Management of a Patient with

Chronic Kidney Disease and

STEMI
Nicolas Meneveau, MD, PhD, FESC
University Hospital Jean Minjoz
Besanon - 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/m
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

Mid LAD : TIMI 1 flow

BMS : 2.5 mm diameter & 18 mm length

Coronary Angiogram and

Primary Angioplasty

Kissing balloon inflation

Final result

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 g/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 g/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
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

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

Why did our Patient bleed ?

Excess Dosing of Antithrombotic therapy
Underdosed

Dose Group
Recommended
Mild Excess

Major Excess

35
30
25
20

Factors
associated
with excess
dosingbe
:
In
30%
ourofcase
major
: consider
bleeding
reduction
may
older age, female sex, renal insufficiency,
of
attributable
bivalirudintoinfusion
excessrate
dosing
to 1
low body weight, diabetes, and CHF
and require
mg/kg/hr
dose adjustment

15
10
5
0

UFH

LMWH

GP IIb/IIIa

Alexander JAMA 2004;294:3108-16.

Bleeding Risk Evaluation

Why did Our Patient Experience Stent

Thrombosis ?

Impact of Discontinuation of Antithrombotic Therapy on

In-Hopital Mortality & Stent Thrombosis

In-hospital mortality (GRACE)

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

Stent thrombosis (e-Select)

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

CKD Patients Have Poorer Prognosis Compared

with Those with Normal Renal Function
- Even
35-40%
mild
of ACS
renalpts
disease
have should
some degree
be considered
of renal insufficiency
a major risk
- CV disease factor
is the for
leading
CV complications
cause of death
after
in pts
MI with CKD

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

Pts with CKD Presenting with MI Receive

Fewer Evidence-Based Therapies
Acute In-Hospital Medications

STEMI

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

P2Y12 Receptor Antagonists in Patients with

Chronic Kidney Disease

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

Ticagrelor in ACS and Renal Dysfunction

Benefits of Ticagelor are larger in pts with CKD without any need for
dose reduction to prevent major bleeding.
0.25

0.25

KM curves for major bleeding

KM curves for CV death/MI/stroke

0.20

0.20

0.15

0.15

0.10

0.10

0.05

0.05

0.00

0.00
0

60

120

180

240

300

360

60

Days since randomisation

120

180

240

300

360

Days since randomisation

Creatinine Clearance Treatment :

<60 Ticagrelor
60 Ticagrelor

<60 Clopidogrel
60 Clopidogrel

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

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

Major bleeding events (%)

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

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

Anticoagulant Therapy in CKD Pts

with STEMI Treated with PCI :
Bivalirudin and the HORIZONS-AMI Trial
30-day outcomes

CrCl 60 ml/min

CrCl < 60 ml/min

NACE
MACE
Death

MI
Ischemic TVR
Major bleeding
0

Bival better

UFH + GPI better

Bival better

UFH + GPI better

NACE : net adverse cardiac event (death, reinfarction, ischemiaSaltzman AJ et al. JACC Intv 2011;4:1011-9.
driven TVR, stroke or non-CABG-related major bleeding)

Safety of Bivalirudin in Pts with Renal Impairment

Undergoing PCI : REPLACE-2 & ACUITY Trials

TIMI major or minor hemorrhage in

REPLACE-2 trial
Chew DP et al. Am J Cardiol 2005;95:581585

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

Non-CABG-related major bleeding

Non-CABG-related major
& minor bleeding
White HD et al. Am Heart J 2009;157:125-31.

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

Major Bleeding is Associated with a

Subsequent Increase in Late Mortality
Pooled Analysis of OASIS Registry, OASIS2, CURE

Cumulative Events, percent

14

12.8%

12

Bleeding

10
8

5-fold risk

HR=5.37 [3.97-7.26]

No Bleeding

2.5%

2
0

10

15

Days

20

Eikelboom JW et al.

25

30

Circulation 2006;114: 774 - 782

Blood Transfusion Increased 30-Day Mortality

GUSTO IIb, PURSUIT, PARAGON B
(n=24,111; 10% transfused)

Survival Rates

No Transfusion
Transfusion*
0.98

Aggressive use of blood transfusion

in stable pts cannot be
recommended

0.96

0.94

0.92

0.9
0

10

15

20

25

30

35

Days
* When administered for a nadir of haematocrit > 25%

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

Impact of Discontinuation of Antithrombotic Therapy on

In-Hopital Mortality & Stent Thrombosis

In-hospital mortality (GRACE)

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

Stent thrombosis (e-Select)

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

Impact of Low Platelet Response to Clopidogrel in

CKD Pts Undergoing PCI
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

Morel O et al. JACC 2011;57:399408.

Risk Score for Non-CABG-Related

TIMI Major Bleeding Within 30 Days of PCI
+8

Risk score

<10

Major bleed*
(%)

+9
+5

0.6%
+1

10-14

1%

15-19

2%

20

4.8%

+6

-6
23

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