USE OF CITRATED CLOTTING TIME IN MONITORING ENOXAPARIN LEVEL DURING CONTEMPORARY PERCUTANEOUS CORONARY INTERVENTION IN ACUTE CORONARY SYNDROMES

B.Y.C. Cheong, MD, MRCP(UK), L. O’Meallie, MD, FACC, FSCAI, J.G. Diez, MD, FACC, FSCAISection of Cardiovascular Medicine, Tulane University Health Science Center, New Orleans, Louisiana

INTRODUCTION

OBJECTIVE

METHODS

INTRODUCTION SAFETY & EFFICACY VARIABLES

RESULTS

OBJECTIVES

METHODS

CONCLUSIONS

Heparin is pivotal during percutaneous coronary intervention [PCI]. Recently updated ACC/AHA guidelines recommended low molecular weight heparin [LMWH] or unfractionated heparin [UFH] as the anticoagulants of choice for management of acute coronary syndrome [ACS].

LMWH is a better anticoagulant than UFH from a theoretical and pharmacological point of view. However, some interventionalists are cautious about using LMWH due to the lack of bedside testing.

Data are accumulating suggesting that LMWH, especially enoxaparin, is safe and effective during elective PCI. In ACS (SYNERGY) there appear to be slightly higher rates of bleeding.

Recently approved point-of-care ENOX™ test provides a Citrated Clotting Time [CCT] for enoxaparin, enabling the level of anticoagulation to be determined within 5 minutes.

The ELECT trial suggested a therapeutic range of 250-450 secs. The ENOX™ test label suggest ≥ 260 secs as therapeutic.

To assess the safety and efficacy profile of using enoxaparin during elective an emergent PCI when monitored by CCT.

Cohort analysis of prospective patients presented to a tertiary university hospital for PCI.

Baseline CCT was measured [≥ 260 s corresponds anti-Xa level of 1.0 IU/mL]. Those with CCT < 260 s will receive a booster IV enoxaparin bolus of 0.3 mg/kg with CCT repeated 10 mins later. The following groups are identified:-

I) Patients received enoxaparin 1 mg/kg IV and CCT ≥ 260s

II) Patients received ≥ 3 doses of enoxaparin SC and CCT ≥ 260s

III) Patients with <3 doses of SC enoxaparin and needed a supplementary 0.3 mg/kg of enoxaparin IV

Patients all received dual oral anti-platelet therapy, eptifibatide, and stenting at the appropriate lesions.

Closure devises were employed in the majority of patients.

TIMI major and minor bleeding rate

Vascular complications

Procedural success rate

The 30-day composite endpoint of death, recurrent MI or repeat revascularization

Hematological derangements: decrease in Hb, platelet count, transfusions, and combination.

There were a total of 77 patients [49 patients with ACS].

Demographic data are shown in Table 1.

VARIABLESALL

( N = 77)

ACS Group

( N = 49 )

ELECTIVE Group ( N = 28 )

Age (yrs) 57.8 ± 10.4 59.1 ± 10.4 55.7 ± 10.3

Male (%) 46 32 14

CAD (%) 51.4 38 76

HTN (%) 76.7 76.6 76.9

DM (%) 31.9 23.8 38.5

LIPIDS (%) 83 77.3 92

SMOKING Hx (%) 43.1 52.5 28

STEMI (N) 18

NSTEMI (N) 24

USA (N) 7

The change in hemoglobin level and platelet counts within 48 hours after PCI are shown in Table 2.

VARIABLES ALL ACS Group ELECTIVE Group

Hb (g/dL) - PRE 13.7 ± 1.6 14.1 ± 1.6 13.1 ± 1.5

Hb (g/dL) - POST 12.1 ± 1.7 12.2 ± 1.9 12.0 ± 1.4

Mean Hb (g/dL) -1.6 ± 1.4 -1.9 ± 1.3 -0.9 ± 1.4

Plts (x103) - PRE 232 ± 72 229 ± 61 238 ± 94

Plts (x103) - POST 205 ± 61 201 ± 59 213 ± 67

Mean Plts (x103) -26 ± 36 -26 ± 32 -27 ± 43

0

175

350

525

700

B-IV P-IV P-SC>3 B-SC/IV P-SC/IV

Cit

rate

d C

lott

ing

Tim

e (

se

cs

)

Citrated Clotting Time of various subgroups and in patients presenting for emergent and elective PCI are shown in Graphs 1A and 1B.

GRAPH 1A B-IV: Baseline CCT in pts who have not receive any IV enoxaparin

P-IV: CCT 10 mins after IV enoxaparin

P-SC>3: CCT in pts with received 3 doses of enoxaparin SC

B-SC/IV: Baseline CCT who received < 3 SC doses of enoxaparin

P-SC/IV: CCT 10 mins after 0.3 mg/kg of enoxaparin IV booster dose

P < 0.001

0

175

350

525

700

B-ACS P-ACS B-ElectiveP-Elective

Cit

rate

d C

lott

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cs

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GRAPH 1B B-ACS: CCT at baseline in pts with ACS

P-ACS: Peak CCT in pts with ACS

B-Elective: Baseline CCT in pts presented for elective PCI

P-Elective: Peak CCT in pts presented for elective PCI

Table 3 illustrates the procedural success and complication rates. Graph 2 compares the TIMI bleeding rates between this study and other PCI studies using enoxaparin.

VARIABLES (%) ALL ACS Group ELECTIVE Group

In-Hospital Death 0 0 0

Procedural Success Rate

97.4 98 96.4

30-day Composite End-Point *

1.3 0 3.6

Vascular Complication 5.2 # 8.2 # 0

* MI, death, urgent revascularization# 2 hematomas; 1 arterio-venous fistulae; 1 hemopericardium

NICE-1

NICE-4

Collet et al.

ELECT

Cheong et al. [ACS pts]

A to Z

Synergy-Non CABG

0

1

2

3

4

5

6

7

TIMI BLEEDING

TIMI Major TIMI Minor

Table 2.

Table 1.

Table 3.

Graph 2.

Our study demonstrated that the level of anticoagulation by enoxaparin can be effectively measured by the Citrated Clotting Time.

1 mg/kg IV bolus of enoxaparin in patients who have not received any anticoagulation, or a supplementary IV dose of 0.3 mg/kg in patients with CCT < 260 secs and are already receiving SC enoxaparin, will achieve adequate anticoagulation levels for PCI.

Use of enoxaparin during PCI is associated with high procedural success rate during both urgent and elective settings with acceptable level of bleeding rates when compared with other contemporary trials of PCI using enoxaparin. The rate of bleeding events in the ACS group is higher than in elective cases.

The CCT documented effective anticoagulation after IV enoxaparin administration at 1mg/kg single bolus, and with 0.3 mg/kg “booster” dose.

The levels of CCT obtained had a higher dispersion than previously reported.

In the ACS group there was a trend towards a higher rate of bleeding despite achieving similar CCT times when compared to patients undergoing elective PCI. All the ACS patients received concomitant ASA, clopidogrel and eptifibatide. Half of the ACS group was already on SC enoxaparin.