Renal Function After Off-Pump CABG: Journal Club For educational use only

1. Kidney function after off-pump or
on-pump coronary artery bypass
graft surgery
Wisit Cheungpasitporn
October 3, 2014

2. Disclosure
• None

3. Coronary Revascularization - Surgical
Historical Review:
• 1946 Vineberg IMA implant into cardiac muscle
• 1954 Murray Experimental anastomosis (IMA/SVG)
• 1962 Sabiston First CABG (SVG to RCA)
• 1964 Garrett First CABG to LAD without pump
• 1967 Kolessov Lima-LAD, thoracotomy
• 1968 Favaloro Initial experience with SVG with pump
• 1970 Johnson Expanded experience CABG
• 1972 Ankeney USA 1st Single graft series w/o CPB

4. Classic Procedure- CABG
1. Sternotomy
2. IMA Harvest
3. SVG
4. Cannulation for CP Bypass
5. Arrest Heart
6. Anastomosis Heparin
7. Wean From Bypass
8. Reverse heparin and
Stop Bleeding

5. On-pump CABG

6. On-pump CABG
Geissler H J et. al. MMCTS 2006

7. On-Pump CABG
Consumption of coagulation factors Bleeding
Platelet damage
Leukocyte damage (pyrogen) Fever
Leukocyte & platelet-mediated
endothelial damage Edema
Complement-induced increased
vascular permeability
Bradykinin Vasoconstriction
Platelet & fibrin microemboli Organ dysfunction
Sellke FW et. al. Circulation. 2005

8. Sellke FW et. al. Circulation. 2005

9. Off-pump CABG- (OPCAB) tissue stabilization and heart positioning devices.
Verma S et al. Circulation. 2004;109:1206-1211

10. Conventional coronary bypass surgery Beating Heart Coronary Surgery
Heart lung machine
Myocardial protection
Stopping the heart
Verma S et al. Circulation. 2004;109:1206-1211

11. • Click here to watch a short clip

12. OPCAB- “beating heart surgery”
• Extensive ascending aortic atheromatous or calcific
changes
• In U.S., OPCAB ~ 25% in 2001 of isolated CABG and
has not changed since then.
• Disadvantage
• Incomplete revascularization if exposure of the back
of the heart is challenging
• Decreased graft patency because of suboptimal
conditions during the construction of the distal
anastomosis.
Lazar HL et. al. Circulation. 2013;128(4):406-13

13. Relative Contraindications- OPCAB
- Intramyocardial Coronary a.
- Very small arteries
- Calcified arteries.
- Hemodynamic Instability/Ischemia.
- Cardiogenic shock.
Lazar HL et. al. Circulation. 2013;128(4):406-13

14. Møller CH et. al. Cochrane Database Syst Rev. 2012

15. Møller CH et. al. Cochrane Database Syst Rev. 2012

16. Møller CH et. al. Cochrane Database Syst Rev. 2012

18. Seabra VF et al. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.

19. Seabra VF et al. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.

20. Seabra VF et al. Clin J Am Soc Nephrol. 2010 Oct;5(10):1734-44.

21. GOPCABE study
• Patients
• 75 years or older with
elective first time CABG
• 2539 patients randomized
• Intervention
• Off-pump vs On-pump
CABG
• Outcomes
• Composite of death, MI,
stroke, revascularization,
new RRT
OR = 0.95 (0.71-1.28) for 30 days
OR = 0.93 (0.76-1.16) for 12 months
Diegeler et al. NEJM. 2013

22. GOPCABE study
• 1612 (67%) had available data on kidney function
AKI: 47.3% for off-pump vs 52.7% for on-pump (p = 0.17)
Reents et al. Ann Thorac Surg. 2014
CKD

23. Lamy A et. al. NEJM. 2012.

24. CORONARY TRIAL
• RCT with blinded adjudicated outcome assessment
• Off pump vs On pump CABG
• Randomization
• 24-hour automated voice-activated telephone service
• All patients and investigators - aware of study assignments
• Primary outcomes
• Composite of death, nonfatal stroke, nonfatal MI, new renal failure
requiring dialysis
• An adjudication committee whose members were unaware of study-group
assignment

25. Participants
Inclusion criteria
• Isolated CABG with median
sternotomy
• One of the following:
• PVD
• Stroke
• Renal insufficiency
• Age ≥ 70 yr
• If < 70 years
• ≥ 1 risk factor if 60-69 yr
• ≥ 2 risk factors if 55-59 yr
• Risk factor – DM, urgent, smoker,
LVEF ≤ 35%
Exclusion criteria
• Planned additional cardiac procedure
• Contraindication to off-pump or on-pump
CABG
• Life expectancy < 2 years
• Emergency or re-do CABG

26. 4752 patients from 79 sites in 19 countries
Netherlands (27)
Sweden (56)
United Kingdom (227)
France (4)
Italy (48)
November 2006 – October 2011
Argentina (257)
Canada (830)
Brazil (358)
USA (68)
Czech Republic (298)
Estonia (91)
Turkey (132)
Ukraine (11)
Colombia (57)
Australia (29)
Uruguay (34)
China (781)
India (1307)
Chile (137)

27. Lamy A et al. N Engl J Med 2012;366:1489-1497.
Crossover
7.9%
Crossover
6.4%

28. Result – 30 days
Lamy A et al. N Engl J Med 2012;366:1489-1497.

29. AKIN stage 1 = 50% increase from baseline or increase ≥ 0.3 mg/dL within 48 hours

30. Result – 1 year
Lamy A. et. al. NEJM 2013

31. Lamy A. et. al. NEJM 2013

32. JAMA, 311: 2191-2198, 2014.

33. OBJECTIVES
• To characterize the risk of acute kidney injury with an
intervention in a randomized clinical trial.
• To determine if there is a difference between the 2
treatment groups in kidney function 1 year later.

34. Study design and setting
• Substudy of CORONARY trial
• 69 of 79 study sites participated
• January 2010 – June 2011
• Each site randomized into the protocol
4752 patients in CORONARY trial
1777 excluded
-1336 from participating sites prior to substudy initiation
-441 from nonparticipating sites
2975 patients enrolled

35. Patients
• Per the CORONARY trial
• Additional exclusion
• ESRD - eGFR < 15 ml/min/1.73m2 or chronic dialysis
• No SCr before randomization

36. Outcomes
• Postoperative AKI
• > 50% increase in SCr from baseline within 30 days of CABG
• Baseline SCr obtained within 7 days before randomization
• Highest SCr within 30 days after surgery was assessed for AKI
• Loss of kidney function at 1 year
• > 20% loss in eGFR from baseline
• SCr at 1 year was measured
• CKD-EPI for eGFR

37. Statistical analysis
• Logistic regression – Relative risk
• Adjusted analysis for pre-specified covariates assessed prior surgery
• Age
• Sex
• LV function
• DM
• Long-term use of ACEI or ARB
• Statin use
• Diuretic use
• Urgent/elective surgery
• CKD (eGFR ≤ 60 ml/min/1.73m2)
• Subgroup analysis by CKD

38. Statistical analysis
• With the enrollment of 2932 patients
• > 80% power to detect 25% RR reduction in kidney function
loss at 1 year
• Missing data
• SCr – carried forward the prerandomization SCr
• eGFR at 1 year
• ESRD patients (≥ 3 mo of dialysis) or died shortly after
acute dialysis for severe AKI  5 ml/min/1.73 m2

39. Result
2975 patients enrolled
2932 patients included
43 excluded
-39 ESRD
-4 missing SCr before surgery
1472 off-pump CABG 1460 on-pump CABG
102 (6.9%) in off-pump group underwent on-pump CABG
105 (7.2%) in on-pump group underwent off-pump CABG

41. Result – postoperative AKI
In survivors, most patients with AKI no longer met the definition
169/236 (72%) in off-pump vs 180/280 (64%) in on-pump (p=0.08)

42. Result – kidney function loss at 1 year
Off pump On pump P-value
Mean eGFR at 1 year 72±19 73±19 NS
Mean absolute change in eGFR -3±16 -2±16 0.04

43. Subgroup analysis
CKD Non-CKD
Absolute risk reduction
for AKI
-11% (-17.4, -4.6) -1.1% (-4.2, 2.1)

44. Complete Case As-Treated Analysis

45. Observational Cohort Analysis
Kidney function loss at 1 year: 32.1% in AKI vs 12.5% in non-AKI patients
Adjusted OR = 3.37 (95% CI, 2.65-4.28); p < 0.001

46. Discussion
• Off-pump CABG reduces the risk of AKI
• Benefit was higher in pts with preoperative CKD
• An intervention that prevents AKI better preserves long-term kidney
function – remain unproven in RCT
• Too small magnitude of AKI reduction with off-pump CABG and affect
too few patients to have an effect on long-term kidney function
• Too short follow-up
• Errors with SCr as a measure of kidney function
• Differential care in follow-up between off- and on-pump CABG
• Mild to moderate AKI may not cause substantial CKD

47. Limitations
• Multiple measurement of kidney function over time both
before and long after AKI
• Use of new markers of kidney function or injury
• Enroll a greater number of pts with baseline CKD
• a causal relationship between AKI and long-term kidney
function more likely to observed if exist

48. Strengths of this study
• Largest AKI prevention trial conducted to date.
• International recruitment across 19 countries will
provide generalizable estimates of the treatment effect
• Use of a rigorous randomized trial method
• concealed allocation
• blinded central adjudication of outcomes
• No evidence of differential ascertainment of kidney
outcomes in two surgical groups
• Complete follow-up
• >90% had 1-year SCr measured

49. Conclusion
• The use of off-pump vs on-pump CABG surgery
• Reduced the risk of postoperative AKI;
• Failed to observe better kidney function with off-pump
vs on-pump CABG surgery 1 year later.

50. Questions & Discussion