MICHELANGELO: OASIS 5 Women s Substudy

Transcription

1 MICHELANGELO: OASIS 5 Wome s Substudy Dr. Eva Swah Departmet of Cardiology, Heart Cetre, Uiversity Hospital, Liköpig Swede Disclosure Fuded by Saofi-Sythelabo, Orgao NV ad GSK Dr. Swah has o coflicts of iterest

2 Backgroud Wome with NSTE ACS have less severe CAD ad better progosis tha me. Some treatmets (eg LMWH or CABG surgery) are associated with a higher risk i wome. Others (GPIIB/ IIIa ihib) appear ieffective. Radomized trials of routie ivasive strategy i NSTE ACS show beefits i me but the results i wome are cotradictory.

3 Death/MI FRISCII (2001) (12 m f-u) RITA3 (2002) (12 m f-u) TACTICS (2002) (6 m f-u) Routie ivasive 43 (12.4) 30 (8.6) 26 (6.6) Selective ivasive 34 (8.5) 17 (5.1) 35 (9.7)

4 MICHELANGELO: OASIS 5 Wome s Substudy Female Patiets Radomized to OASIS 5 (NSTE ACS) Fodpariux vs Eoxapari Radomized to WSS Routie Ivasive Selective Ivasive Cath followed by PCI/CABG withi 7 days Primary Outcomes over duratio of 2 yr follow-up 1. Death/MI/Stroke/Refractory ischemia 2. Death/MI/Stroke 184 patiets radomized Oly i presece of symptoms or severe ischemia

5 Study Desig A radomized, iteratioal, multi-ceter ope trial Sub-study of MICHELANGELO: OASIS-5 trial. Eligible female patiets i participatig OASIS 5 ceters were radomized to receive either: routie early coroary agiography ad, if appropriate, itervetio withi 7 days of radomizatio or selective ivasive strategy (coroary agiography oly i case of symptoms i.e. severe ischemia durig idex hospital admissio or o a stress test).

6 Study Objectives To evaluate whether, amog wome with NSTACS, a early ivasive strategy, is superior to a selective ivasive strategy i terms of Death/MI/Stroke over a duratio of 2 year follow-up All patiets were cocurretly maaged with itese ati-ischemic ad atithrombotic medicatio durig idex hospitalizatio.

7 Idicatios for revascularizatio i the selective ivasive group Refractory ischemia. New ST elevatio. Developmet of hemodyamic istability or CHF. Itractable life-threateig arrhythmia. Icapacitatig agia or severe ischemia at a stress test. Icapacitatig agia despite optimal medical therapy durig follow-up. Reifarctio durig follow-up.

8 Follow-up Schedule As per the mai study at 30, 90 ad 180 days Out-patiet visit or telephoe cotact with survivors at 1 ad 2 years. Appropriate CRF ad evet forms filled i accordig to the protocol.

9 Statistical Cosideratios Based o the over all results of the FRISC II trial we assumed a reductio i the rate of death, MI from 17.5 to 12.5 at 3 years with a routie ivasive strategy. To detect a relative risk reductio of 28.5, with 80 power, a sample size of 1,600 was plaed. The curtailmet i the sample size as well as follow-up time reduced the effective power to about 12 to detect the hypothesized reductio i outcome(2 sided α=0.05). The effect of Ivasive strategy o outcomes was assessed usig Cox s Proportioal Hazard Model.

10 Baselie Characteristics Age (SD) Previous MI Previous PCI CABG Surgery Stroke PAD Hypertesio Diabetes Curret Smoker Oset to Rad (hrs) Selective Ivasive ( = 92) (8.8) /- 6.3 Routie Ivasive ( = 92) (9.2) /- 6.6

11 Ischemic Symptoms/ECG/ Ezymes, Biomarkers Selective Ivasive ( = 92) Routie Ivasive ( = 92) Tropoi or CK-MB > ULN ECG compatible with ischemia ST depressio 0.5 mm Ay ECG abormality

12 Cocomitat Medicatios durig Iitial Hospitalizatio Selective Ivasive ( = 92) Routie Ivasive ( = 92) ASA Clopidogrel/Ticlopidie Dual Ati-platelet Rx GP IIb/IIIa IV UFH LMWH Oly LMWH Beta Blocker ACE/ARB Statis

13 Itervetios durig Iitial Hospitalizatio Selective Ivasive ( = 92) Routie Ivasive ( = 92) Coroary Agiography PCI CABG Surgery

14 Itervetios durig Log term Follow-up Selective Ivasive ( = 92) Routie Ivasive ( = 92) Coroary Agiography PCI CABG Surgery

15 Cox PH Ratios: 2 yr outcome Selective Ivasive ( = 92) Routie Ivasive ( = 92) Hazard Ratio (95 CI) Death/MI/Stroke ( ) Death/MI/RI ( ) Death/MI ( ) Death ( ) MI ( ) Stroke ( ) Major Bleedig ( ) Death/MI/Stroke/ Major Bldg ( )

16 Death/MI/Stroke Cumulative Hazard Routie ivasive Selective ivasive Days

17 Death Routie ivasive Selective ivasive Days Cumulative Hazard

18 MICHELANGELO: OASIS 5 Wome s Substudy Female Patiets Radomized to OASIS 5 (NSTE ACS) Fodpariux vs Eoxapari Radomized to WSS Routie Ivasive Selective Ivasive Cath followed by PCI/CABG withi 7 days Primary Outcomes over duratio of 2 yr follow-up 1. Death/MI/Stroke/Refractory ischemia 2. Death/MI/Stroke 184 patiets radomized Oly i presece of symptoms or severe ischemia

19 Meta aalysis - Death/MI Study ame Death or MI / Total Statistics for each study Odds ratio ad 95 CI Routie Selective Odds Lower Upper Ivasive Ivasive ratio limit limit p-value FRISC II 43 / / RITA 3 30 / / TACTICS 26 / / OASIS 5 13 / / / / Favours Early Ivasive Favours Selective Ivasive

20 Meta aalysis - Death Study ame Dead / Total Statistics for each study Odds ratio ad 95 CI Routie Selective Odds Lower Upper Ivasive Ivasive ratio limit limit p-value FRISC II 14 / / RITA 3 18 / / TACTICS 15 / / OASIS 5 8 / 92 1 / / / Favours Early Ivasive Favours Selective Ivasive

21 FINAL Erollmet by Coutry Coutry No. of Sites No. of Patiets Argetia Swede Polad South Africa TOTAL

22 Coclusios I this study, wome with NSTE ACS did ot beefit from a routie ivasive strategy. O the cotrary, patiets radomised to a routie ivasive strategy had a higher mortality rate. The results take together with the results of previous larger trials suggest that the results from me do ot ecessarily apply to wome ad that large scale radomised trials i wome are eeded to determie the optimal strategy i NSTE ACS.