Nick Alp Milton Keynes Hospital NHS FT Oxford Radcliffe NHS Trust Bleeding risks in the major trials – It does matter.

Nick Alp Milton Keynes Hospital NHS FT Oxford Radcliffe NHS Trust Bleeding risks in the major trials It does matter Likelihood of bleeding Severity and consequences of bleeding Direct Indirect Death (3-fold increased death risk with major bleed) MI Stroke Prolonged hospitalization Why does bleeding matter? Moscucci et al (GRACE) EHJ 2003;24:1815 Thrombosis/bleeding balance Thrombotic events (MACE) Bleeding events Intensity of antiplatelet + antithrombotic therapy Net adverse clinical events TIMI MajorIntracranial >5g/dl Hb drop MinorHaematemesis Haematuria 3-5g/dl Hb drop InsignificantOther bleeding Bleeding definitions GUSTO SevereDeadly; Intracranial BP Compromise ModerateTransfusion needed InsignificantOther bleeding National PCI registries vs Almost all patients included Outcomes not adjudicated Non-uniform bleeding definitions Under-reporting of bleeds likely How common is bleeding? Randomized trials Marked patient selection bias Outcomes adjudicated Agreed bleeding definitions Some important bleeds excluded Most bleeding events reported Bleeding in the real world (USA) US National Cardiovascular Data Registry PCI centres 302,152 procedures Bleeding definitions (CathPCI database): - Transfusion - >3g/dl Hb drop - Prolonged hospital stay Mehta et al Circ Cardiov Int 2009;2:222 Incidence of bleeding TIMI major + minor = 2.4% Hospital range 0.5%-5.5% NB no adjudication, under-reporting bias likely Mehta et al Circ Cardiov Int 2009;2:222 Site of bleeding Access site Gastrointestinal Retroperitoneal Genitourinary Other/unknown 38% 19% 13% 20% >1 site N=302,152 Mehta et al Circ Cardiov Int 2009;2:222 Bleeding in the major trials StrategyStudyMACE (%) Major bleed Minor bleed Clopidogrel vs ASAPCI-CURE (30 d) 4.5 vs vs vs 2.1 Prasugrel vs ClopidogrelTRITON-TIMI38 (All) 12.3 vs vs vs 2.0 Abciximab vs placebo (+ ASA + clopidogrel) ISAR-REACT vs vs vs 3.3 Bivalirudin vs heparin +/- GPI REPLACE vs vs vs 3.0 Fondaparinax vs Enoxaparin OASIS vs vs vs 5.5 Prasugrel vs ClopidogrelTRITON-TIMI38 (STEMI) 9.7 vs vs vs 2.0 Facilitated PCI abciximab +/- TPA + PCI FINESSE 9.8 vs 10.5 vs vs 4.1 vs vs 6.0 vs 9.7 Bivalirudin vs heparin + GPI HORIZONS-AMI (1 yr) 11.9 vs vs vs 4.8 MACE and bleeding in current practice SyndromeMACEMajor bleedMinor bleed Stable CAD