Table 1 The most important publications on Off-Pump vs. On-pump, matched with the appropriate “Level of evidence” and “key results” of each individual study

[1] Angelini G et al, Lancet (2002)

RCT, (BHACAS 1)

Less AFib, Inotrop use, Transfusions and hospital stay in Off-pump group. The authors concluded that Off-pump coronary surgery significantly lowers in-hospital morbidity without compromising outcome in the first 1-3 years after surgery compared with on-pump surgery.

200 pts Off pump vs. 201 pts on pump

From 1997 to 1999. Operations performed by experience surgeons.

Aim to assess mortality and cardiac related events at mid-term follow-up (25 months).

[2] Ascione R et al, European heart journal (2004)

RCT, (BHACAS 2)

Both groups showed a similar deterioration of the “quality of life scoring systems” with time.

200 pts Off pump vs. 201 pts on pump

Aim to assess disease specific quality of life at mid-term follow up.

[3] Angelini G et al, J Thorac Cardiovasc Surg (2009)

6 to 8 years follow up of the BHACAS pts.

The likelihood of graft occlusion was no different between off-pump coronary artery bypass (10.6 %) and coronary artery bypass grafting with cardiopulmonary bypass (11.0 %) groups (odds ratio, 1.00; 95 % confidence interval, 0.55-1.81; P > .99).

Aim to assess graft patency (multisliced CT) and MACCE.

There were no differences between off-pump and on pump groups in the hazard of death (hazard ratio, 1.24; 95 % confidence interval, 0.72-2.15) or MACCE (hazard ratio, 0.84; 95 % confidence interval, 0.58-1.24)

[4] Nathoe HM et al, N Engl J Med (2003)

Multicenter RCT.

Graft patency was similar and above 90 % in both groups. Freedom from MACCE was 90 %, somehow similar between the two groups. At 1 year off pump was $1,839 cheaper per pt studied.

Low risk patients predominantly single or double vessel disease. 140 pts either arm of the study.

Graft patency, MACCE and cost-effectiveness in 1 year following surgery, was reported.

[5] Puskas J et al, J Thorac Cardiovasc Surg (2003)

Single-centre RCT.

Number of grafts performed and index of completeness of revascularization were similar.

200 unselected, elective CABGs were randomly assign to Off vs. On pump.

Off pump group has less myocardial enzyme rise, less coagulopathy, less transfusion requirements and shorter intubation time.

From 2000 to 2001.

Operations performed by experience surgeons.

[6] Puskas J et al, JAMA (2004)

1 year Follow-up of the above RCT.

Similar graft patency and MACCE between the 2 groups at 30 days and 1 year. Off pump appeared to be cost-effective.

Graft patency, MACCE and cost-effectiveness, in 30 days and 1 year following surgery was reported.

[7] Puskas J et al, Ann Thorac Surg (2011)

7.5 year Follow-up of the above RCT.

Mortality, around 30 % at 7.5 years in both groups.

Early graft patency was assessed with angiography and late with Multisliced CT.

Graft patency, around 80 % at 7.5 years in both groups.

Late graft patency, recurrence of ischemia and need for re intervention was reported.

Re intervention rate 2.3 % at 7.5 years in both groups.

[8] Legare JF et al, Circulation (2004)

Single-centre RCT.

Excellent postoperative results without significant differences were demonstrated with either procedure.

300 pts divided into two equal arms. Pts with EF < 30 % were excluded.

Postoperative morbidity and mortality was compared between the two groups.

[9] Al-Ruzzeh et al, BMJ (2006)

Single-centre RCT.

Similar graft patency between the two groups at 3 months.

168 pts divided into two equal arms.

Angiographic examination was carried out at three months postoperatively. Neurocognitive tests were carried out at baseline and at six weeks and six months postoperatively.

Interestingly, Scores for neurocognitive function showed a significant difference in three memory subtests at six weeks and two memory subtests at six months in favor of the off-pump group.

[10] ROOBY Trial, N Engl J Med (2009)

Multi-centre RCT.

Similar 30-day composite outcome around 6-7 %. One year composite outcome 9.9 % off-pump vs. 7.4 % on-pump, P = 0.04.

2203 pts randomly assign to either treatment.

Composite of death and complications within 30 days and in 1 year following surgery was investigated.

Off-pump pts had fewer grafts than originally planned.s

The surgeons experience was questioned. The conversion to on pump rate was also questioned.

Early follow-up angiograms showed patency of 82.6 % off-pump vs. 87.8 % on-pump, P < 0.01.

[11] Moller CH et al, Circulation (2010)

Single-centre RCT.

Fewer grafts were performed to the lateral part of the LV wall during off-pump surgery (0.97 versus 1.14 after on-pump surgery; P = 0.01).

30-day outcome in high risk, three-vessel disease, patients (EuroSCORE > or = 5).

Interestingly, pts with EF < 30 % were excluded!

No significant differences in the composite primary outcome (15 % vs. 17 %; P = 0.48) or the individual components were found at 30-day follow-up

341 pts randomly assign to either treatment.

Primary outcome was 30-day mortality and MACCE.

[12] Moller CH et al, Heart (2011)

3.5 years follow-up of the previous RCT.

All-cause mortality was significantly increased in the off-pump group (24 % vs. 15 %; HR 1.66, 95 % CI 1.02 to 2.73; p = 0.04), but cardiac-related death was not significantly different (10 % vs. 7 %; HR 1.30, 95 % CI 0.64 to 2.66; p = 0.47). I am wondering, if that reflects a sicker general population in the off-pump group!

Primary comparative outcome was intermediate mortality and MACCE.

[13] Houlind et al, J Thorac Cardiovasc Surg. (2014)

DOORS Trial.

The proportion of open left internal thoracic artery grafts was 95 % in both groups. However, vein graft patency after off-pump surgery was inferior to that after on-pump surgery.

Multicenter RCT. 900 patients randomized to On versus Off pump. 481 patients underwent angiography post operatively.

[14] Lamy A et al, American Heart Journal (2012)

CORONARY Trial

The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal MI within 1 and 5 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year and neuropsychological outcomes.

Multicenter RCT. 4752 patients randomized to On versus Off pump.

[15] Lamy A et al, N Engl J Med (2012)

CORONARY Trial.

No significant difference in the rate of the primary composite outcome. The authors concluded that although there was no significant difference between Off pump and on-pump CABG with respect to the 30-day mortality, MI, stroke, or renal failure requiring dialysis, the use of OPCAB resulted in reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney injury at the expense of an increased risk of early revascularization.

Early report of 30 days primary outcomes

[16] Lamy A et al, N Engl J Med (2013)

CORONARY Trial.

No difference in the rate of the primary composite outcome between off-pump and on-pump CABG

1 year results

[17] Diegeler A et al, N Engl J Med (2013)

GOPCABE Clinical Trial. 2539 patients above 75 years old, randomized to on versus off pump. The primary end point was a composite of death, stroke, myocardial infarction, repeat revascularization, or new renal-replacement therapy at 30 days and at 12 months after surgery.

There was no significant difference between the two groups, regarding the primary end points. Repeat revascularization occurred more frequently after off-pump CABG than after on-pump CABG (1.3 % vs. 0.4 %; odds ratio, 2.42; 95 % CI, 1.03 to 5.72; P = 0.04). points.

[18] Vieira de Melo RM et al, Eur J Cardiothorac Surg (2014)

5 year follow up of the MASS III TRIAL. Single Centre RCT that evaluates 308 patients: on-pump (153 pts) and off-pump (155pts).

The authors concluded that in patients with multivessel coronary artery disease, off-pump coronary artery bypass surgery resulted in a higher incidence of cardiac events at 5-year follow-up.

[19] Shroyer AL et al. Ann Thorac Surg (2014)

Diabetic subgroup of the ROOBY Trial. 835 patients: 402 pts received off-pump CABG and 433 pts received on-pump CABG.

The 1-year graft patency was lower and the short-term composite adverse outcome was higher on the off-pump CABG group.

[20] Cleveland JC et al, Ann Thorac Surg (2001)

STS Database.

Operative mortality 2.3 % for off-pump vs. 2.9 % with on-pump, P < 0.001.

From 1998 to 1999. 126 experience centres.

118140 CABGs with 11.717 Off-pump cases.

MACCE 10.62 % for off-pump vs. 14.15 % with on-pump, P < 0.001.

[21] Racz MJ et al, Journal Of American College Of Cardiology (2004)

CABG surgery from 1997 to 2000 in the state of New York.

Mortality was 2.02 % for off-pump vs. 2.16 % for on-pump (p = 0.390)

59044 on-pump pts vs. 9135 off-pump pts.

Off-pump patients had lower rates of perioperative stroke (1.6 % vs. 2.0 %, p = 0.003)

The study compare in-hospital mortality and complications and 3-year mortality.

On-pump patients experience better long-term survival and freedom from revascularization than off-pump patients. However, the survival benefit from on-pump procedures was no longer present in the last two years of the study.

[22] Mack M et al, J Thorac Cardiovasc Surg (2004)

4 centres over 3-year period: 7283 off-pump pts vs.10.118 on-pump.

Mortality was significantly less in the off-pump coronary artery bypass grafting group (2.8 % vs. 3.7 %, P < .001).

The study compare in-hospital mortality and complications.

Off-pump was associated with reductions in blood transfusion (32.6 % vs. 40.6 %, P < .001), stroke (1.4 % vs. 2.1 %, P = .002), renal failure (2.6 % vs. 5.2 %, P < .001), pulmonary complications (4.1 % vs. 9.5 %, P < .001), reoperation (1.7 % vs. 3.2 %, P < .001), atrial fibrillation (21.1 % vs. 24.99 %, P < .001).

[23] Hannan EL et al, Circulation (2007)

New York Database over 4 years period. 13889 off-pump vs. 35941 on-pump pts.

Off-pump had a significantly lower 30-day mortality rate (adjusted OR 0.81, 95 % confidence interval [CI] 0.68 to 0.97) and lower rates for 2 complications (stroke: adjusted OR 0.70, 95 % CI 0.57 to 0.86; respiratory failure: adjusted OR 0.80, 95 % CI 0.68 to 0.93).

What became important in this study was that

Off-pump patients had higher rates of subsequent revascularization (hazard ratio 1.55, 95 % CI 1.33 to 1.80). This could be potentially explained by the fact that Off-pump pts may have fewer grafts than originally planned.

Postoperative and 3 years outcomes compared between the two groups.

[24] Puskas J et al, 45^th STS Annual Meeting (2009)

STS database.

There was a significant reduction in operative mortality in the off-pump group, as well as a highly significant reduction in overall adverse cardiac events in this group.

65,864 underwent off-pump, whereas 120,594 underwent on-pump surgery.

[25] Wijeysundera DN et al, Journal Of American College Of Cardiology (2005)

A meta-analysis of 37 randomized controlled trials (RCTs) (n = 3,449) and 22 risk-adjusted (logistic regression or propensity-score) observational studies (n = 293,617).

In RCTs, Off-pump was associated with reduced atrial fibrillation (OR 0.59; 95 % CI 0.46 to 0.77) and trends toward reduced 30-day mortality (OR 0.91 95 % CI 0.45 to 1.83), stroke (OR 0.52; 95 % CI 0.25 to 1.05), and myocardial infarction (OR 0.79; 95 % CI 0.50 to 1.25).

Observational studies showed off-pump to be associated with reduced 30-day mortality (OR 0.72; 95 % CI 0.66 to 0.78), stroke (OR 0.62; 95 % CI 0.55 to 0.69), infarction (OR 0.66; 95 % CI 0.50 to 0.88), and atrial fibrillation (OR 0.78; 95 % CI 0.74 to 0.82).

At 2 years off-pump was associated with increase repeat revascularization procedures.

[26] Moller CH et al, Eur Heart Journal (2008)

Meta-analysis of 66 randomized trials published up till 2007.

Off-pump was associated with a significant reduced risk of atrial fibrillation (RR 0.69; 95 % CI 0.57-0.83).

[27] Moller CH et al

10 “low-bias” RCTs, 4950 pts.

30 % higher risk of all-cause mortality after off-pump CABG compared with on-pump CABG

[28] Feng ZZ et al, Ann Thorac Surg (2009)

Meta-analysis of ten randomized trials (2,018 patients) of Off-pump surgery versus on-pump.

There was no significant difference in 1-year mortality and MACCE between the 2 procedures.

Primary outcome was 1-year mortality and MACCE.

[29] Tagaki H et al, J Thorac Cardiovasc Surg (2010)

Meta-analysis of RCTs regarding graft patency after off-pump versus on-pump CABG.

The results of the meta-analysis favors on-pump.

The study concluded that off-pump surgery might increase graft occlusion by 32 %.

[30] Tagaki H et al Interact Cardiovasc Thorac Surg (2014)

A meta-analysis of RCTs for mid-term MACCE following off-pump versus on-pump coronary artery bypass grafting.

Similar mid term MACCE between the two groups.

[31] Attaran S et al, Perfusion (2014)

A meta-analysis of observational studies for Off-pump versus on-pump revascularization in females.

There was no statistical significant difference in mortality between the two groups, at 30 days.

23313 patients (n = 9596 Off pump, 13717 On pump).

[32] Chen YB et al, Chinese medical Journal (2012)

Forty-three randomized clinical trials were selected for meta-analysis with 8104 patients in the Off-pump group and 8724 cases in the On-pump group.

The meta-analyses suggest that Off-pump reduces the risk of postoperative AF compared with On-pump, but there is no significant difference in the incidences of stroke and MI between the two procedures.

[33] Godinho AS et al, Arquivos brasileiros de cardiologia. (2012)

Meta-analysis focused on nine randomized clinical trials, corresponding to a total of 75,086 patients.

A reduction of 18 % in the risk of cardiovascular mortality (OR: 0.82, 95%CI: 0.70 to 0.98, p = 0.03) and 27 % in the risk of stroke postoperatively (OR: 0.73, 95%CI: 0.63 to 0.85, p = 0.0001) were observed, both in favor of Off-Pump Surgery.

[34] Kuss O et al, J Thorac Cardiovasc Surg (2010)

A Meta-analysis of a total of 35 propensity score analyses was included in this study accounting for a total of 123,137 patients.

This study favors off-pump with lower mortality (odds ratio, 0.69; 95 % confidence interval, 0.60-0.75), stroke, renal failure, red blood cell transfusion (P < .0001), wound infection (P < .001), prolonged ventilation (P < .01), inotropic support (P = .02), and intraaortic balloon pump support (P = .05).

[35] Takagi H et al, Ann Thorac Surg (2010)

12 randomized trials (4,326 patients) of off-pump vs. on-pump CABG.

This study revealed a statistically significant increase in midterm all-cause mortality by a factor of 1.37 with off-pump relative to on-pump CABG (RR, 1.373; 95 % confidence interval, 1.043 to 1.808).

This report focused on late (> or = 1 year) all-cause mortality.

[36] Afilalo J et al, Eur Heart J (2012)

Meta analysis, Fifty-nine trials were included, encompassing 8961 patients

Similar 30-day mortality. However the incidence of post-operative stroke was reduced by 30 % on the off pump group.

[37] Sa MP et al, Rev Bras Cir Cardiovasc (2012)

Meta-analysis and meta-regression of 13,524 patients from randomized trials.

Similar 30-day mortality. However the incidence of post-operative stroke was reduced by 20.7 % on the off pump group.

6,758 off-pump pts and 6,766 on-pump CABG pts.

[38] Grover F, N Engl J Med (2012)

Editorial

An interesting editorial that “reconciles” the findings of the ROOBY and CORONARY trials

[39] Puskas J et al, Innovations (2005)

ISMICS recommendations

Identifies subgroup of patients that would potentially benefit from off pump techniques.

[40] ACCF/AHA practice Guidelines, Circulation (2011)

Guidelines

The guidelines contend, both approaches are reasonable, with certain factors tilting the balance one way or the other

[41] Yadava O et al, Indian Heart J (2013)

Real world experience, with 5000 cases of off pump

Very low conversion rate and low postoperative mortality.