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<0.5% <1% NSTEMI8% %2-3% STEMI9-11%2-4%2-5% BCIS CCAD database 2009

MACE and bleeding in current practice BCIS CCAD database 2009

Bleeding predictors Mehta et al Circ Cardiov Int 2009;2:222

Bleeding predictors Mehta et al Circ Cardiov Int 2009;2:222

Summary Bleeding is common and it does matter 50% of bleeding is access site related Consider MACE and bleeding risks - Clinical syndrome - Patient specific factors - Access site - Pharmacology Individualize therapy to balance: thrombotic vs. bleeding events