e. di lorenzo a.o.r.n. “s. g. moscati” – avellino - italy long-term outcome of drug-eluting...

E. Di Lorenzo A.O.R.N. “S. G. Moscati” – Avellino - Italy

LONG-TERM OUTCOME OF DRUG-ELUTING STENTS

COMPARED WITH BARE METAL STENTS IN ST-SEGMENT

ELEVATION MYOCARDIAL INFARCTION

Results of the Paclitaxel- or Sirolimus-Eluting Stent Versus Bare

Metal Stent in Primary Angioplasty (PASEO) Randomized Trial

Emilio Di Lorenzo1, Rosario Sauro1, Attilio Varricchio1, Giannignazio Carbone1, Giuliana Cortese2, Michele

Capasso1, Tonino Lanzillo1, Fiore Manganelli1, Ciro Mariello1, Francesco Siano1, Maria Rosaria Pagliuca1,

Giovanni Stanco1, Giuseppe Rosato1, Giuseppe De Luca3

1Department of Cardiology and Cardiovascular Surgery, A.O.R.N. S.G. Moscati, Avellino, Italy

2Department of Statistical Sciences, University of Padova, Italy

3Division of Cardiology, Ospedale “Maggiore della Carità,” Eastern Piedmont University, Italy.


BACKGROUND

Routine stent implantation has been advocated for patients with acute myocardial infarction (MI) referred for primary angioplasty, with superior results compared to balloon dilation. (Stone GW et al N Engl J Med. 2002;346:957–966) (Keeley EC et al Lancet 2003; 361: 13-20) (Antoniucci D et al Circulation. 2004;109: 1704–1706)

However, the late clinical efficacy is still hampered by the occurrence of in-stent restenosis and the need for repeat intervention. (Suryapranata H, Heart. 2005; 91:641– 645) (De Luca G et al Int J Cardiol. 2008;126:37– 44)

Several randomized trials have shown that drug-eluting stents (DES) are associated with a significant reduction in restenosis and TVR in both elective and STEMI patients compared with BMS (Kastrati A et al Eur Heart J. 2007;28:2706 –2713) (De Luca G et al Int J Cardiol. 2009;133:213–222)

No data have been reported on long-term results of DES compared with BMS in STEMI patients


The Paclitaxel or Sirolimus-Eluting Stent Versus Bare Metal

Stent in Primary Angioplasty (PASEO) randomized trial

evaluates the benefits of sirolimus-eluting stents (SES) and

paclitaxel-eluting stents (PES) compared with bare metal

stents (BMS) in patients undergoing primary angioplasty for

STEMI at short- and long-term follow-up.

AIM OF THE STUDY


STUDY DESIGN

Inclusion criteria: chest pain lasting >30 minutes, ST-segment elevation of >1 mm in >2 contiguous ECG leads or with presumably new left bundle-branch block, and hospital admission within 12 hours from symptom onset.

Open-label randomization was performed in the catheterization laboratory after initial angiography by the treating physician when eligibility criteria were met.

Exclusion criteria: active internal bleeding or a history of bleeding diathesis within the previous 30 days; a history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; known allergy to sirolimus, paclitaxel, heparin, aspirin, or clopidogrel; a history of stroke within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; history, symptoms, or findings suggestive of aortic dissection; thrombolytic/fibrinolytic therapy within 24 hours; history of thrombocytopenia; and hemorrhagic retinopathy; Patients on warfarin or acenocoumarol with an international normalized ratio >2, pregnant patients and a vessel site <2.25 mm.


STUDY DESIGN

323 STEMI PATIENTS ASSESSED FOR ELIGIBILITY

53 patients excluded because of exclusion criteria or refusal

to partecipate

270 PATIENTS FINALLY RANDOMIZED

90 ASSIGNED TO Bare Metal Stent

(BMS)

90 ASSIGNED TO Paclitaxel Eluting

Stent (PES)

90 ASSIGNED TO Sirolimus Eluting

Stent (SES)


Primary end point: Target lesion revascularization (TLR) at the 1-year follow-up.

Secondary end points Death and/or reinfarction In-stent thrombosis defined according to the Academic Research

Consortium definition Major adverse cardiac events (MACEs) (combined death and/or reinfarction

and/or TLR) at the long-term (up to 4 to 6 years) follow-up.

All deaths were considered cardiac unless an unequivocal noncardiac cause could be identified.

Recurrent MI was defined as recurrence on anginal symptoms with typical ECG changes and an increase above the upper limit of normal of creatine kinase-MB or troponin.

The indication for a second intervention had to be substantiated by symptoms or by ECG or scintigraphic evidence of ischemia at rest or during exercise.

Subsequent revascularization of other coronary arteries did not constitute an end point.

All events were reviewed by 2 cardiologists blinded to treatment assignment.

END POINTS


VariableBMS

(n = 90)PES (n = 90)

P ValueSES

(N = 90)P value

Agemedian [95% CI]

62 + 17 63 + 15 1.0 62 + 15 1.0

Male Gender (%) 71.1 68.9 1.0 71.1 1.0

Hypertension (%) 24.4 26.7 1.0 27.8 1.0

Diabetes (%) IDDM (%) NIDDM (%)

25.68.9

16.7

23.37.8

15.61.0

27.88.9

17.81.0

Smoking (%) 26.7 24.4 1.0 24.4 1.0

Previous MI (%) 12.2 14.4 1.0 15.6 1.0

Previous CABG (%) 6.7 7.8 1.0 5.6 1.0

Previous PCI (%) 4.4 3.3 1.0 6.7 1.0

Cardiogenic shock (%) 15.6 16.7 1.0 14.4 1.0

Anterior MI (%) 50 51.1 1.0 53.3 1.0

Ejection Fraction < 40% (%) 36.7 38.9 1.0 34.4 1.0

Ischemia time (min) 292 + 222 258 + 192 0.65 264 + 198 0.8

Door-to-balloon time (min) 44.4 + 13.5 43.2 + 14.2 1.0 45.2 + 16.9 1.0

Baseline demographic and clinical characteristics of the three groups of patients


VariableBMS

(n = 90)PES (n = 90)

P ValueSES

(N = 90)P value

IRA LAD (%) LCX (%) RCA (%)

5023.326.7

51.125.623.3

1.053.323.323.3

1.0

Preprocedural TIMI flow 0-1 (%) 2 (%) 3 (%)

75.611.113.3

77.810

12.21.0

78.98.9

12.21.0

Postprocedural TIMI flow 0-1 (%) 2 (%) 3 (%)

1.13.3

95.6

06.7

93.31.0

1.15.6

93.31.0

RD (mm) 3.13 + 0.51 3.2 + 0.44 0.66 3.14 + 0.48 1.0

% stenosis pre 89.1 + 9.51 88.1 + 9.3 1.0 88.3 + 9.9 1.0

% stenosis post 6.9 + 5.6 6.6 + 6.1 1.0 7.1 + 6.1 1.0

Stent diameter (mm) 3.12 + 0.46 3.17 + 0.38 0.9 3.08 + 0.32 0.96

Max Stent diameter (mm) 3.26 + 0.47 3.27 + 0.4 1.0 3.25 + 0.43 1.0

Total Stent length (mm) 20.25 + 5.6 21.8 + 7.1 0.2 22.2 + 7.8 0.11

N. stents 1.11 + 0.35 1.28 + 0.56 0.036 1.19 + 0.47 0.42

Direct stenting (%) 26.7 24.4 1.0 28.9 1.0

Procedural Success (%) 95.6 93.3 1.0 93.3 1.0

Gp IIb-IIIa inhibitors (%) 100 100 1.0 100 1.0

Angiographic and procedural characteristics of the three groups of patients


0

10

20

30

TLR Death reMI MACEs IST

0

10

20

30


01020304050


BMS

PES

SES

* #

* #

* #

* #

* #

* #

40

%

%

%

*p<0.05 vs BMS # p<0.05 vs BMS

1 yearoutcome

3 yearoutcome

3 to 6 yearoutcome


Death, (%) 13.3 8.9 7.8 0.66 0.36 0.56 0.23

reMI, (%) 14.4 8.9 10 0.59 0.25 0.66 0.34

reMI and/or death, (%) 23.3 17.8 16.7 0.74 0.36 0.68 0.26

TLR, (%) 22.2 6.7 5.6 0.27 0.005 0.22 0.003

TLR and/or death, (%) 31.1 15.6 13.3 0.46 0.017 0.38 0.005

TVR, (%) 23.3 7.8 6.7 0.30 0.006 0.25 0.003

TVR and/or death, (%) 32.2 16.7 14.4 0.47 0.018 0.40 0.005

IST, (%) 8.9 5.6 4.4 0.64 0.44 0.48 0.23

Definite, (%) 1.1 1.1 1.1

Probable, (%) 2.2 1.1 1.1

Possible, (%) 5.6 3.3 2.2

IST and/or death, (%) 14.4 10 10 0.71 0.42 0.66 0.34

MACEs, (%) 40.0 23.3 22.2 0.52 0.016 0.48 0.009

BMSN=90

PESN=90

SESN=90 HR P HR P

PES vs BMS SES vs BMS

3 to 6 years Clinical Outcomes (median 4.3 years)


The main finding of the present study is that PES and SES are more effective than BMS mainly because of a reduction in TLR, with no excess risk of thrombotic complications.

Our study demonstrates the long-term safety and benefits of both SES and PES compared with BMS.

Of relevance, unlike the vast majority of randomized trials conducted to date, the superiority of SES and PES was observed without the use of routine angiographic follow-up in our trial.

CONCLUSIONS


MAJOR LIMITATIONS OF STUDY

Because of a relatively late randomization strategy (after initial angiography), patients have for the most part been selected;

Despite long-term follow-up data, as a result of the relatively small sample size, this trial cannot provide definite conclusions on DES safety in terms of death and reinfarction, which we hope will be provided by large randomized trials.

e. di lorenzo a.o.r.n. “s. g. moscati” – avellino - italy long-term outcome of drug-eluting...

Documents