Management of a Patient with

Chronic Kidney Disease and

STEMI

Nicolas Meneveau, MD, PhD, FESC

University Hospital Jean Minjoz

Besançon - France

Conflict of Interest

• Research grant : GlaxoSmithKline, St Jude Medical,

• Speaker : Boehringer Ingelheim, Daiichi-Sankyo/Lilly,

Novartis, Sanofi-Aventis, Servier, The Medicines

Company, Astra Zeneca, Edwards Life Science

• Consulting : St Jude Medical, Edwards Life Science,

Clinical Case

• 75 year old female

• Called the mobile emergency medical service for chest pain lasting

for 2.5 hrs

• Cardiovascular risk factors

– Hypertension

– Hypercholesterolemia

– Family history of CAD

• Consulted a nephrologist 5 years ago for polycystic kidney disease.

Annual monitoring was recommended. Never saw another

nephrologist since.

• Medication :

– Statin : atorvastatin 10 mg daily

– ACE inhibitor : ramipril 10 mg daily

– Beta blocker : atenolol 50 mg daily

First Medical Contact

• Clinical examination :

– SBP = 135 mmHg; HR = 68 bpm; no signs of heart failure

– Height=156 cm; weight=48 kg; BMI=20 kg/m²

• ECG :

Pre-Hospital Management

• IV opioids : 4-8 mg morphine

• Aspirin : 250 mg orally

• Clopidogrel : 600 mg loading dose

• IV bolus of 3000 IU UFH without infusion

• Fast transportation to the cathlab for primary angioplasty

– Transportation time = 45 min

– Time from FMC to arrival in the cathlab = 195 min

– Persistent chest pain & unchanged ECG

• Arrival in the cathlab : ACT = 182 s

– Bivalirudin : I.v. bolus of 0.75 mg/kg followed by an infusion of

1.75 mg/kg/h (discontinued at the completion of PCI)

Coronary Angiogram and

Primary Angioplasty

BMS : 2.5 mm diameter & 18 mm length Mid LAD : TIMI 1 flow

Coronary Angiogram and

Primary Angioplasty

Final result Kissing balloon inflation

Initial In-Hospital Course

• Discontinuation of bivalirudin at the completion of PCI, aspirin 75 mg

daily, clopidogrel 75 mg daily

• Initial blood sample results :

– CrCl : 29 mL/min, Haemoglobin : 12.1 g/dL, Troponin : 65 µg/L, BNP

: 185 pg/mL

• Echocardiography : LVEF = 51%

• Day 2 : maelena associated with shock (SBP = 75 mmHg) and drop in

haemoglobin level from 12.1 to 7.1 g/dL

– Transfusion of 2 units of RBC and use of vasopressive drugs

• Endoscopic diagnosis of peptic ulcer bleeding

– Local endoscopic treatment, discontinuation of aspirin and initiation

of IV proton pump inhibitors

• Day 5 : recurrent chest pain related to repeat anterior STEMI

Repeat Coronary Angiogram :

Sub Acute Stent Thrombosis

Stent thrombosis Thromboaspiration,

Aspirin (250 mg),

I.v. bolus UFH (60 IU/kg)

Final result

Course until Discharge

• Aspirin resumed during repeat PCI and continued thereafter

• Uneventful course until discharge :

– Additional reduction in LVEF = 45%

– Cr Cl : 28 mL/min, Haemoglobin : 9.8 g/dL, Troponin : 76 µg/L, BNP :

204 pg/mL

• VASP index = 39% (good responder to clopidogrel)

• Medication at discharge :

– Dual antiplatelet therapy : aspirin and clopidogrel 75 mg daily

– ACE inhibitor : ramipril 10 mg daily

– Beta blocker : atenolol 50 mg daily

– Statin : atorvastatin 80 mg daily

Why did Our Patient Bleed ?

Why did our Patient bleed ?

Predictors of Major Bleeding in PCI

Feit F, Voeltz MD, Attubato MA, et al. Am J Cardiol 2007

Baseline risk factors

Age ≥ 75

Gender (Female)

Creatinine Clearance (per g/dl increase)

Lower body weight

Anemia

Peri-procedural risk factors

Treatment Group (Heparin + GPI vs. bivalirudin)

Provisional GPI received

Procedure Duration >1h

Time to Sheath Removal >6h

Intensive Care Unit stay (days)

Intra-aortic Balloon Pump

1 2 3 4

0

5

10

15

20

25

30

35

Underdosed Recommended Mild Excess Major Excess

UFH LMWH GP IIb/IIIa

Alexander JAMA 2004;294:3108-16.

Why did our Patient bleed ?

Excess Dosing of Antithrombotic therapy Dose Group

Factors associated with excess dosing :

older age, female sex, renal insufficiency,

low body weight, diabetes, and CHF

30% of major bleeding may be

attributable to excess dosing

and require dose adjustment

In our case : consider reduction

of bivalirudin infusion rate to 1

mg/kg/hr

Bleeding Risk Evaluation

Why did Our Patient Experience Stent

Thrombosis ?

Impact of Discontinuation of Antithrombotic Therapy on

In-Hopital Mortality & Stent Thrombosis

Urban P et al. JACC 2011;57:1445-54.

In-hospital mortality (GRACE) Stent thrombosis (e-Select)

Spencer FE et al Circulation 2007;116:2793-2801.

CKD Patients Have Poorer Prognosis Compared

with Those with Normal Renal Function

Anavekar NS. N Engl J Med 2004;351:1285-95.

- 35-40% of ACS pts have some degree of renal insufficiency

- CV disease is the leading cause of death in pts with CKD

Even mild renal disease should be considered a major risk

factor for CV complications after MI

Fox Cs et al. Circulation 2010;121:357-65.

Acute In-Hospital Medications STEMI

Pts with CKD Presenting with MI Receive

Fewer Evidence-Based Therapies

P2Y12 Receptor Antagonists in Patients with

Chronic Kidney Disease

Capodanno D et al. Circulation 2012;125:2649-61.

Ticagrelor in ACS and Renal Dysfunction

James S et al. Circulation 2010;122:1056-67.

Creatinine Clearance – Treatment : <60 – Ticagrelor <60 – Clopidogrel

≥60 – Ticagrelor ≥60 – Clopidogrel

0.25

0.20

0.15

0.10

0.05

0.00

0 60 120 180 240 300 360

Days since randomisation

0 60 120 180 240 300 360

Days since randomisation

0.25

0.20

0.15

0.10

0.05

0.00

KM curves for major bleeding KM curves for CV death/MI/stroke

Benefits of Ticagelor are larger in pts with CKD without any need for

dose reduction to prevent major bleeding.

Influence of Renal Dysfunction on the Use of

GP IIb/IIIa Inhibitors in ACS Pts

• Investigations of IIb/IIIa inhibitors in pts with renal dysfunction are limited

• 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 [0.12-0.98]; p=0.04

– Increased bleeding events : OR = 2.13 [1.39-3.27]; p<0.0001

Freeman RV et al. JACC 2003;41:718-24.

Maj

or

ble

ed

ing

eve

nts

(%

)

Anticoagulant Therapy in CKD Pts

with STEMI Treated with PCI :

Bivalirudin and the HORIZONS-AMI Trial

1 2

Bival better UFH + GPI better

0 1 2

NACE

Death

MI

Ischemic TVR

Bival better UFH + GPI better

Major bleeding

MACE

0

Saltzman AJ et al. JACC Intv 2011;4:1011-9.

CrCl < 60 ml/min CrCl ≥ 60 ml/min

NACE : net adverse cardiac event (death, reinfarction, ischemia-

driven TVR, stroke or non-CABG-related major bleeding)

30-day outcomes

Safety of Bivalirudin in Pts with Renal Impairment

Undergoing PCI : REPLACE-2 & ACUITY Trials

Chew DP et al. Am J Cardiol 2005;95:581–585

TIMI major or minor hemorrhage in

REPLACE-2 trial

Multivariable predictors of major

bleeding at 30 days among pts with renal

insufficiency in ACUITY trial

Mehran R et al. JACC Intv 2009;2:748-57.

Safety of a single IV bolus of Enoxaparin compared

with UFH in Pts with Renal Impairment Undergoing PCI

The STEEPLE Trial

White HD et al. Am Heart J 2009;157:125-31.

Non-CABG-related major bleeding Non-CABG-related major

& minor bleeding

Recommendations for Clinical Practice

• The choice and dose of antithrombotic drugs need to be carefully evaluated in pts

with CKD and STEMI in order to limit overdosing

• No P2Y12 receptor antagonist requires dose adjustment. Ticagrelor yielded larger

benefits in pts with poor renal function, without any excess in bleeding

• LMWH, bivalirudin and GPIIb/IIIa blockers are cleared by the kidneys and may

require dose adjustment

• UFH remains the anticoagulant of choice in pts with CrCl<30 mL/min, but does not

totally protect against bleeding complications

• Renal function is rarely known in the acute phase of MI : same 1st line AT therapy

– Choose shortest possible duration of AC therapy that can be stopped after PCI

– Bivalirudin and IV bolus of enox lower bleeding rate with same anti-ischemic

efficacy

• Further RCTs warranted since most recomandations based on single-center data or

post-hoc analysis (CKD pts were excluded from 75% of CAD randomized trials)

Back-up Slides

In-Hospital Mortality

All-Cause Mortality at 30 Days

0

2

4

6

8

10

12

14

Cu

mu

lati

ve E

ven

ts, p

erce

nt

Days

Eikelboom JW et al. Circulation 2006;114: 774 - 782

5-fold risk

HR=5.37 [3.97-7.26]

0 10 15 20 5 25 30

Bleeding

No Bleeding

12.8%

2.5%

Major Bleeding is Associated with a

Subsequent Increase in Late Mortality

Pooled Analysis of OASIS Registry, OASIS2, CURE

Blood Transfusion Increased 30-Day Mortality GUSTO IIb, PURSUIT, PARAGON B

(n=24,111; 10% transfused)

Rao SV et al. JAMA 2004;292:1555-62.

0.9

0.92

0.94

0.96

0.98

1

0 5 10 15 20 25 30 35

Days

Su

rviv

al R

ate

s

No Transfusion

Transfusion*

* When administered for a nadir of haematocrit > 25%

Aggressive use of blood transfusion

in stable pts cannot be

recommended

Impact of Discontinuation of Antithrombotic Therapy on

In-Hopital Mortality & Stent Thrombosis

Urban P et al. JACC 2011;57:1445-54.

In-hospital mortality (GRACE) Stent thrombosis (e-Select)

Spencer FE et al Circulation 2007;116:2793-2801.

Impact of Low Platelet Response to Clopidogrel in

CKD Pts Undergoing PCI

Morel O et al. JACC 2011;57:399–408.

• Low-responder rate similar in CKD and non CKD pts

• Presence of low platelet response to clopidogrel in CKD pts is

associated with worse outcomes after PCI

Risk Score for Non-CABG-Related

TIMI Major Bleeding Within 30 Days of PCI

Mehran R. JACC Cardiovasc Interv 2011;4:654-64.

Risk score Major bleed*

(%)

<10 0.6%

10-14 1%

15-19 2%

20 4.8%

+8

+9

+5

+1

+6

-6

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