Cardiovascular Outcomes in Patients with Drug Eluting Stents Undergoing Non-cardiac

Surgery

Boston Scientific Interventional Fellow, Royal Jubilee Hospital, Victoria, British Columbia

Lecturer in Cardiology, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh

NL Cruden, SA Harding, AD Flapan, C Graham, S Wild, R Slack, J Pell, DE Newby

MY CONFLICTS OF INTEREST ARE

I am currently undertaking an Interventional Fellowship supported by Boston Scientific.

“Trading Restenosis for Thrombosis”

Shuchman. NEJM 2006;355:1949-1952

Non-cardiac Surgery and Stent Thrombosis

Mortality and Non-cardiac SurgeryAuthors Year Type Time Period Patients

(n)DES(%)

Time from PCI to Surgery

Mortality Rate (%)

Kaluza et al 2000 RetrospectiveNon-randomised

1996 - 1998 40 0 <42d 21.4

Wilson et al 2003 RetrospectiveNon-randomised

1990 - 2000 207 0 <60d 3.4

Sharma et al 2004 RetrospectiveNon-randomised

1995 - 2000 47 0 <90d 18.4

Reddy et al 2005 RetrospectiveNon-randomised

1999 - 2004 56 0 ns 8.6

Leibowitz et al 2006 RetrospectiveNon-randomised

1995 - 2002 94 0 <90d 14.6

Vicenzi et al 2006 ProspectiveNon-randomised

2001 - 2004 103 ns <1y 5.7

Compton et al 2006 RetrospectiveNon-randomised

2003 - 2006 38 100 ns 2.5

Schouten et al 2006 RetrospectiveNon-randomised

1999 - 2005 192 52 <2y 3.1

Nuttall et al 2008 RetrospectiveNon-randomised

1990 - 2005 899 0 <1y 3.4

Rabbitts et al 2008 RetrospectiveNon-randomised

2003 - 2006 520 100 <2y 2.6

Adapted from Riddell et al. Circulation 2007;116:e378-382.

Adapted from Rabbitts et al. Anesthesiology 2008;109:596-604.

Aims

• To compare ischaemic cardiac outcomes in patients treated with DES or BMS undergoing non-cardiac surgery

• To examine the relationship between time from stent implantation to non-cardiac surgery and peri-operative cardiac outcomes

Methods

• Record Linkage

• Scottish Coronary Revascularisation Register

• Scottish Hospital Admissions Database– Patients undergoing PCI in Scotland between 1st

April 2003 and 31st March 2007 who subsequently underwent non-cardiac surgery.

• Follow-up until 31/07/2007

Methods

• Primary Endpoint:– In-hospital Death, MI or any IHD event (defined by

ICD code)

• Secondary Endpoints– In-hospital Death– In-hospital MI (defined by ICD code)

• Data analysis– Unpaired t-test or Mann-Whitney– Chi-squared or Fishers exact test– Multivariate Logistical Regression Model

Results

• 17,799 patients underwent 19,541 PCIs

• 1,953 patients who received a coronary stent subsequently underwent non-cardiac surgery

• At least 1 DES – 570 patients

• BMS alone - 1383 patients

Patient DemographicsAll BMS DES P

n=1953 n=1383 n=570Age, years [mean (SD)] 64 (10) 64 (10) 63 (11) 0.1

Male Sex 1267 (65%) 905 (65%) 362 (64%) 0.4

Diabetes Mellitus 287 (20%) 166 (18%) 121 (27%) <0.0001

Current Smokers 561 (30%) 385 (30%) 561 (33%) 0.1

Hypertension 990 (54%) 675 (52%) 315 (58%) <0.01

Previous Myocardial Infarction 605 (33%) 413 (32%) 192 (33%) 0.1

Peripheral Vascular Disease 139 (18%) 91 (18%) 48 (19%) 0.2

Renal Impairment 70 (4%) 43 (3%) 27 (5%) 0.1

Family History of IHD 680 (38%) 483 (38%) 197 (37%) 0.7

Previous CVA/TIA 113 (6%) 77 (6%) 36 (7%) 0.5

Previous CABG 204 (11%) 139 (10%) 65 (12%) 0.3

LVEF <30% 18 (1%) 15 (1%) 3 (<1%) 0.6

Indication

ACS 887 (45%) 655 (47%) 232 (41%) <0.001

Stable IHD 1066 (55%) 728 (53%) 338 (59%)

Index Procedural VariablesAll BMS DES P

n=1953 n=1383 n=570

Lesion Site LMS 35 (2%) 10 (1%) 25 (4%) 0.5RCA 645 (33%) 490 (35%) 155 (27%)

LAD 760 (39%) 492 (36%) 268 (47%)LCx 449 (23%) 338 (24%) 111 (20%)

Grafts 64 (3%) 53 (4%) 11 (2%)Number of stents 1 1575 (81%) 1151 (83%) 424 (74%) <0.0001

≥2 378 (19%) 232 (17%) 146 (24%)Stent Diameter (mm) ≤2.5 257 (13%) 104 (8%) 153 (27%) <0.0001

2.75 261 (14%) 143 (10%) 118 (21%)3.0 772 (40%) 576 (42%) 196 (34%)

3.5 471 (24%) 381 (27%) 90 (16%)4.0 + 192 (10%) 179 (13%) 13 (2%)

Length of Lesion (mm) <10 745 (38%) 585 (42%) 160 (28%) 0.810 to 20 765 (39%) 570 (41%) 195 (34%)

>20 443 (23%) 228 17%) 215 (38%)Lesion Calcification none 1703 (87%) 1220 (88%) 483 (85%) 0.01

moderate 189 (10%) 130 (9%) 59 (10%)severe 61 (3%) 33 (3%) 28 (5%)

Bifurcation Lesion 191 (10%) 132 (10%) 61 (11%) 0.4Ostial Location 101 (5%) 62 (5%) 39 (7%) <0.05

Chronic Total Occlusion 41 (2%) 16 (1%) 25 (4%) <0.0001Glycoprotein IIb/IIIa inhibitor 622 (32%) 431 (32%) 191 (34%) 0.8

In-hospital Cardiac OutcomesInterval between PCI and non-cardiac surgery (Mean ± SD)

BMS - 577 ± 401 daysDES - 427 ± 294 days

P=0.3

P=0.8 P=0.3

In-hospital Outcomes and Timing of Surgery

<42 days 42 days – 1 year >1 year P

n= 40 n=477 n=866

Death/Any IHD event 18 (45%)* 65 (13.6%)* 101 (11.7%)* <0.001

BMS

Death 2 (5%)† 5 (1%)† 1 (0.1%)† <0.0001

Myocardial Infarction 3 (7.5%)‡ 3 (0.6%)‡ 4 (0.5%)‡ <0.0001

<42 days 42 days – 1 year >1 year P

n= 19 n=255 n=282

Death/Any IHD event 7 (36.8%)* 41 (16.1%)* 35 (12.4%)* <0.01

DES Death 1 (5.3%)† 2 (0.8%)† 1 (0.4%)† <0.05

Myocardial Infarction 2 (10.5%)‡ 2 (0.8%)‡ 3 (1.1%)‡ <0.005

*p=0.7, †p=1.0, ‡p=1.0, BMS versus DES

Multivariate AnalysisPredictors of Death or IHD

• Previous Coronary Bypass Grafting OR 1.55 [1.07-2.26]

• Increasing Age OR 1.22 [1.06-1.39] for every 10 years

When is it safe to operate?

Summary

• The risk of ischaemic cardiac events in patients with DES undergoing non-cardiac surgery does not differ from patients treated with BMS.

• In keeping with previous data, peri-operative cardiovascular risk is greatest where surgery is performed within 4-6 weeks of coronary stent implantation.

Limitations

• Retrospective

• Non-randomised

• No data on anti-platelet therapy

Thank you

Scott Harding

Andrew Flapan

David Newby

Contributors to the Scottish Revascularisation Register (R Slack, J Pell)

WTCRF Edinburgh (C Graham, S Wild)

Chief Scientist Office (Health Services Research Grant CZG/2/375)

Surgical Procedures by Type

Primary Stent Type Frequency Percentage

CYPHER 140 24.6

TAXUS 389 68.2

ENDEAVOUR 27 4.8

DES NOT SPECIFIED 14 2.4

Drug Eluting Stents Used

Power Calculation

• Based on observed event rate of 10% in patients with BMS undergoing non-cardiac surgery and assuming a sample size of 1000 (n=500 in DES and BMS groups respectively)

• This study would have 80% power to detect a 5% absolute difference in the combined primary endpoint between the BMS and DES groups at the 0.05 significance level.

Codes Used

• ICD Codes• Acute myocardial infarction I210, I211, I212, I213, I214, I219, I220, I221, I228, I229

• Any IHD Event As above plus

Unstable angina I200, I201, I208, I209

Coronary thrombosis I240

Acute Ischaemic heart disease I249

Atherosclerotic heart disease I250, I251

• OPCS CodesA01-52, 57-69, 75; B1-31, 33-40; C1, 2, 5-9, 31-37; D1, 3, 10-12, 16-17; E1-4, 7, 8, 14-24, 39-41, 43-47, 53-58, 61; G1-13, 23-41, 49-53, 57-63, 68-74, 76-78; H1-19, 33-42, 57-61, 66; J1-5, 7-9, 18-23, 27-37, 54-65, 69-73; L1, 2, 4-8.4, 9-12, 16-25, 29, 30, 33-34, 37, 38, 41, 42, 45, 46, 48-53, 56-62, 65, 67, L68, 70, 74, 75.1, 77, 80 (NOT 80.3 OR 80.4), 81-85, 87, 90, 93, 98; M1-6, 8, 18-25, 34-41, 51, 52, 54, 55, 61-64, 72-75; N1, 5-9, 26, 28; P17, 18, 21-25, 32; Q1, 7-10, 20-39, 43-49, 52-54; R17; S1-3, S17-28, 33-39; T1-11, 15-27, 29, 30, 33-43, 50-77, 64-72, 76-80, 85-89, 92; V1-47, 49, 52-57; W1-34, 37-81, 82-89, 93-99; O6-10; X1-27

In-hospital Outcomes & Timing of SurgeryDeath or any IHD Event

Death Myocardial Infarction

BMS

DES

Chi-Square df pStent type 0.7 1 0.403Lesion 4.125 4 0.389Primary diagnosis 10.737 9 0.294No. stents [1, >1] 0.657 1 0.418Stent diameter 7.745 5 0.171Length of lesion 2.926 2 0.232Lesion Calcification 0.475 2 0.789Birfucation 1.461 1 0.227Ostial location 0.721 1 0.396Indication 5.307 7 0.623Procedure status 5.026 3 0.17Sex 0.283 1 0.595Diabetic 2.317 1 0.128Smoker 2.8 2 0.247Hypertension 0.176 1 0.675Previous MI 2.063 1 0.151PAD 0.613 1 0.434Renal status 6.026 3 0.127Fam. Hist. CAD 1.21 1 0.271LVEF 1.575 2 0.455GPIIbIIIa use 2.983 4 0.561Urgency of Surgery 3.612 1 0.057Vessel occlusion 6.039 2 0.049Previous CABG 7.128 1 0.008

T-Test No Event Death/IHD Event

p

Mean age, yrs (SD) 63.5 (10.3) 65.5 (9.5) 0.001

Univariate Predictors of Death/IHD