Patras University Hospital GREEK ANTIPLATET REGISTRY 2012 Dimitrios Alexopoulos, MD, FACC, FESC Cardiology Department, Patras University Hospital, Patras, Rio, Greece.
Patras University Hospital I, Dimitrios Alexopoulos, have received honoraria for lecturing and research grants from: Astra Zeneca
Patras University Hospital PCI-CURE
Clinical outcome studies Prasugrel vs Clopidogrel Ticagrelor vs Clopidogrel Increased bleeding
Patras University Hospital
Wallentin L, et al. N Engl J Med. 2009;361:1045. Patras University Hospital
Patras University Hospital
Patras University Hospital
Prevalence of contraindications and conditions for precaution for prasugrel administration in a real world acute coronary syndrome population. Alexopoulos et al, J Thromb Thrombolysis 2011
Patras University Hospital GREEK ANTIPLATELET REGISTRY supported by HCS
REGISTRY 8 GREEK HOSPITALS UH PATRAS (Davlouros P, Xanthopoulou I, Mavronasiou E, Stavrou K, Tsoni E, Siapika A, Theodorou P, Christopoulou G, Gizas V, Alexopoulos D. ) UH IRAKLIO (Hamilos M, Petousis S, Vardas P) UH ALEXANDROUPOLI (Stakos D) UH LARISSA (Sitafidis G, Karayannis G, Triposkiadis F) UH IOANNINA (Ntallas I, Goudevenos I) GENIMMATAS (Deftereos S, Aggelidis, Giannopoulos G, Pyrgakis V) ALEXANDRA (Loizos S, Kanakakis I) IPPOKRATEIO (Vavouranakis M) START1/2012 TARGET 1000 PATIENTS F-UP 1YEAR
Patras University Hospital QUESTIONS What antiplatelet is selected in real life in 2012? What is the prevalence of contraindications/special conditions for antiplatelet treatment? Is the prescribed treatment on-label or how often the guidelines are followed?
Patras University Hospital QUESTIONS Are the new agents prescribed off-label? Is clopidogrel prescribed off-label? What about switching therapies in-hospital or out of hospital? Are the new agents used post thrombolysis? What is the discontinuation rate and why?
TOTAL N=875 Men 720 (82.3%) Age 62.5±18.8 PCI Hospital -UH PATRAS 417(47.7) -GENIMMATAS 134(15.3) -UH IOANNINA 147(16.8) -UH IRAKLIO 25(2.9) -UH ALEXANDROUPOLI 1(0.1) -UH LARISSA 132(15.1) -IPPOKRATEIO 2(0.2) -ALEXANDRA 17(1.9) TRANSFER FROM OTHER HOSPITAL TO PCI HOSPITAL 547(62.5)
RISK FACTORS Dyslipidemia 400(45.7) Hypertension 490(56.0) Diabetes 204(23.3) -on insulin 35(4.0) Smoking 470(53.7) Family Hx of CAD 242(27.7) Prior MI 108(12.3) Prior PCI 102(11.7) Prior CABG 21(2.4)
Treatment at home Αspirin 180(20.6) Clopidogrel 111(12.7) Prasugrel 3(0.3) Ticagrelor 2(0.2) Acenocoumarol 21(2.4) Β-blockers 180(20.6) Νitrates 54(6.2) Statin 228(26.1) Calcium blockers 149 (17.0) PPI 109(12.5) ΑCΕ/ATII inhibitors 248(28.3)
Acute coronary syndrome -STEMI 441(50.4) -Non STEMI 223(25.5) -Unstable angina 211(24.1) Hemodynamic instability on admission 36(4.1) Treatment of STEMI -Primary PCI 253(57.4) -Thrombolysis 113(25.6) -Rescue PCI 28(6.3) -No reperfusion attempt in the first 24 hrs 47(10.7)
1. P2Y12 inhibitors contraindications Clopidogrel Prasugrel Ticagrelor Known allergy 1(0.1) 0(0) 1(0.1) Active bleeding 4(0.5) 4(0.5) 4(0.5) Prior stroke/tia NA 35(4.0) ΝΑ Hx intracranial bleeding Moderate/severe liver insufficiency ΝΑ 5(0.6) 5(0.6) NA NA 1(0.5)
Special condition Clopidogrel Prasugrel Τicagrelor Age 75 ΝΑ 163(18.6) N A Weight< 60Kg NA 27(3.1) N A Moderate liver insufficiency 1(0.1) 1(0.1) ΝΑ Lactose intolerance ΝΑ 1(0.1) ΝΑ Recent trauma/surgery 4(0.5) 4(0.5) 4(0.5) Recent GI bleeding 8(0.9) 8(0.9) 8(0.9) Concomitant treatment at home that increases bleeding risk 30(3.4) 30(3.4) 30(3.4)
Clopidogrel Prasugrel Σicagrelor Thrombolysis NA 141(16.1) 141(16.1) Chronic Kidney Disease 27(3.1) 27(3.1) 27(3.1) Concomitant diseases that 49(5.6) 49(5.6) 49(5.6) increases the bleeding risk Malignancy 21(2.4) 21(2.4) 21(2.4) Hx ulcer/gastritis /ischemic 28(3.2) 28(3.2) 28(3.2) colitis/inflammatory bowel disease Uret. Cyst thelomas 3(0.3) 3(0.3) 3(0.3) Recent CVA 2(0.2) ΝΑ 2(0.2)
Clopidogrel Prasugrel Σicagrelor Concomitant use of moderate/strong CYP2C19 inhibitors(i.e. omeprazol) 53(6.1) ΝΑ ΝΑ Concomitant use of strong CYP3A4 inductors NA NA 4(0.5) Severe COPD ΝΑ ΝΑ 37(4.2) Increased risk for bradycardia ΝΑ ΝΑ 6(0.7) Hyperuricaemia/uric arthritis paroxysms ΝΑ ΝΑ 55(6.3)
Patras University Hospital At least one absolute contraindication or special condition requiring precaution for administering clopidogrel 16.7% prasugrel 42.7% ticagrelor 35.5%
Prevalence of at least one contraindication/ special condition/overlapping Patras University Hospital
Patras University Hospital TREATMENT AT DISCHARGE FROM PCI HOSPITAL Clopidogrel N=313 (36.5%) Prasugrel N=225(26.3%) Τicagrelor Ν=318(37.1%)
Patras University Hospital At least one contraindication/special condition for clopidogrel/ prasugrel/ticagrelor simultaneously Ν=117 (13.3%) NO LABEL CATEGORY??? Treatment at discharge Clopidogrel 70 (59.8%) Prasugrel 16 (13.7%) ΤIcagrelor 31 (26.5%)
2. In hospital bleeding events in patients on constant treatment No bleeding Ν=492 BARC 1 Ν=23 BARC 2 Ν=13 BARC 3 Ν=12 Men 405(82.3) 20(87.0) 10(76.9) 7(58.3) 0.2 Age 63.4±18.4 65.9±13.3 65.5(14.6) 69.2±11.9 0.6 ΒΜΙ 28.2±4.1 28.5±4.9 28.8±4.9 26.4±4.4 0.5 Hypertension 268(54.5) 19(82.6) 10(76.9) 6(50.0) 0.02 Smoking 254(51.6) 9(39.1) 7(53.8) 7(58.3) 0.5 Diabetes Mellitus 110(22.4) 8(34.8) 4(30.8) 3(25.0) 0.4 CKD 12(2.4) 1(4.3) 0(0) 2(16.7) 0.06 Concomitant diseases 26(5.3) 2(8.7) 0(0) 2(16.7) 0.2 increasing bleeding risk Treatment at home that increases bleeding risk 19(3.9) 2(8.7) 1(7.7) 0(0) 0.3 P
No bleeding BARC1 BARC2 BARC3 p STEMI 263(53.5) 7(30.4) 8(61.5) 7(58.3) 0.2 Primary PCI 168(34.1) 6(26.1) 7(53.8) 4(33.3) 0.2 Thrombolysis 62(12.6) 0(0) 1(7.7) 2(16.7) 0.5 Rescue PCI 11(7.6) 0(0) 0(0) 0(0) 1.0 Treatment at PCI hospital ΙΙβ/ΙΙΙα inhibitors 49(10.0) 4(17.4) 2(15.4) 2(16.7) 0.3 Bivalirudin 116(23.6) 6(26.1) 4(30.8) 2(16.7) 0.9 Fondaparinux 57(11.6) 1(4.3) 1(7.7) 1(8.3) 0.9 LMWH 24(4.9) 0(0) 0(0) 1(8.3) 0.5 Clopidogrel 278(56.6) 8(34.8) 6(46.2) 8(66.7) 0.1 Prasugrel 68(14.2) 6(27.3) 2(15.4) 0(0) 0.2 Τicagrelor 146(30.4) 9(40.9) 5(38.5) 4(33.3) 0.6
Risk factors for in-hospital bleeding events
3. Antithrombotic treatments- Differences between hospitals UH Patras N=417 Genimmatas N=134 UH ioannina N=147 UH Larissa N=132 P Treatment before admission Αspirin 76(18.2) 34(25.4) 25(17.0) 40(30.3) 0.01 Clopidogrel 45(10.8) 19(14.2) 18(12.2) 26(19.7) 0.08 Prasugrel 1(0.2) 1(0.7) 0(0) 1(0.8) 0.3 Τicagrelor 0(0) 1(0.7) 0(0) 1(0.8) 0.1 Acenocoumarol 9(2.2) 5(3.7) 5(3.4) 2(1.5) 0.6
Admission for UH Patras N=417 Genimmatas N=134 UH Ioannina N=147 UH Larissa N=132 P STEMI 208(49.9) 73(54.5) 75(51.0) 59(44.7) 0.5 Non STEMI 119(28.5) 40(29.9) 30(20.4) 23(17.4) 0.02 Unstable angina 90(21.6) 21(15.7) 42(28.6) 50(37.9) <0.001 Treatment of STEMI -Primary PCI 156(75.0) 57(78.1) 18(24.0) 2(3.4) <0.001 -Thrombolysis 23(11.1) 8(11.0) 43(57.3) 36(61.0) <0.001 -Rescue PCI 10(4.8) 5(6.8) 8(10.7) 4(6.8) 0.3 -No reperfusion 19(9.1) 3(4.1) 6(8.0) 17(28.8) <0.001 attempt in the first 24 hrs Transfer from another hospital to the PCI center 299(71.7) 62(46.3) 99(67.3) 61(46.2) <0.001
UH Patras N=417 Genimmatas N=134 UH Ioannina N=147 UH Larissa N=132 P Treatment at PCI Hospital IIB/IIIa inhibitors 20(4.8) 26(19.4) 25(17.0) 14(10.6) <0.001 Bivalirudin 143(34.3) 28(20.9) 0(0) 28(21.2) <0.001 Fondaparinux 14(3.4) 21(15.7) 5(3.4) 72(54.5) <0.001 LMWH 10(2.4) 1(0.7) 7(4.8) 7(5.3) 0.07 Treatment at discharge from the PCI hospital N=811 N=411 N=129 N=140 N=131 Αspirin 406(98.8) 128(99.2) 140(100) 131(100) 0.4 Triflusal 5(1.2) 1(0.8) 0(0) 0(0) 0.4 Clopidogrel 91(22.1) 53(41.1) 97(69.3) 50(38.2) <0.001 Prasugrel 154(37.5) 17(13.2) 12(8.6) 37(28.2) <0.001 Τicagrelor 166(40.4) 59(45.7) 31(22.1) 44(33.6) <0.001 Αcenocoumarol 19(4.6) 2(1.6) 7(5.0) 4(3.1) 0.4
Patras University Hospital 4. In-hospital switching of P2Y12 inhibitors treatment How often? Change to a stronger agent (upgrade) or to weaker (downgrade)? Is it on label? Clopidogrel to Τicagrelor (suggested by the ESC quidelines) Is it safe?
Patras University Hospital Results Jan- Αug 2012 875 patients with adequate data from 8 Greek hospitals In 540 (61.7%) no change of P2Y12 inhibitors during hospitalization In 333 (38.1%) switching 2 (0.2%) patients died before receiving antiplatelet treatment-excluded
Clinical characteristics Total Ν=873 No switch Ν=540 Switch Ν=333 Men 719(82.4) 442(81.9) 277(83.2) 0.6 Age 62.3±18.9 63.1±12.6 59.7±11.3 <0.001 ΒΜΙ (Kg/m 2 ) 28.2±4.2 28.2±4.2 28.3±4.4 0.7 Hypertension 488(55.9) 303(56.1) 185(55.6) 0.9 Smoking 469(53.7) 277(51.3) 192(57.7) 0.07 Diabetes 202(23.1) 125(23.1) 77(23.1) 1.0 On insulin 34(3.9) 21(3.9) 13(3.9) 1.0 Dyslipidaemia 400(45.8) 243(45.0) 157(47.1) 0.6 P
Total No switch Switch Ν=873 Ν=540 Ν=333 CKD 26(3.0) 15(2.8) 11(3.3) 0.7 Prior MI 108(12.4) 62(11.5) 46(13.8) 0.3 Prior PCI 102(11.7) 59(10.9) 43(12.9) 0.4 Treatment at home -Clopidogrel 111(12.7) 58(10.7) 53(15.9) 0.03 -Prasugrel 3(0.3) 2(0.4) 1(0.3) 1.0 -Τicagrelor 2(0.2) 2(0.4) 0(0) 0.5 -Αcenocoumarol 20(2.3) 17(3.1) 3(0.9) 0.04
Admission for Total Ν=873 No switch Ν=540 Switch Ν=333 P -STEMI 439(50.3) 285(52.8) 154(46.2) 0.07 -Non STEMI 223(25.5) 123(22.8) 100(30.0) 0.02 -Unstable angina 211(24.2) 132(24.4) 79(23.7) 0.9 Hemodynamic 35(4.0) 27(5.0) 8(2.4) 0.07 instability Transfer from another center 547(62.7) 311(57.6) 236(70.9) <0.001
Total Ν=873 No switch Ν=540 Switch Ν=333 P Primary PCI 251(57.2) 185(64.9) 66(42.9) <0.001 Thrombolysis 113(25.7) 65(22.8) 48(31.2) 0.07 Rescue PCI 28(6.4) 11(3.9) 17(11.0) 0.007 No reperfusion 47(10.7) 24(8.4) 23(14.9) 0.05 attempt in the first 24 hrs Treatment at PCI hospital IIΒ/III Inhibitors 94(10.8) 57(10.6) 37(11.1) 0.8 Bivalirudin 202(23.1) 128(23.7) 74(22.2) 0.7
Patras University Hospital In 21(6.3%) cases there was switch from strong agent to clopidogrel (downgrade) 5 received clopidogrel during triple antithrombotic treatment 4 had bleeding event in-hospital
In-hospital events Total Ν=873 No switch Ν=540 Switch Ν=333 P MACEs (death, MI, urgent revasc, CVA) 23(2.6) 17(3.1) 6(1.8) 0.3 Bleeding 86(9.9) 48(8.9) 38(11.4) 0.2 -BARC 1 41(4.7) 23(4.3) 18(5.4) 0.5 -BARC 2 26(3.0) 13(2.4) 13(3.9) 0.2 -BARC 3 19(2.2) 12(2.2) 7(2.1) 1.0
5. Follow-up 30 days MACEs (death, MI, urgent revasc, CVS) Total Ν=558 21(3.8) Bleeding 107(19.2) -BARC 1 98(17.6) -BARC 2 5(0.9) -BARC 3 4(0.7)
Risk factors for bleeding events during 30 days Patras University Hospital Multivariate analysis (logistic regression-enter method)
Patras University Hospital GREEK ANTIPLATELET REGISTRY supported by HCS It is a reality!
REGISTRY 8 GREEK HOSPITALS ΠΠΓΝ ΠΑΣΡΩΝ (Νηαβινύξνο Π, Ξαλζνπνύινπ Ι, Μαπξνλάζηνπ Δ, ηαύξνπ Κ, Σζώλε Δ, ηάπηθα Α, Θενδώξνπ Π, Υξηζηνπνύινπ Γ, Γθίδαο Β, Αιεμόπνπινο Γ) ΠΔΠΑΓΝ ΗΡΑΚΛΔΙΟΤ (Υακειόο Μ, Πεηνύζεο, Βάξδαο Π) ΠΠΓΝ ΑΛΔΞΑΝΓΡΟΤΠΟΛΗ (ηάθνο Γ) ΠΠΓΝ ΛΑΡΙΑ (ηηαθίδεο Γ, Καξαγηάλλεο Γ, Παξίζεο Υ, Σξππνζθηάδεο Φ) ΠΠΓΝ ΙΩΑΝΝΙΝΩΝ (Νηάιιαο Ι, Γνπδέβελνο Ι) ΓΝ ΚΡΑΣΙΚΟ ΑΘΗΝΩΝ (Γεπηεξαίνο, Αγγειίδεο -, Γηαλλόπνπινο Γ, Ππξγάθεο Β) ΑΛΔΞΑΝΓΡΑ (Λνίδνο, Καλαθάθεο Ι) ΙΠΠΟΚΡΑΣΔΙΟ (Βαβνπξαλάθεο Μ) ΣΟΥΟ 1000 ΑΘ F-UP 1 ΔΣΟ
Patras University Hospital 5. Follow-up 30 ημερών MACEs (θϊνατοσ, ϋμφραγμα, επεύγουςα επαναγγεύωςη, αγγειακό εγκεφαλικό) Αιμορραγύα οποιαςδόποτε Σύνολο ασθενών Χωρίς αλλαγή του P2Y12 αναστολέα Αλλαγή του P2Y12 αναστολέα Ν=558 Ν=332 Ν=226 21(3.8) 13(3.9) 8(3.5) 1.0 107(19.2) 51(15.4) 56(24.8) 0.006 βαρύτητασ -BARC 1 98(17.6) 47(14.2) 51(22.6) 0.01 -BARC 2 5(0.9) 2(0.6) 3(1.3) 0.4 -BARC 3 4(0.7) 2(0.6) 2(0.9) 1.0 P
Patras University Hospital
Patras University Hospital Συμπεράςματα switching Η ενδονοςοκομειακό αλλαγό του P2Y12 αναςτολϋα εύναι ςυχνό και ςτην πλειοψηφύα των περιπτώςεων αφορϊ ςε μετϊβαςη από κλοπιδογρϋλη ςε νεότερο παρϊγοντα Το όμιςυ των περιπτώςεων μετϊβαςησ ςε νεότερο παρϊγοντα αυτόσ όταν τικαγκρελόρη Η ενδονοςοκομειακό αλλαγό του P2Y12 αναςτολϋα δεν ςυνδϋεται με αυξημϋνο κύνδυνο για αιμορραγικό ςύμβαμα οποιαςδόποτε βαρύτητασ ςτισ 30 ημϋρεσ