnosis of ACS and Risk stratification. 3. Anticoagulants and Antiplatelets. 4. Reperfusion, Early invasive strategy and Acute Kidney Injury. 5. Treatment and outcomes.

3 Detection of CKD as soon as possible 1. ESC Guidelines for STEMI and NSTE-ACS recommend to assess egrf to detect Chronic Kidney Disease: Creatinine Clearance (Cockroft-Gault) or egfr (MDRD equation). 2. MDRD is preferred, 5 stages of CKD. Hamm ESC guidelines 2011 Eur H J 2011 Levey A. Ann Intern Med 2003;139:

4 Detection of CKD as soon as possible 4. Decreased acuracy of the MDRD and poor prognostic value in patients with high egfr. Use CKD-EPI formula, no specific biological assessment. Estimated/CKD-EPI vs measured Levey Am J Intern Med 2009;150:604-12

5 Detection of CKD as soon as possible 1. ESC Guidelines for STEMI and NSTE-ACS recommend to assess egrf to detect Chronic Kidney Disease: Creatinine Clearance (Cockroft-Gault) or egfr (MDRD equation). 2. MDRD is preferred, 5 stages of CKD. 3. Cystatin C : better relation with all cause mortality, but expensive Shlipak. NEJM 2005;352:2049

6 Diagnosis of ACS in CKD patients 1. Among patients with acute chest pain, CKD indicates higher likelihood for ACS. Khambatta Translational Research 2012;159:391-6

7 Diagnosis of ACS in CKD patients 1. Among patients with acute chest pain, CKD indicates higher likelihood for ACS. 2. Troponin T is elevated in end stage renal disease without ACS and decreased GFR increases the odds of having Troponin* 3. Same issue with hs_tn assay: more sensitive and specific, but more often positive in non cardiac cause, including Acute and Chronic RF.** 4. In patients with CKD, suspected for ACS, Troponin can only be used to rule out the diagnosis of NSTEMI*** 5. BNP and T-BNP levels are less reliable in patients with CKD: high level without HF**** *Frankel W. Am J Clin Pathol 1996;106: *Jeremias A. Ann Intern Med 2005;142: ***Aviles R. N Engl J Med 2002;346: **** Tsutamoto T. J Am Coll Cardiol 2006;47:582 ** Reichlin NEJM 2009;361:858-67

8 Risk stratification in CKD patients 1. Patients with CKD often have more comorbidities and high risk features*. The GRACE risk score contains the information about the renal function. Independent predictor of in-hospital and 6 month mortality (adjusted for baseline conditions)**. 2. As compared with egfr>60ml/min, egfr increase the risk of death by 3.5 and egfr<30 ml/min, by 6.3. CKD increases mortality, even after adjustment for treatments***. *Wright S. Ann Intern Med 2002;137:563 **Granger Arch Intern Med 2003;163: ***Schiele Am Heart J 2006;151:661

9 Risk stratification in CKD patients 1. Patients with CKD often have more comorbidities and high risk features*. The GRACE risk score contains the information about the renal function. Independent predictor of in-hospital and 6 month mortality (adjusted for baseline conditions)**. 2. As compared with egfr>60ml/min, egfr increase the risk of death by 3.5 and egfr<30 ml/min, by 6.3. CKD increases mortality, even after adjustment for treatments***. 3. Albuminuria is related to higher CV risk in ACS patients, on top of GRACE score****. *Wright S. Ann Intern Med 2002;137:563 **Granger Arch Intern Med 2003;163: ***Schiele Am Heart J 2006;151:661 ****Schiele Am Heart J 2009;157:327

10 Risk stratification in CKD patients 4. CKD patients treated with antithrombotics more often have bleeding complications. In non ACS patients treated for AF (HAS-BLED Score).

11 Risk stratification in CKD patients 4. CKD patients treated with antithrombotics more often have bleeding complications. In non ACS patients treated for AF (HAS-BLED Score). In ACS patients, CRUSADE Bleeding score

12 Risk stratification in CKD patients 4. CKD patients treated with antithrombotics more often have bleeding complications. In non ACS patients treated for AF (HAS-BLED Score). In ACS patients, CRUSADE Bleeding score In ACS patients treated with PCI ( PCI from NCVDR) Mehta Circ Cardiovasc Interv 2009;2:222-9

13 Anticoagulants and Antiplatelets Only UFH has label for patients with severe KD (CrCl<30mL/min). «New» AC (Enoxaparin, fondaparinux, bivalirudine) can be used as «one shot» (during PCI). Prolonged use lead to accumulation and bleeding complications 30-day outcomes NACE MACE Death MI Ischemic TVR Major bleeding CrCl < 60 ml/min CrCl 60 ml/min Bival better UFH + GPI better Bival better UFH + GPI better Saltzman JACC Intv 2011;4:

14 Anticoagulants and Antiplatelets Only UFH has label for patients with severe KD. «New» AC (Enoxaparin, fondaparinux, bivalirudine) can be used as «one shot» (during PCI). Prolonged use lead to accumulation and bleeding complications Enoxaparin in Pts with Renal Impairment Undergoing PCI ; The STEEPLE Trial Non-CABG-related major bleeding Non-CABG-related major & minor bleeding White Am Heart J 2009;157:

15 Anticoagulants and Antiplatelets Only UFH has label for patients with severe KD (CrCl<30mL/min). «New» AC (Enoxaparin, fondaparinux, bivalirudine) can be used as «one shot» (during PCI). Prolonged use lead to accumulation and bleeding complications. Fondaparinux with Renal Impairment Sub study from OASIS V Fox Ann Intern Med 2007;147:304.

16 Major bleeding events (%) Anticoagulants and Antiplatelets GP IIb/IIIa Inhibitors and Renal Dysfunction? The use of GP IIb/IIIa inhibitors decreases as renal function declines GP IIb/IIIa inhibitors in pts with ACS and renal insufficiency resulted in : Decreased risk of in-hospital mortality : OR = 0.34 [ ]; p=0.04 Increased bleeding events : OR = 2.13 [ ]; p< Freeman JACC 2003;41:

17 Anticoagulants and Antiplatelets Capodanno Circulation 2012;125:

18 Reperfusion, Early invasive strategy and Angioplasty Invasive strategy in CDK patients Patients with CrCl<60 ml/min benefit from invasive management and revascularization. Those treated only medically have the worst survival at 3 months. Large Swedish registry ( patients) indicates that patients with CrCl do not benefit from invasive approach and even adverse effect on patients with end-stage renal failure Keeley Am J Cardiol 2003;92:509 Szummer Circulation 2009;120:851-8.

19 Reperfusion, Early invasive strategy and Angioplasty ACTION Registry (40074 NSTEMI pts), patients with CKD: CKD patients managed invasively have more advanced coronary disease than those with normal renal function. They have higher mortality and more major bleedings. Hanna JACC Interv 2011;4:

20 Reperfusion, Early invasive strategy and Angioplasty Reperfusion in CDK patients with STEMI STEMI Patients with CKD benefit from reperfusion as much as patients with normal renal function. Advantage of PPCI over fibrinolysis is greater in CKD patients. In the GRACE registry, in STEMI patients with CKD, no mortality benefit with fibrinolysis, but with primary PCI in moderate CKD, not severe CKD Chang, Ann Acad Med Singapore 2010;39:179. Medi, JACC Interv 2009;2:26.

21 Reperfusion, Early invasive strategy and Angioplasty Acute Renal Failure Acute Kidney Injury: Complex and multicausal dysfunction, often neglected. Defined by elevation of creatinine or decrease in urine output (simply by worsening of renal function). Two definitions. Levey Am J Kidney 2007;40:153 Bellomo Crit Care 2006;10:R204

22 Reperfusion, Early invasive strategy and Angioplasty Acute Renal Failure Acute Kidney Injury: Complex and multicausal dysfunction, often neglected. Defined by elevation of creatinin or decrease in urine output (simply by worsening of renal function). Two definitions. Role of contrast induced nephrotoxiticy; difficult to prevent, but possible to predict, according to baseline characteristics and amount of contrast medium used. Mehran JACC 2004;44:1393

23 Reperfusion, Early invasive strategy and Angioplasty Acute Renal Failure Acute Kidney Injury: Complex and multicausal dysfunction, often neglected. Defined by elevation of creatinin or decrease in urine output (simply by worsening of renal function). Two definitions. Role of contrast induced nephrotoxiticy; difficult to prevent, but possible to predict, according to baseline characteristics and amount of contrast medium used. AKI and ARF are independent predictors of mortality in ACS. Parikh Arch Intern Med 2008;168:987

24 ACS and CKD 1. CKD is frequent in patients with ACS; many prognostic and therapeutic implications => early detection by egfr estimation. 2. All stages of CKD carry higher ischemic and bleeding risks. 3. In CKD patients, medication should be used as for non CKD patients, but with dose reduction, mainly for anticoagulants. New and more potent antiplatelet agents are beneficial, despite the higher bleeding risk. 4. Invasive strategies are beneficial, except in end stage CKD. Particular caution with the risk of AKI, often under estimated. 5. Higher mortality after ACS in CKD patients in not clearly related to sub optimal treatment. Need for specific therapies targeting specific pathophysiology associated with CKD.