Kidney function after off-pump or on-pump coronary artery bypass graft surgery

Wisit Cheungpasitporn

October 3, 2014

Disclosure• None

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

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

On-pump CABG

On-pump CABG

Geissler H J et. al. MMCTS 2006

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

Sellke FW et. al. Circulation. 2005

Off-pump CABG- (OPCAB) tissue stabilization and heart positioning devices.

Verma S et al. Circulation. 2004;109:1206-1211

Heart lung machineMyocardial protection

Stopping the heart

Conventional coronary bypass surgery Beating Heart Coronary Surgery

Verma S et al. Circulation. 2004;109:1206-1211

• Click here to watch a short clip

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

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

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

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

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

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

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

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

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

Diegeler et al. NEJM. 2013

OR = 0.95 (0.71-1.28) for 30 daysOR = 0.93 (0.76-1.16) for 12 months

GOPCABE study

• 1612 (67%) had available data on kidney function

Reents et al. Ann Thorac Surg. 2014

AKI: 47.3% for off-pump vs 52.7% for on-pump (p = 0.17)

CKD

Lamy A et. al. NEJM. 2012.

• 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

CORONARY TRIAL

ParticipantsInclusion 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

4752 patients from 79 sites in 19 countries

Argentina (257)

Canada (830)

Brazil (358)

Netherlands (27)Sweden (56)

United Kingdom (227)France (4)Italy (48)

USA (68)

Czech Republic (298)Estonia (91)Turkey (132)Ukraine (11)

Colombia (57)

Australia (29)

Uruguay (34)

China (781)

India (1307)

Chile (137)

November 2006 – October 2011

Lamy A et al. N Engl J Med 2012;366:1489-1497.

Crossover7.9%

Crossover6.4%

Result – 30 days

Lamy A et al. N Engl J Med 2012;366:1489-1497.

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

Result – 1 year

Lamy A. et. al. NEJM 2013

Lamy A. et. al. NEJM 2013

JAMA, 311: 2191-2198, 2014.

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.

• Substudy of CORONARY trial

• 69 of 79 study sites participated

• January 2010 – June 2011

• Each site randomized into the protocol

Study design and setting

1777 excluded-1336 from participating sites prior to substudy initiation-441 from nonparticipating sites

4752 patients in CORONARY trial

2975 patients enrolled

Patients

• Per the CORONARY trial

• Additional exclusion• ESRD - eGFR < 15 ml/min/1.73m2 or chronic dialysis• No SCr before randomization

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

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

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

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 CABG105 (7.2%) in on-pump group underwent off-pump CABG

Result – postoperative AKI

In survivors, most patients with AKI no longer met the definition169/236 (72%) in off-pump vs 180/280 (64%) in on-pump (p=0.08)

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

Subgroup analysis

CKD Non-CKD

Absolute risk reduction for AKI

-11% (-17.4, -4.6) -1.1% (-4.2, 2.1)

Complete Case As-Treated Analysis

Observational Cohort Analysis

Kidney function loss at 1 year: 32.1% in AKI vs 12.5% in non-AKI patientsAdjusted OR = 3.37 (95% CI, 2.65-4.28); p < 0.001

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

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

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

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.

Questions & Discussion