The German Off-Pump Coronary Artery Bypass Grafting …clinicaltrialresults.org/Slides/ACC 2013/Diegeler_GOPCABE_ ACC 2013... · For the GOPCABE study group The German Off-Pump Coronary

For the GOPCABE study group

The German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients (GOPCABE) Study

Prof. Dr. med. Anno Diegeler Bad Neustadt Heart Center

German Off-Pump CABG in Elderly Trial (GOPCABE) Prof. Dr. Anno Diegeler

Herz- und Gefäß-Klinik

Bad Neustadt a. d. Saale

Sponsor of the study is the German Society of Thoracic and Cardiovascular Surgery (DGTHG)

Unrestricted grant (≅250.000 Euro) from Maquet™ Inc. Rastatt Germany

Payment exclusively for web-based data management of the IKKF™ (Institut für klinisch- kardiovaskuläre Forschung), Munich

Disclosures




There are some rationales, that avoiding the heart-lung machine in coronary bypass surgery reduces invasiveness and by this has a clinical benefit on major adverse events (MACCE)

However…

Background

Several randomized trials* with different patient characteristics could not confirm a significant difference * ROOBY1; CORONARY2; BEST SURGICAL REVASCULARIZATION3

1 N Engl J Med 2009; 361: 1827 – 37 2 N Engl J Med 2012; 366: 1489 – 97

3 Circulation 2010; 121: 498 - 504







The GOPCABE –Trial Features

• Patients ≥ 75 years

• All comers screened

• 12 German Centers with high experience level for both techniques

• Nominated Surgeons for both techniques

• Screening log for excluded patients

Enrollement between 6/2008 and 9/2011




Patient exclusion criteria

• Additional cardiac disease necessitating additional surgery

• Previous pericardiotomy

• Immediate surgery i.e. within 24 hours after admission

• Inability or unwillingness to provide consent

Anatomy , morphology of the coronary artery or left

ventricular function was not an exclusion criteria




Outcome Features

Hypothesis: Off pump is not able to reduce a combined endpoint MACCRE to 30%; OR 0.63 with a power of 90%

MACCRE: death, myocardial infartion, additional revascularization, stroke, new onset renal replacement therapy

Primary endpoint: at 30 days after surgery

Secondary endpoints: 12 months MACCRE; Ventilation time, stay on ICU, hospital stay, resources utilization




patients > 75 years with isolated first-time CABG

n = 4355

exclusion criteria:

- urgent operation (n = 526)

- inability to provide consent (n = 122)

- participation in another study (n = 24)

- unwillingness to provide consent

(n = 537)

- logistic reasons (n= 607)

Randomization

n = 2539 (69%)

exclusion after randomization

(n = 80)

- additional cardiovascular

procedure (n = 20)

- urgent operation (n = 9)

- no surgery performed (n = 16)

- withdrawn consent (n = 19)

- miscellaneous (n = 16)

exclusion after randomization (n = 56) - additional cardiovascular procedure (n = 21) - urgent operation (n = 6) - no surgery performed (n = 11) - withdrawn consent (n = 11) - missing consent form (n = 1) - death before surgery (n = 1) - miscellaneous (n = 5)

available for analysis at 30 days (n = 1187)

- lost to follow-up (n = 3)


available for analysis at 30 days (n = 1207)




available for analysis at 12 months (n = 1179)

potentially eligible patients

n = 3683

On-pump CABG (n = 1268) off-pump CABG (n = 1271)

isolated CABG performed by

assigned surgeon (n = 1191)

isolated CABG performed by

assigned surgeon (n = 1212)



available for analysis

at 12 months (n = 1191)




baseline characteristics [No (%)] on-pump off-pump

n = 1207 n = 1187

female gender 389 (32.2) 366 (30.8)

age [years] 78.4 ± 2.87 78.6 ± 2.98

body mass index [kg / m2] 27.8 ± 4.1 27.8 ± 4.1

insulin-dependent diabetes mellitus 166 (13.8) 179 (15.1)

chronic obstructive pulmonary disease

118 (9.8) 127 (10.7)

previous stroke 95 (7.9) 121 (10.2)

peripheral vascular disease 392 (32.5) 388 (32.7)

pulmonary arterial hypertension 26 (2.2) 39 (3.3)

previous myocardial infarction 456 (37.8) 427 (36.0)

previous percutaneous coronary intervention 263 (21.8) 268 (22.6)

history of atrial fibrillation 190 (15.7) 177 (14.9)

implanted pacemaker 33 (2.7) 31 (2.6)

creatinine level < 2.3 mg/dl 1169 (96.9) 1150 (96.9)

> 2.3 mg/dl 27 (2.2) 26 (2.2)

baseline characteristics [No (%)] on-pump off-pump

left ventricular ejection fraction

< 30% 39 (3.2) 25 (2.1)

30-50% 341 (28.3) 365 (30.7)

> 50% 827 (68.5) 797 (67.1)

CCS angina grading scale

I 230 (19.0) 224 (18.9)

II 425 (35.2) 396 (33.4)

III 496 (41.1) 523 (44.1)

IV 56 (4.6) 44 (3.7)

extent of coronary artery disease

1 vessel 14 (1.2) 23 (1.9)

2 vessel 106 (8.8) 119 (10.0)

3 vessel 730 (60.5) 712 (60.0)

left main disease + 1 – 3 vessel 357 (29.6) 333 (28.1)

renal replacement therapy 11 (0.9) 11 (0.9)

critical condition 36 (3.0) 22 (1.9)

logistic EuroSCORE 8.23 ± 6.61 8.31 ± 7.17




Operative variables and use of resources

off-Pump

(n = 1187) on-Pump

(n = 1207)

No. (%)

mean number of anticipated grafts * 2.95 3

anticipated number of grafts

1 28 (2.4%) 12 (1%)

2 242 (20.4%) 260 (21.5%)

3 700 (59%) 683 (56.6%)

4 197 (16.6%) 222 (18.4%)

>4 20 (1.7%) 30 (2.5%)

mean number of performed grafts *** 2.66 2.84

number of performed grafts ***

1 74 (6.2 %) 44 (3.6 %)

2 414 (34.9 %) 382 (31.6 %)

3 557 (46.9 %) 551 (45.7 %)

4 123 (10.4 %) 187 (15.5 %)

> 4 19 (1.6 %) 43 (3.5 %)

anticipated vs. performed grafts per patient ***

no. anticipated = No. performed 663 (56%) 651 (54 %)

no. anticipated < No. performed 121 (10 %) 202 (17 %)

no. anticipated > No. performed 403 (34 %) 354 (29 %)




on-pump

n = 62 (5.1%) off-pump

n = 116 (9.7%)

before first anastomosis

before skin incision

after first anastomosis

Cross-over by conversion

- hemodynamic instability

/ myocardial ischemia (n = 16)

- diffuse calcified small vessel (n = 1)

- intramyocardial vessel (n = 1)

- pericardial adhesion / inadequate

vessel exposure (n = 1)

- revision of coronary anastomosis (n = 2)

21(1.8%)

- calcified ascending aorta (n = 13)

- logistic reaosons (n = 21)

- unknown (n = 2)


/ unstabe angina (n = 6)

- logistic reasons (n = 52)

- unknown (n = 3)

61(5.1%)

36(2.9%)


/ myocardial ischemia (n = 17)

- diffuse calcified small vessel (n = 6)

- intramyocardial vessel (n = 3)

- pericardial adhesion / inadequate

vessel exposure (n = 3)

- bleeding / myocardial injury (n = 2)

- unknown (n = 3)

- calcified ascending aorta (n = 24)

- miscellaneous (n = 2)

34(2.8%)

61(2.1%)




primary endpoint [no (%)] off-pump on-pump odds ratio

[95% CI] p value

30 days after surgery n = 1187 n = 1207

composite 93 (7.8%) 99 (8.2%) 0.95 [0.71 – 1.28] 0.74

death within 30 days after surgery 31 (2.6%) 34 (2.8%) 0.92 [0.57 – 1.51] 0.75

myocardial infarction 18 (1.5%) 20 (1.7%) 0.92 [0.51 – 1.66] 0.79

stroke 26 (2.2%) 32 (2.7%) 0.83 [0.50 – 1.38] 0.47

repeat revascularization 15 (1.3%) 5 (0.4%) 2.42 [1.03 – 5.72] 0.04

new renal replacement therapy 29 (2.4%) 37 (3.1%) 0.80 [0.49 – 1.29] 0.36

modified intention to treat analysis

Primary endpoint 30 days after surgery




Composite endpoint (death, myocardial infarction, stroke, repeat revascularisation, new renal replacement therapy) within 30 days after surgery according to center




primary endpoint [no (%)] off-pump on-pump odds ratio p value

30 days after surgery n = 1071 n = 1145 [95% CI]

composite 75 (7.0%) 92 (8.0%) 0.87 [0.63 – 1.20] 0.40

death within 30 days after

surgery 22 (2.1%) 31 (2.7%) 0.76 [0.44 – 1.31] 0.32

myocardial infarction 13 (1.2%) 19 (1.7%) 0.77 [0.40 – 1.47] 0.42

stroke 20 (1.9%) 32 (2.8%) 0.68 [0.39 – 1.18] 0.17

repeat revascularization 14 (1.3%) 4 (0.3%) 2.65 [1.10 – 6.40] 0.03

new renal replacement therapy 24 (2.2%) 33 (2.9%) 0.80 [0.48 – 1.34] 0.40

Primary endpoint 30 days after surgery

Per protocol analysis




use of resources:

patients with allogenic blood transfusion *** 668 (56.3%) 757 (62.7%)

units of transfused packed red blood cells† *** 2 (1) 2.4 (2)

operative time [min]† 175 (170) 174 (168)

duration of mechanical ventilation [hours]† 25.1 (12) 30.7 (12)

postoperative length of stay ICU [days]† 3.7 (2) 4.3 (2)

postoperative length of stay hospital [days]† 11.5 (9) 11.6 (9)

Secondary endpoints

Off-pump On-pump




primary endpoint [no (%)] off-pump on-pump hazard ratio

[95% CI] p value

12 months after surgery n = 1179 n = 1191

composite 154 (13.1) 167 (14.0) 0.93 [0.76 – 1.16] 0,483

death within one year after surgery 83 (7.0) 95 (8.0) 0.88 [0.65 . 1.18] 0.383

myocardial infarction 25 (2.1) 28 (2.4) 0.90 [0.53 – 1.54] 0.701

stroke 41 (3.5) 52 (4.4) 0.79 [0.53 – 1.19] 0.260

repeat revascularization 36 (3.1) 24 (2.0) 1.52 [0.90 – 2.54] 0.112

new renal replacement therapy 34 (2.9) 42 (3.5) 0.82 [0.52 – 1.28] 0.375

12 months follow-up






















Limitation

• Modified intention to treat analysis

• Nomitation of a surgeon creates a time interval before surgery and more cross overs

• Only local data confirmation performed

• Minor events such as neurocognitive impairments or graft patency not evaluated




Conclusion

In a randomized trial comparing off- pump and on-pump coronary bypass surgery we did not find a

significant difference in clinical outcome at 30 days and at 12 months

Documents

The German Off-Pump Coronary Artery Bypass Grafting …clinicaltrialresults.org/Slides/ACC 2013/Diegeler_GOPCABE_ ACC 2013... · For the GOPCABE study group The German Off-Pump Coronary