Xử trí hội chứng vành cấp ở người có bệnh thận mạn

Background • The incidence of AMI is increased in this vulnerable subgroup • Atypical clinical presentation of AMI may be more frequent • ECG changes that may mimic or obscure AMI • L

Management of Acute Coronary Syndrome in

Chronic Kidney Disease

Dafsah Arifa Juzar Indonesian Heart Association Harapan Kita, Jakarta, Indonesian

Background

• The incidence of AMI is increased in this vulnerable subgroup

• Atypical clinical presentation of AMI may be more frequent

• ECG changes that may mimic or obscure AMI

• Left ventricular hypertrophy is common

• patients with renal dysfunction are more prone to adverse events

• Cardiovasscular medication : antiplatelets & anticoagulation,

• Cardiovascular procedures : coronary

• Relative lack of evidence and potential for uncertainty in selecting

medications

Clinical Presentation of ACS Among

CKD Patients

Szummer K et al J Intern Med 2010;268:40–49

Unique pathobiology of CKD

• greater luminal encroachment and

• higher plaque burden

• greater necrotic core and dense calcium with less fibrous tissue

• modulate coronary atherosclerotic plaque

composition to a less stable phenotype

– Metalloproteinases are elevated

– potentiates foam cell generation by enhancing

macrophage entry

• accelerated infarct expansion in association with enhanced inflammation and oxidative stress,

Baber U, etal JACC Cardiovasc Imaging 2012;5:S53–S61

Ponda MP etal Atherosclerosis 2010;210:57–62

Naito K, Anzai, etal J Card Fail 2008;

Pelisek J, etal P J Vasc Surg 2011

Prone to adverse event

Gibson CM, etal Eur Heart J 2004;25:1998–2005

Age adjusted Hazard Ratio for death from any

cause CV event & Hospitalization

1,200,295 ambulatory adults

Go AS et al N Engl J Med 2004;351:1296–1305

Conservative (C) VS Invasive (I)

protocol defined bleeding TACTIC TIMI IB

Januzzi J, etal Am J Cardiol 2002 Dec 1;90(11):1246-9

Relevance CKD in ACS

• underutilization of known cardio-protective therapies,

• less aggressive treatment,

• more frequent errors in dosing with excess toxicity from conventional therapies

Diagnostic

Cardiac biomarker

Cardiac Biomarker in CKD

EGFR < 60 98,8%

EGFR > 60 99,2%

Mueller C, etal Ann Emerg Med 2016;68:76-87

Gibson CM, etal Eur Heart J 2004;25:1998–2005

Reperfusion Strategy

Crude rates and adjusted odds ratios for death

by CKD stages stages

Caroline S Fox et al Circulation 2010;121:357-365

Early PCI in AMI

Huang HD et al International journal of cardiology 2013;168:3741-6

Incidence of adverse outcome & 6 mo

death stratified by renal function

GFR > 60 ml/mnt/1.73m2 GFR 30-59 ml/mnt/1.73m2 GFR < 30 ml/mnt/1.73m2

Medi C, J Am Coll Cardiol Intv 2009;2(1):26-33

STEMI reperfusion vs non reperfusion

by renal function

Medi C, J Am Coll Cardiol Intv 2009;2(1):26-33

GRACE registry data

Incidence of Stroke and major bleeding

Medi C, J Am Coll Cardiol Intv 2009;2(1):26-33

PCI

Early revascularization

• associated with reduced

mortality in ACS patients

with CKD, including those

with severe CKD or

receiving dialysis

PCI – Risk of contrast

Huang HD et al 2013;168:3741-6

*Plans should be made in case CI-AKI occurs and dialysis is required

**IV isotonic crystalloid 3 ml/kg/h for 1 h before

Initial LVEDP-guided crystalloid:

Pharmacotherapy for ACS Among Patients With CKD

Aspirin

• There is no increased bleeding risk with

aspirin therapy among patients receiving

hemodialysis

• The available data suggest that aspirin

therapy is safe and effective in ACS patients

with CKD and should be used in these patients

to reduce the risk of death and vascular

events

Ethier J et al Aspirin prescription and outcomes in hemodialysis patients: the Dialysis Outcomes and

Practice Patterns Study (DOPPS) Am J Kidney Dis 2007;50:602–611

Clopidogrel vs Placebo

The GUSTO severe bleeding is nonsignificantly higher with clopidogrel than placebo

Dasgupta A et al

Ticagrelor vs Clopidogrel

James S et al Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results

from the Platelet Inhibition and Patient Outcomes (PLATO) trial Circulation 2010;122:1056–1067

Creatinine Clearance vs Major Bleeding Creatinine Clearance vs Primary Outcome

Prasugrel vs Clopidogrel

Wiviott SD et al TRITON-TIMI 38 Investigators Prasugrel versus clopidogrel in patients with acute

coronary syndromes N Engl J Med 2007;357:2001–2015

The glycoprotein (GP) IIb/IIIa receptor

antagonists

• The use of GP IIb/IIIa receptor antagonists in CKD patients with ACS indicate a reduction in ischemic events but overall increase

in the risk of bleeding events

• Eptifibatide and tirofiban can be considered as a treatment

strategy in CKD patients presenting with ACS within follow

dosing recommendations

Melloni C et al Safety and efficacy of adjusted-dose eptifibatide in patients with acute coronary syndromes

and reduced renal function Am Heart J.2011;162:884–892

Medication Renal

Elimination

Dose in Patients Without CKD Dose Adjustment in CKD

Abciximab NS PCI: 0.25-mg/kg bolus followed by infusion

of 0.125 μg·kg−1·min−1 (maximum 10 μg/min) for 12 h after procedure

• No adjustment

Eptifibatide 50 % • ACS: 180-μg/kg bolus followed by an

infusion of 2 μg·kg−1·min−1 for up to 72 h

• PCI: 180 μg/kg followed by continuous infusion of 2 μg·kg−1·min−1 for up to 18–24

h A second 180-μg/kg bolus given 10 min after the first bolus

Tirofiban 65% PCI: 25 μg/kg IV over 3 min followed by an

infusion of 0.15 μg·kg−1·min−1 for up to 18

h post-PCI

CrCl ≤60 mL/min:

• PCI: 25 μg/kg IV over 3 min followed by an infusion of 0.075 μg·kg−1·min−1 for up to 18 h post- PCI

• Patients with CrCl <40 mL/min had higher peak and trough

anti-Xa activity than patients with CrCl ≥40 mL/min and were more likely to have a major hemorrhagic event

Anticoagulant

Becker RC et al Influence of patient characteristics and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in non-ST-segment elevation acute coronary

syndromes Am Heart J 2002;143:753–759

NS •UA/NSTEMI (initial dosing):

Bolus of 60 U/kg (maximum 4000 U) followed by an infusion of 12 U·kg−1·h−1 (maximum 1000 U/h) to maintain aPTT at 1.5–2.0 times control

• STEMI patients receiving fibrinolytic therapy:

Bolus of 60 U/kg (maximum 4000 U/kg) followed by an infusion of 12 U·kg−1·h−1 (maximum 1000 U) initially, adjusted to maintain aPTT at 1.5–2.0 times

control for 48 h or until revascularization

• No adjustment recommended

Enoxaparin 40 % • UA/NSTEMI: 1 mg/kg SC every 12 h

• STEMI patients <75 y of age receiving fibrinolytic therapy: 30-mg single IV bolus plus a 1-mg/kg SC dose followed by 1 mg/kg

SC every 12 h

• STEMI patients ≥75 y of age receiving fibrinolytic therapy: No bolus, 0.75 mg/kg SC every 12 h

CrCl <30 mL/min:

• UA/NSTEMI: 1 mg/kg SC once daily

• STEMI patients <75 y of age receiving fibrinolytic therapy:

30-mg single IV bolus plus a 1-mg/kg

SC dose followed by 1 mg/kg administered SC once daily

• STEMI patients ≥75 y of age receiving fibrinolytic therapy:

No bolus, 1 mg/kg administered SC once daily

Not recommended in dialysis patients

Medication Renal

Elimination

Dose in Patients Without CKD Dose Adjustment in CKD

Fondaparinux 50 % • STEMI patients receiving fibrinolytic

therapy:

2.5 mg IV followed by 2.5 mg SC daily starting the following day

CrCl <30 mL/min:

• PCI: 0.75-mg/kg bolus followed by infusion of 1 mg·kg−1·h−1 for the duration of the procedure

Dialysis:

• PCI28: 0.75-mg/kg bolus followed by infusion of 0.25 mg·kg−1·h−1

3,3%

4,2%

6,2%

2,1%

In the subgroup of patients with

CrCl <30 mL/min, the rates of major bleeding

at 9 days were significantly lower in the

group receiving fondaparinux

The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators Comparison of fondaparinux

and enoxaparin in acute coronary syndromes N Engl J Med 2006;354:1464–1476

p=0.001

Chew DP et al Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients with renal impairment undergoing percutaneous coronary intervention (a subanalysis of the REPLACE-2 trial)

Am J Cardiol 2005;95:581–585

Event rates and odds ratios for bivalirudin versus heparin/ GP IIb/IIIa inhibition with respect to (A) 30-day death, MI, or urgent revascularization (B) protocol-defined major hemorrhage

(C) TIMI major or minor hemorrhage

Bivalirudin versus heparin+GP IIb/IIIa

inhibition

β-Blockers

• β-Blocker use was associated with a 40% relative reduction in mortality among those undergoing dialysis and a 56% relative

reduction among those without ESRD (p<0.001 )

• The data from randomized and observational studies support the routine use of β-blocker therapy in CKD patients presenting with ACS when no contraindications are present

• Dose adjustment for atenolol is 50 mg once daily for 15–35 mL/min and 25 mg once daily for CrCl <15 mL/min

Berger AK et al Aspirin, beta-blocker, and angiotensin- converting enzyme inhibitor therapy in patients with

end-stage renal disease and an acute myocardial infarction J Am Coll Cardiol 2003;42:201–208

ACE inhibitor/ARB

• Practically, the use of ACE inhibitors or ARBs can be considered

in patients with CKD as long as the SCr does not increase beyond

> 2.5 mg/ dL and the serum potassium remains <5.5 mEq/L

• The use of ACE inhibitors or ARBs in patients undergoing

chronic dialysis has been associated with an increased risk of

hyperkalemia

Ronco C et al Cardiorenal syndrome J Am Coll Cardiol 2008;52:1527–1539

Garthwaite E et al The effects of angiotensin converting enzyme inhibitors on potassium homeostasis

in dialysis patients with and without residual renal function Artif Organs 2009;33:641–647

Aldosterone Receptor Antagonists

•Serious hyperkalemia (≥6.0 mEq/L) occurred in 5.5% of patients receiving eplerenone compared with 3.9% in the placebo group

(p=0.002)

•AHA guidelines recommend against using aldosterone blockade

if significant renal dysfunction (SCr >2.5 mg/dL in men and >2.0 mg/dL in women) or hyperkalemia (serum potassium >5.0

• Patients with renal dysfunction not taking statins were at significantly increased risk of in-hospital and 1-month major adverse cardiovascular events and cardiac death at 1 year

Statins

Lim SY et al Korea Acute Myocardial Infarction Registry Investigators Effect on short- and long-term major adverse cardiac events of statin treatment in patients with acute myocardial infarction and renal

dysfunction Am J Cardiol 2012;109:1425–1430

Statin vs No Statin in CKD with AMI

Lim SY et al Korea Am J Cardiol 2012;109:1425–1430

MACE (death, myocardial infarction, and target lesion revascularization)

Summary

• The medications routinely used in all patients CKD presenting with ACS need important considerations to provide the greatest benefit while limiting the chance for harm

• These would include careful assessment of renal function, use of a validated equation for dose adjustment of medications, avoidance of medications that are contraindicated in patients with stage 4 and 5 CKD

•CIN Prevention with the use of PCI

•Fibrinolytic therapy be considered as a treatment strategy for CKD patients presenting with STEMI when primary PCI is not available with careful consideration of intracranial hemorrhage

Summary

considered in CKD patients presenting with ACS

• Glycoprotein IIb/IIIa receptor antagonist and Anticoagulant can

be considered as a treatment strategy in CKD patients presenting with ACS within dosing modifications and exclusions for each agent

• ACE inhibitor/ARB and Aldosterone blocker should be considered

in CKD patients presenting with ACS and LV dysfunction with

potassium and SCr monitoring closely

Thank you very much

cảm ơn rất nhiều