B alloon-pump assisted C oronary I ntervention S tudy BCIS-1 Simon Redwood St Thomas’ Hospital / King’s College London On behalf of the BCIS-1 Investigators Steering Committee: Divaka Perera, Rod Stables, Jean Booth, Martyn Thomas

1 Potential conflicts of interest Potential conflicts of interest Speaker’s name: Simon Redwood √ I do not have any potential conflict of interest This trial was supported by unrestricted grants from: Datascope/ Maquet Eli Lilly Cordis

Trial Organization Steering Committee Divaka Perera, Rod Stables, Martyn Thomas, Jean Booth, Simon Redwood Clinical Events Committee James Cotton, Nick Curzen, Adam de Belder, David Roberts Data Monitoring and Safety Committee Peter Ludman (Chair), Gerald Stansby, Chris Palmer Clinical Trials and Evaluation Unit Jean Booth, Fiona Nugara, Marcus Flather, Charlotte Gillam, Michael Roughton, Winston Banya

Elective vs provisional IABP in high-risk PCI 133 pts EF <30, elective PCI Elective IABP, 61 pts. Jeopardy Score Provisional IABP, 72 pts. Jeopardy Score (p=0.008) Correlates of MACE Odds Ratio Elective IABP0.11 Jeopardy Score5.37 % Briguori et al, AHJ 2003;145:700-7 P = 0.01 P = 0.29

Objectives: To compare the efficacy and safety of elective Intra-Aortic Balloon Pump (IABP) insertion prior to high-risk PCI vs. conventional treatment (with no planned IABP use) Structure: Prospective, open, randomized trial Prospective, open, randomized trial 17 UK centres 17 UK centres n=300 (150 in each arm) n=300 (150 in each arm) Sample Size = 274 pts (predicted MACCE 5% vs. 15%, β=80%, α= 5%) B alloon-pump assisted C oronary I ntervention S tudy

LVEF < 30% Jeopardy Score ≥ 8 Randomize 6 month follow-up Elective IABP Insertion No Planned IABP PCI Remove IABP 4-24 hrs after PCI Hospital Follow-up To discharge or 28 days

Primary Outcome Measure Major Adverse Cardiovascular or Cerebral Events (MACCE) at hospital discharge or 28 days (whichever is sooner), including All-Cause Death All-Cause Death Acute MI Acute MI Further revascularization by PCI or CABG Further revascularization by PCI or CABG CVA CVA BCIS-1 Perera et al AHJ 2009; in press

Secondary Outcome Measures Six month mortality Six month mortality Procedural complications Procedural complications Prolonged hypotension ORProlonged hypotension OR VT/VF requiring cardioversion ORVT/VF requiring cardioversion OR Cardiac arrest requiring CPR/ventilationCardiac arrest requiring CPR/ventilation Bleeding complications Bleeding complications Vascular complications Vascular complications Procedural success Procedural success Duration of hospital stay Duration of hospital stay

Study Definitions Myocardial Infarction 1. < 72 hrs post PCI, baseline CKMB normal CKMB > 3x ULN 2. < 72 hrs post PCI, baseline CKMB high CKMB > 1.5 x baseline 3. > 72 hrs post PCI Elevated Tn with symptoms or ECG changes 4. < 72 hrs post CABG CKMB > 5 x ULN and new Q waves or LBBB 5. Sudden Death Cardiac Arrest with ST elevation/LBBB and/or evidence of thrombus at autopsy/angiography

Study Definitions Prolonged Hypotension  1. Elective IABP MAP 10 mins despite fluids OR new inotropes to maintain MAP >75mmHg  2. No Planned IABP As above OR insertion of IABP to maintain MAP >75mmHg Major bleed  >4g/dl drop in Hb Minor bleed  2-4g/dl drop in Hb

Inclusion Criteria Impaired LV function (EF < 30%) Impaired LV function (EF < 30%) and and Extensive Myocardium at Risk Extensive Myocardium at Risk  BCIS-1 Jeopardy Score > 8  or...Target vessel supplying occluded vessel which supplies >40% of myocardium

Jeopardy Score Califf et al JACC 1985;5: Major Coronary Segments 2 points for each lesion + 2 for each territory distal to lesion

Jeopardy Score BCIS-1 Allows LM and Graft Classification Perera et al AHJ 2009; in press 6 Major Coronary Segments 2 points for each lesion + 2 for each territory distal to lesion Negative points for functioning grafts

Exclusion Criteria Cardiogenic Shock  Systolic BP <85 mmHg despite correction of hypovolemia Acute MI < 48 hours before randomization Planned staged PCI within 28 days Complications of acute MI  VSD, severe MR or intractable VT/VF Contraindication to IABP

BCIS-1 Recruitment Completed 21 st Jan 09 Total 301 patients

Baseline Characteristics IABP N=151 No Planned N=150 Male (%)122 (81.0)117 (78.0) Mean Age (SD)71 (9.3)71 (9.7) Diabetes (%)56 (37.1)50 (33.1) Prior MI (%)113 (74.8)108 (72.9) Prior PCI (%)17 (11.3)14 (9.3) Prior CABG (%)25 (16.6)20 (13.3) NYHA 3/4 (%)99 (66)108 (72) CCS 3/4 (%)72 (48)68 (45.5) GFR median (IQR)58.2 (45.0, 78.6)60.0 (41.9, 80.0)

Inclusion Characteristics IABP N=151 No Planned N=150 Mean E.F. (SD)23.6 (5.2) BCIS-1 Jeopardy Score Mean (SD)10.38 (1.71)10.32 (1.72) 840 (26.5%)42 (28%) 1039 (25.8%)39 (26%) 1271 (47%)68 (45.3%)

Procedural Details IABPNo Planned Elective70 (46%)65 (43%) Urgent/ Emergency81 (53%)85 (57%) Lesions attempted Lesions successfully revasc94.7%94.1% Mean lesions per patient Mean stents per patient GP2b3a use39.3%43.3%

Components of the Primary Outcome: MACCE to Hospital Discharge/ 28 days IABPNo Planned n=151(%)n=150(%) p value* Death3(2.0)1(0.7) 0.40 CVA2(1.3)0(0.0) MI19(11.3)20(13.3) 0.43 Revasc1(0.0)4(1.4) 0.13 Total † † Hierarchical 1 patient had MI and died; 2 patients had MI and PCI * Cox regression

Major Secondary Outcomes IABPNo Plannedp value 6/12 Mortality7 (4.6%)11 (7.3%) 0.32 † Procedural complication2 (1.3)16 (10.7) Access site complication5 (3.3)0 (0)0.06* All bleeds29 (19.3)17 (11.3)0.058 Major bleeds5 (3.3)6 (4.0)0.77 Minor bleeds24 (15.9)11 (7.3)0.021 Procedural success230 (93.5)237 (93.3)0.93 LOS - median days (IQR)2 (1,5)2 (1,4)0.12 †  2 test* Fisher’s exact test

Kaplan Meier 6 month mortality 7.3% vs 4.6%, p = 0.32 Elective IABPNo Planned

IABP Use IABPNo Planned IABP Inserted147 (98%)18 (12%) Reason for Insertion Randomized Allocation1470 Hypotension013 Ventricular Arrhythmia00 Pulmonary Oedema01 Vessel Closure01 Other03 Median duration of use (hrs) (IQR) (6, 23.1)(17.3, 26.4)

IABP Use in No Planned Group IABP inserted as ‘bailout’ in 18 patients (12%) hypotension in 13 (72%) Pulmonary oedema in 1, vessel closure in 1 In these patients: EF % Jeopardy Score ; JS 12 in 13 pts (72%) Duration of IABP: median of 22.9 hrs (vs 8.6 hrs in elective group) MACCE occurred in 4 patients (22%)

Conclusions BCIS have performed the first randomized trial of elective vs. ‘bailout’ IABP in patients with poor LV function and severe coronary disease We did not find evidence that Elective IABP to support high risk PCI is associated with a reduction in MACCE at hospital discharge 12% in the no-planned group required emergency IABP, supporting the important role of provisional IABP use Patients with poor LV function and severe coronary disease treated by PCI appear to have acceptable in-hospital and 6 month mortality (1.3% and 6%)

CenterPrincipal InvestigatorNumber St ThomasRedwood62 BirminghamPitt53 Brightonde Belder32 LeedsBlackman32 LiverpoolStables28 GlasgowOldroyd17 King’s CollegeThomas17 WolverhamptonCotton15 BournemouthSwallow14 BlackpoolRoberts9 LeicesterGershlick4 SouthamptonCurzen4 St GeorgesBrecker4 DorsetWitherow3 ManchesterFrazer3 NottinghamHenderson3 StokeNolan1