1. PRAGUE-8 Study Clopidogrel > 6 hours before elective CAG vs. a few minutes before PCI in stable angina ? P Widimský, Z Moťovská, S Šimek, P Kala & PRAGUE-8 trial Investigators Charles University Prague (Third Medical Faculty, First Medical Faculty, Medical Faculty Hradec Kralové), University Hospital Brno and Regional Hospital Liberec. Open, randomized multicenter trial. Support: Research project MSM0021620817 Charles University Prague. Nothing else to disclose, no support from industry.

2. The full list of investigators. Charles University Prague - 3rd Medical Faculty and University Hospital Kralovske Vinohrady (442 pts. enrolled): Zuzana MOTOVSKA, Petr Widimský, Robert Petr, Dana Bílková, Václav Bufka, Pavel Gregor, Radovan Jirmář, Petr Ošťádal, Tomáš Buděšínský, Jaroslav Dvořák, Viktor Kočka, Libor Lisa. Charles University Prague – 1st Medical Faculty and General University Hospital (334 pts. enrolled): Stanislav Šimek, Hana Skalická, Jan Horák, Petr Kuchynka, Aleš Linhart, Michael Aschermann. Masaryk University & University Hospital Brno (204 pts. enrolled): Petr Kala, Martin Poloczek, Roman Miklík, Jindřich Špinar, Lenka Kubková, Jan Maňoušek. Charles University Prague – Medical Faculty & University Hospital Hradec Kralove (24 pts. enrolled): Lucie Horáková, Radek Pudil, Jan Vojáček, Josef Šťásek, Josef Bis, Jaroslav Dušek, Pavel Polanský, Miroslav Brtko. Regional Hospital Liberec (24 pts. enrolled): František Holm, Zdeněk Šembera, Jiri Maly.

3. Background. Clopidogrel pre-treatment before planned elective PCI reduces periprocedural complications. Current practice: very few „planned“ PCI’s (i.e. separate procedures from CAG), but rather „ad-hoc“ PCI’s (unplanned, indicated and performed immediately after planned elective CAG). ESC guidelines for PCI: Evidence is lacking. Expert consesnsus: clopidogrel pre-treatment to all elective CAG’s (to achieve therapeutic levels at the time of possible ad-hoc PCI). Is this valid ??

4. Inclusion criteriaExclusion criteria Planned elective CAG for suspected or proven coronary artery disease Thienopyridine treatment in previous two weeks Signed written informed consent Contraindication for clopidogrel Age ≥ 18 years Clinically significant bleeding in last 3 months CAG scheduled less than 6 hours after potential randomization

5. Randomization on the day before CAG Group A „nonselective“ clopidogrel use (n = 513) clopidogrel 600 mg > 6 hours before each CAG (mean time interval between clopidogrel loading dose and CAG was 20,6 hours) Group B „selective“ clopidogrel use (n = 515) clopidogrel 600 mg in the cath-lab after CAG, only to patients, undergoing subsequent PCI

6. Patients baseline characteristics N = 1028 Group A (non-selective clopidogrel before CAG) Group B (selective clopidogrel before PCI) P val ue N =513515 Age6566n.s. Females36%39%n.s. Stabilized ACS13%15%n.s. Proven or suspected chronic stable CAD 87%85%n.s. Previous MI27%28%n.s. Diabetes mellitus28% n.s. Mean INR at randomization1,061,05n.s. Mean APTT at randomization35 s34 sn.s. Mean creatinine94 (22 pts. > 140) 94 (24 pts. > 140) n.s. Mean ejection fraction (echo) 57%58%n.s.

7. Primary end-point (death / periprocedural MI / stroke or TIA / re-intervention within 7 days, %) n.s.

8. Periprocedural troponin elevation (% of pts. with >3x ULN after intervention) n.s.

9. Bleeding complications (clinically significant, major & minor, %) p = 0,006 p = 0,02 Definitions: Major: intracranial or clinically overt bleeding with a decrease in hemoglobin > 50 g/l Minor: clinically visible with a decrease in hemoglobin ≤ 50 g/l according to the TIMI criteria

10. Individual end-points [n] Events [n]Group A (non-selective clopidogrel before CAG) Group B (selective clopidogrel before PCI) P valu e Death of any cause10 n.s. Periprocedural MI (CK-MB >3x ULN) 00 n.s. Periprocedural stroke / TIA 12 n.s. Reintervention22 n.s. Primary end-point44 n.s. Impairment of TIMI- flow to <3 after PCI 60 n.s.

11. Clopidogrel and early CABG (n = 28) Only 2,7% of all CAG patients underwent early (within <7 days) CABG.

12. Conclusion. Routine clopidogrel pretreatment before elective CAG in stable coronary artery disease is not justified. It increased the risk of bleeding complications, while the benefit on ischemic periprocedural complications was not significant. Clopidogrel should be given only to patients with known CAG who undergo PCI and this can be done safely in the catheterization laboratory between the two procedures.