Long-Term Outcomes in Patients Undergoing Coronary Stenting on Dual Oral Antiplatelet Treatment...

Long-Term Outcomes in Patients Undergoing Coronary Stenting on Dual Oral Antiplatelet Treatment Requiring Oral

Anticoagulant Therapy

R. Rossini, G. Musumeci, C. Lettieri*, M. Molfese**, L. Mihalcsik, P. Mantovani**, V. Sirbu, T. A. Bass***, F. Della Rovere**,

A. Gavazzi, D. J Angiolillo***

Dipartimento Cardiovascolare, Ospedali Riuniti di Bergamo*Ospedale Carlo Poma, Mantova

**Ospedale Galliera, Genova*** University of Florida, Jacksonville, US

American Journal of Cardiology 2008; 102: 1618-1623

Background

In patients undergoing coronary stenting, long-term dual antiplatelet therapy with aspirin and

clopidogrel reduces atherothrombotic events but also increases the risk of bleeding. The potential for

developing bleeding complications is further enhanced in patients also requiring oral

anticoagulant treatment (“triple therapy”).

Dipartimento CardiovascolareClinico e di RicercaOspedali RiunitiBergamo


Aim

To assess long-term outcomes associated with the use of

triple-therapy in patients undergoing coronary stenting and

evaluate how these may be affected by targeting

international normalized ratio (INR) values to the lower

therapeutic range.



We analyzed 102 consecutive patients undergoing coronary stenting treated with dual antiplatelet therapy also requiring oral anticoagulation. The target international normalized ratio (INR) value was 2-2.5

An age and sex-matched control group (n=102) with similar disease presentation and procedure type was selected from the study period

18 months Follow-up:- TIMI major and minor bleedings- MACE: death, myocardial infarction, stent thrombosis, stroke and target vessel revascularization

Methods

Baseline CharacteristicsBaseline Characteristics

Age (y) 67.9 9.3

Male 82 (80.4%)

UA/NSTEMI 45 (44.1 %)

STEMI 35 (34.3 %)

Stent/Pt 1.5±0.7

Pt with DES 48 (47%)

Target INR value 2-2.5

Age (y) 67.9 9.3

Male 82 (80.4%)

UA/NSTEMI 45 (44.1 %)

STEMI 35 (34.3 %)

Stent/Pt 1.5±0.7

Pt with DES 48 (47%)

Target INR value 2-2.5



68.2 8.1 0.2

81 (79.4 %) 0.8

46 (45 %) 0.6

35 (34.3 %) 0.9

1.5±0.9 0.8

49 (48%) 0.4

68.2 8.1 0.2

81 (79.4 %) 0.8

46 (45 %) 0.6

35 (34.3 %) 0.9

1.5±0.9 0.8

49 (48%) 0.4

( n = 102 )

P value

( n = 102 )

Triple Controls

Main Indications for Warfarin useMain Indications for Warfarin use

Mean duration of triple therapy was 158 days (range 30-540)

66,6

17,6

4,9 4,9 5,8

0

20

40

60

80

100

AF LVthrombus

LVaneurism

Pulmonaryembolism

other

%



Results: 18-month Major and Minor BleedingResults: 18-month Major and Minor BleedingDipartimento CardiovascolareClinico e di RicercaOspedali RiunitiBergamo


Mean INR at the time of bleeding was 3.1±0.7

2,9

7,8

22,9

0

5

10

15

Major bleeding Minor bleeding

triple therapy dual therapy%

P=0.6

P=0.1

Triple therapy (n=102)

Dual therapy (n=102)

p-value

Major bleedings, n (%) Intracranial bleeding, n (%) Gastrointestinal bleeding, n (%) Groin haematoma, n (%) Urinary bleeding, n (%)

3 (2.9)0

1 (1)1 (1)1 (1)

2 (2)0

1 (1)1 (1)

0

0.6NSNSNSNS

Minor bleedings Gastrointestinal bleeding, n (%) Groin haematoma, n (%) Epistaxis, n (%) Decrease in the blood haemoglobin, n (%) Urinary bleeding, n (%)

8 (7.8)1 (1)1 (1)1 (1)2 (2)

3 (2.9)

3 (2.9)0

1 (1)1 (1)1 (1)

0

0.1NSNSNSNSNS

The optimal ROC-defined INR value cut point between sensitivity and specificity for all bleeding was 2.6.

This cut-off value had a specificity of 89%, a sensitivity of 66%, a negative predicted value of 95%, and a positive predictive value of 44%.

0,00

0,25

0,50

0,75

1,00

0,00 0,25 0,50 0,75 1,00

ROC Curve of ALLBLED

1-Specificity

Sensitiv

ity

Criterions

NUOVA63

Specificity

All bleeding cumulative distribution

100

90

80

70

60

500 200 300 450 600

%

Double therapy

Triple therapy

P=0.13

95.1 %

89.2 %

Days

Ble

edin

g ev

ent

free

sur

viva

l



100

90

80

70

60

500 200 300 450 600

%

Double therapy

Triple therapy with INR < 2.6

All bleeding cumulative distribution by INR

95.1 %

95.1 %

Days

Ble

edin

g ev

ent

free

sur

viva

l

Triple therapy with INR ≥ 2.6

66.7 %

†

‡

† P<0.0001 vs Double therapy

‡ P<0.0001 vs Triple with INR <2.6



In the triple therapy group, use of GPIIb/IIIa blocker (OR 2.7, P = 0.03), value of INR > 2.6 (OR 9.8, P = 0.0007), female gender (OR 2.0, P = 0.04), and smoking (OR 2.9, P = 0.02), were significant predictors of any bleeding at 18 months in univariate analyses

Multivariable analysis showed that only an INR > 2.6 predicted overall bleeding (OR 19.2, 95% CI 4.3-44.6; P=0.0003).

18-month MACE18-month MACEDipartimento CardiovascolareClinico e di RicercaOspedali RiunitiBergamo


5,84,9

0

5

10

15

20triple therapy dual therapy

%

P=0.7

Conclusions

In high risk patients implanted with coronary stent,

long term triple therapy seems to be safe and effective.

Careful monitoring and low target of INR must be provided in these patients



Long-Term Outcomes in Patients Undergoing Coronary Stenting on Dual Oral Antiplatelet Treatment...

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