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

Transcription

1 The German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients (GOPCABE) Study Prof. Dr. med. Anno Diegeler Bad Neustadt Heart Center For the GOPCABE study group

2 Disclosures Sponsor of the study is the German Society of Thoracic and Cardiovascular Surgery (DGTHG) Unrestricted grant ( Euro) from Maquet Inc. Rastatt Germany Payment exclusively for web-based data management of the IKKF (Institut für klinischkardiovaskuläre Forschung), Munich

3 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 * ROOBY 1 ; CORONARY 2 ; BEST SURGICAL REVASCULARIZATION 3 1 N Engl J Med 2009; 361: N Engl J Med 2012; 366: Circulation 2010; 121:

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5 Patients 75 years All comers screened The GOPCABE Trial Features 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

6 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

7 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

8 patients > 75 years with isolated first-time CABG n = 4355 potentially eligible patients n = 3683 Randomization n = 2539 (69%) 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) off-pump CABG (n = 1271) On-pump CABG (n = 1268) exclusion after randomization (n = 80) exclusion after randomization (n = 56) - additional cardiovascular procedure (n = 20) - urgent operation (n = 9) - no surgery performed (n = 16) - withdrawn consent (n = 19) - miscellaneous (n = 16) isolated CABG performed by assigned surgeon (n = 1191) isolated CABG performed by assigned surgeon (n = 1212) - 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) - lost to follow-up (n = 3) - withdrawn consent (n = 1) - lost to follow-up (n = 4) - withdrawn consent (n = 1) available for analysis at 30 days (n = 1187) available for analysis at 30 days (n = 1207) - lost to follow-up (n = 8) - lost to follow-up (n = 15) - withdrawn consent (n = 1) available for analysis at 12 months (n = 1179) available for analysis at 12 months (n = 1191)

9 baseline characteristics [No (%)] on-pump off-pump baseline characteristics [No (%)] on-pump off-pump n = 1207 n = 1187 female gender 389 (32.2) 366 (30.8) age [years] 78.4 ± ± 2.98 body mass index [kg / m 2 ] 27.8 ± ± 4.1 left ventricular ejection fraction CCS angina grading scale < 30% 39 (3.2) 25 (2.1) 30-50% 341 (28.3) 365 (30.7) > 50% 827 (68.5) 797 (67.1) I 230 (19.0) 224 (18.9) II 425 (35.2) 396 (33.4) insulin-dependent diabetes mellitus 166 (13.8) 179 (15.1) III 496 (41.1) 523 (44.1) 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) extent of coronary artery disease IV 56 (4.6) 44 (3.7) 1 vessel 14 (1.2) 23 (1.9) 2 vessel 106 (8.8) 119 (10.0) 3 vessel 730 (60.5) 712 (60.0) previous percutaneous coronary intervention 263 (21.8) 268 (22.6) left main disease vessel 357 (29.6) 333 (28.1) 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) renal replacement therapy 11 (0.9) 11 (0.9) critical condition 36 (3.0) 22 (1.9) logistic EuroSCORE 8.23 ± ± 7.17

10 off-pump (n = 1187) No. (%) on-pump (n = 1207) mean number of anticipated grafts * anticipated number of grafts 1 28 (2.4%) 12 (1%) (20.4%) 260 (21.5%) (59%) 683 (56.6%) (16.6%) 222 (18.4%) >4 20 (1.7%) 30 (2.5%) mean number of performed grafts *** number of performed grafts *** 1 74 (6.2 %) 44 (3.6 %) (34.9 %) 382 (31.6 %) (46.9 %) 551 (45.7 %) (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 %)

11 Cross-over by conversion off-pump n = 116 (9.7%) before skin incision on-pump n = 62 (5.1%) - hemodynamic instability / unstabe angina (n = 6) - logistic reasons (n = 52) - unknown (n = 3) 61(5.1%) - calcified ascending aorta (n = 13) - logistic reaosons (n = 21) - unknown (n = 2) 36(2.9%) before first anastomosis 34(2.8%) - hemodynamic instability / 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) 61(2.1%) after first anastomosis 21(1.8%) - 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)

12 Primary endpoint 30 days after surgery modified intention to treat analysis 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 [ ] 0.74 death within 30 days after surgery 31 (2.6%) 34 (2.8%) 0.92 [ ] 0.75 myocardial infarction 18 (1.5%) 20 (1.7%) 0.92 [ ] 0.79 stroke 26 (2.2%) 32 (2.7%) 0.83 [ ] 0.47 repeat revascularization 15 (1.3%) 5 (0.4%) 2.42 [ ] 0.04 new renal replacement therapy 29 (2.4%) 37 (3.1%) 0.80 [ ] 0.36

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

14 Primary endpoint 30 days after surgery Per protocol analysis 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 [ ] 0.40 death within 30 days after surgery 22 (2.1%) 31 (2.7%) 0.76 [ ] 0.32 myocardial infarction 13 (1.2%) 19 (1.7%) 0.77 [ ] 0.42 stroke 20 (1.9%) 32 (2.8%) 0.68 [ ] 0.17 repeat revascularization 14 (1.3%) 4 (0.3%) 2.65 [ ] 0.03 new renal replacement therapy 24 (2.2%) 33 (2.9%) 0.80 [ ] 0.40

15 Secondary endpoints use of resources: Off-pump On-pump 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)

16 12 months follow-up 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 [ ] 0,483 death within one year after surgery 83 (7.0) 95 (8.0) 0.88 [ ] myocardial infarction 25 (2.1) 28 (2.4) 0.90 [ ] stroke 41 (3.5) 52 (4.4) 0.79 [ ] repeat revascularization 36 (3.1) 24 (2.0) 1.52 [ ] new renal replacement therapy 34 (2.9) 42 (3.5) 0.82 [ ] 0.375

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23 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

24 Conclusion In a randomized trial comparing off- pump and onpump coronary bypass surgery we did not find a significant difference in clinical outcome at 30 days and at 12 months