Effect of Age on Clinical Outcomes Following On-/Off-Pump Coronary Artery Bypass: Meta-Analysis and Meta-Regression

Mauldon, Hayley; Dieberg, Gudrun; Smart, Neil; King, Nicola

doi:10.21470/1678-9741-2018-0388

REVIEW ARTICLE • Braz. J. Cardiovasc. Surg. 35 (5) • Sep-Oct 2020 • https://doi.org/10.21470/1678-9741-2018-0388 linkcopy

Effect of Age on Clinical Outcomes Following On-/Off-Pump Coronary Artery Bypass: Meta-Analysis and Meta-Regression

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objective: There is currently much debate about which patients would benefit more after on- or off-pump coronary artery bypass grafting (CABG). The aim of this meta-analysis and meta-regression is to investigate the effect of age on short-term clinical outcomes after these approaches.

Methods: To identify potential studies, systematic searches were carried out in the Excerpta Medica dataBASE (EMBASE), PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). The search strategy included the key concepts of “cardiopulmonary bypass” AND “coronary artery bypass grafting” AND “off pump” OR “on pump”. This was followed by a meta-analysis and meta-regression investigating the effect of age on the incidences of stroke, myocardial infarction (MI), and mortality.

Results: Thirty-seven studies including 15,324 participants were analysed. Overall, there was a significant odds reduction for patients receiving off-pump CABG suffering a stroke (odds ratio [OR] 0.770, 95% confidence intervals [CI] 0.594, 0.998, P=0.048); however, when patients were subdivided according to different age bands, this difference disappeared. There were also no significant differences in the odds of mortality (OR 0.876, 95% CI 0.703, 1.093, P=0.241) or MI (OR 0.937, 95% CI 0.795, 1.105, P=0.439). Meta-regression analysis revealed no significant relationship between age and stroke (P=0.652), age and mortality (P=548), and age and MI (P=0.464).

Conclusion: Patients undergoing CABG are becoming older and may suffer from multiple comorbidities increasing their risk profile. However, with respect to short-term clinical outcomes, the patient’s age does not help in determining whether off- or on-pump is superior.

Keywords:
Cardiopulmonary Bypass; Coronary Artery Bypass, Off-Pump; Myocardial Infarction Stroke; Comorbidity; Incidence

Abbreviations, acronyms & symbols
ARDS	= Acute respiratory distress syndrome	MDA	= Malondialdehyde
CABG	= Coronary artery bypass grafting	MI	= Myocardial infarction
CENTRAL	= Cochrane Central Register of Controlled Trials	MRI	= Magnetic resonance imaging
CI	= Confidence intervals	N/A	= Not available.
CK-MB	= Creatine kinase-muscle/brain	NR	= Not reported
CMA	= Comprehensive Meta-Analysis	NT-proBNP	= N-terminal pro b-type natriuretic peptide
CPB	= Cardiopulmonary bypass	OR	= Odds ratio
cTnI	= Cardiac troponin I	PRISMA	= Preferred Reporting Items for Systematic Reviews and Meta-analyses
EMBASE	= Excerpta Medica dataBASE	RCT	= Randomised controlled trials
GOPCABE	= German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients	UK	= United Kingdom
hs-CRP	= High-sensitivity creatine phosphate	USA	= United States of America
ICU	= Intensive care unit

Age range (years)	Study	N on CPB (off CPB)	Age on CPB (off CPB)	Male % on CPB (off CPB)	All outcome measures
51-55	Iqbal et al.^[²³^], 2014 Pakistan	100 (100)	53.5 ± 10 (51.6 ± 10.3)	NR	Encephalopathy Hospital stay ICU stay MI Mortality Renal failure Stroke Ventilation time
56-60	Bicer et al.^[²⁴^], 2014 Turkey	25 (25)	56.9 ± 10.7 (57.7 ± 8.4)	88 (88)	Mortality MDA hs-CRP M30 M65
	Gerola et al.^[²⁵^], 2004 Brazil	80 (80)	58.9 ± 8.9 (59.1 ± 9.7)	68 (64)	Atrial fibrillation CK-MB Hospital stay ICU stay MI Mortality Stroke
	Kobayashi et al.^[²⁶^] (JOCRI), 2005 Japan	86 (81)	59 ± 10 (60 ± 7)	86 (87)	Atrial fibrillation CK-MB Graft patency ICU stay MI Mortality Neuron specific enolase S-100 protein Stroke Ventilation time
	Penttila et al.^[²⁷^], 2001 Finland	11 (11)	59.2 59.5	NR	MI Myocardial markers Myocardial metabolism
61-65	Al-Ruzzeh et al.^[²⁸^], 2006 UK	84 (84)	63.1 ± 9.6 (63.1 ± 11)	84 (83)	Atrial fibrillation Blood transfusions Graft patency Health-related quality of life Hospital stay ICU stay Mortality Neurocognitive function Stroke Ventilation time
	Angelini et al.^[²⁹^], 2002 UK	BHACAS 1 100 (100) BHACAS 2 101 (100)	BHACAS 1 61.7 ± 8.6 (62.2 ± 9.6) BHACAS 2 61.2 ± 9.2 (63.8 ± 8.5)	BHACAS 1 79 (82) BHACAS 2 85 (82)	Atrial fibrillation MI Mortality Stroke
	Ascione et al.^[³⁰^], 2000 UK	100 (100)	63 (63)	79 (82)	Atrial fibrillation Hospital stay ICU stay MI Mortality Stroke Ventilation time
	Fattouch et al.^[³¹^], 2009 Italy	65 (63)	61 ± 18 (63 ± 16)	77 (61)	cTnI Cardiac contractile function Hospital stay ICU stay Mortality Ventilation time
	Jongman et al.^[³²^], 2014 The Netherlands	29 (30)	63 (63)	90 (90)	Cardiac failure Inflammatory markers Major bleeding Pulmonary embolism Renal failure Stroke
	Khan et al.^[³³^], 2004 UK	50 (54)	64.7	82 (93)	Blood loss Extubation time Hospital stay ICU stay Infection Low cardiac output MI Mortality Repeat surgery
	Kok et al.^[³⁴^], 2014 The Netherlands	29 (30)	62.6 ± 9.9 (63 ± 9)	90 (90)	Cerebral oxygenation Cognitive dysfunction Hospital stay ICU stay Stroke
	Légaré et al.^[³⁵^], 2004 Canada	150 (150)	63.7 ± 10 (62.1 ± 10.1)	79 (81)	Atrial fibrillation Hospital stay ICU stay MI Mortality Stroke Transfusion requirement Ventilation time Wound infection
	Lingaas et al.^[³⁶^], 2004 Norway	60 (60)	65 ± 8.3 64 ± 7.8	72 (85)	CPB time Ventilation time Reintubation Bleeding Blood transfusions Atrial fibrillation CK-MB Aspartate aminotransferase Stroke Mortality Mediastinitis Graft patency
	Lund et al.^[³⁷^], 2003 Norway	22 (29)	64 (62)	73.9 (89.7)	Cerebral blood flow Cerebral MRI Neuropsychologic tests Stroke
	Michaux et al.^[³⁸^], 2011 Switzerland	25 (25)	65 ± 8 (61 ± 9)	84 (84)	Atrial fibrillation cTnI Hospital stay ICU stay MI Mortality Right ventricular function Ventilation time >12 hours
	Motallebzdah et al.^[³⁹^], 2004 UK	20 (15)	63 (65)	90 (93)	Cerebral blood flow S100 protein Stroke
	Motallebzdah et al.^[⁴⁰^], 2007 UK	104 (108)	65.1 ± 0.9 (63.9 ± 0.9)	91 (87)	Cerebral emboli Mortality Neurocognitive function Stroke
	Nathoe et al.^[⁴¹^] (Octopus), 2003 USA	139 (142)	60.8 ± 8.8 61.7 ± 9.2	71 (66)	Cost MI Mortality Quality of life Repeat revascularisation Stroke
	Puskas et al.^[⁴²^] (SMART), 2003 USA	99 (98)	62.5 ± 9.5 (62.2 ± 11.1)	77 (78)	Atrial fibrillation Coagulopathy and transfusion Hospital stay ICU stay MI Mortality Stroke
	Rastan et al.^[⁴³^], 2005 Germany	20 (20)	65.3 ± 3.9 (63 ± 6)	80 (80)	CK-MB C-reactive protein cTnI Intraoperative myocardial ischaemia MI Mortality NT-proBNP Oxidative stress Stroke
	Sahlman et al.^[⁴⁴^], 2003 Finland	26 (24)	61.5 ± 8.1 (64 ± 9)	77 (88)	Extubation time Bleeding CK-MB ICU stay Hospital stay Weight gain Complement C3 C4 Protein carbonyls Wound infection Low cardiac output syndrome Cerebral infarction Oxidative stress markers
	Shroyer et al.^[⁴⁵^] (ROOBY), 2009 USA	1099 (1104)	62.5 ± 8.5 (63 ± 8.5)	99 (99)	Cardiac arrest Coma Hospital stay ICU stay Mediastinitis Mortality New mechanical support Renal failure Reoperation Stroke Tracheostomy Ventilation time
	Straka et al. ^[⁴⁶^] (PRAGUE-4), 2004 Czech Republic	184 (204)	62 (63)	86 (77)	Atrial fibrillation Hospital stay ICU stay MI Mortality Renal failure Stroke Ventilation time
	Vedin et al.^[⁴⁷^], 2006 ^[⁴⁷^] Sweden	37 (33)	65 (65)	84 (78)	Anxiety Cognitive function Depression MI Stroke
66-70	Carrier et al.^[⁴⁸^], 2003 Canada	37 (28)	70 ± 6 (70 ± 8)	84 (68)	Mortality MI Stroke Renal insufficiency Respiratory failure/infection Bleeding Blood transfusions ICU stay Hospital stay
	Lamy et al ^[⁴⁹^] (CORONARY), 2012 Canada	2377 (2375)	67.5 ± 6.9 (67.6 ± 6.7)	82 (80)	Atrial fibrillation MI Mortality New renal failure Stroke
	Lee et al ^[⁵⁰^], 2003Hawaii	30 (30)	66 ± 11.2 (65.5 ± 9.6)	73 (80)	Cerebral microemboli Cerebral perfusion Cost Hospital stay Mortality Neurological function Stroke
	Muneretto et al.^[⁵¹^], 2003 Italy	88 (88)	66 ± 9 (67 ± 8)	59 (63)	Abdominal infarction Atrial fibrillation Hospital stay ICU stay MI Mortality Stroke Ventilation time
	Nesher et al.^[⁵²^], 2006 Israel	60 (60)	68 ± 5 (67 ± 1)	77 (73)	CK-MB cTnI Cytokines Hospital stay Stroke Ventilation time
	Niranjan et al.^[⁵³^], 2006 UK	40 (40)			Atrial fibrillation Blood transfusion requirements Clotting tests Hospital stay ICU stay Mortality Postoperative blood loss Stroke Ventilation time
71-75	Hlavicka et al.^[⁵⁴^] (PRAGUE-6), 2016 Czech Republic	108 (98)	73.6 ± 7.4 74.7 ± 6.5	57.4 (59.2)	MI Mortality Renal failure Stroke
	Houlind et al.^[⁵⁵^] (DOORS), 2012 Denmark	450 (450)	75 (75)	78 (76)	Hospital stay ICU stay MI Mortality Quality of life Stroke
	Lemma et al.^[⁵⁶^] (ON-OFF), 2012 Italy	203 (208)	73 (74)	69 (70)	MI Mortality Renal failure Stroke Reoperation for bleeding ARDS
76-80	Diegeler et al. ^[¹⁰^] (GOPCABE), 2013 Germany	1207 (1187)	78.4 ± 2.9 (78.6 ± 3.0)	68 (69)	Hospital stay ICU stay MI Mortality New renal-replacement therapy Repeat revascularisation Stroke Ventilation time
	Møller et al. ^[⁵⁷^] (BBS), 2010 Denmark	163 (176)	75.6 ± 4.9 (76.1 ± 5.2)	64 (65)	Cardiac arrest with successful resuscitation Coronary reintervention Low cardiac output syndrome MI Mortality Stroke
	Rogers et al.^[⁵⁸^] (CRISP), 2014 UK	53 (53)	75.7 ± 7.7 (76.4 ± 5.8)	76 (78)	MI Mortality Prolonged initial ventilation Renal failure Sternal wound dehiscence Stroke

Authors' roles & responsibilities
HM	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published.
GD	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published.
NS	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published.
NK	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published.

Study	Reason
Chowdhury et al., 2008	Mean age crossed over two age groups
Covino et al., 2001	Did not record mean age
Formica et al., 2013	Mean age crossed over two age groups
Gulielmos et al., 2000	Mean age crossed over two age groups
Hernandez et al., 2007	Did not record mean age
Hoel et al., 2007	Did not record mean age
Kobayashi et al., 2005	Mean age crossed over two age groups
Kochamba et al., 2000	Mean age crossed over two age groups
Kunes et al., 2007	Mean age crossed over two age groups
Medved et al., 2008	Mean age crossed over two age groups
Paparella et al., 2006	Did not record mean age
Rachwalik et al., 2006	Mean age crossed over two age groups
Rainio et al., 2007	Mean age crossed over two age groups
Raja et al., 2003	Did not record mean age

Study	Randomisation	Methods of randomisation	Methods of blinding described	Method of blinding appropriate	Withdrawals/dropouts described	Other potential bias	Score (out of 6)
Al-Ruzzeh et al.^[²⁸^], 2006	Yes	Yes	No	N/A	No	No	3
Angelini et al.^[²⁹^], 2002	Yes	Yes	No	N/A	No	Yes	2
Ascione et al.^[³⁰^], 2000	Yes	Yes	No	N/A	No	No	3
Bicer et al.^[²⁴^], 2014	Yes	No	No	N/A	No	No	2
Carrier et al.^[⁴⁸^], 2003	Yes	No	No	N/A	No	No	2
Diegeler et al.^[¹⁰^], 2013	Yes	Yes	No	N/A	Yes	No	4
Fattouch et al.^[³¹^], 2009	Yes	Yes	No	N/A	No	No	3
Gerola et al.^[²⁵^], 2004	Yes	No	No	N/A	No	No	2
Hlavicka et al.^[⁵⁴^], 2013	Yes	Yes	No	N/A	Yes	No	4
Houlind et al. ^[²²^], 2012	Yes	Yes	No	N/A	Yes	No	4
Iqbal et al.^[²³^], 2014	Yes	No	No	N/A	No	No	2
Jongman et al.^[³²^], 2014	Yes	No	No	N/A	No	No	2
Khan et al.^[³³^], 2004	Yes	No	No	N/A	No	No	2
Kobayashi et al.^[²⁶^], 2005	Yes	Yes	No	N/A	No	No	3
Kok et al.^[³⁴^], 2014	Yes	No	No	N/A	Yes	No	3
Lamy et al.^[⁴⁹^], 2012	Yes	Yes	No	N/A	No	No	3
Lee et al.^[⁵⁰^], 2003	Yes	Yes	No	N/A	No	No	3
Légaré et al.^[³⁵^], 2004	Yes	Yes	No	N/A	No	Yes	2
Lemma et al.^[⁵⁶^], 2012	Yes	Yes	No	N/A	Yes	No	4
Lingaas et al.^[³⁶^], 2004	Yes	No	No	N/A	No	No	2
Lund et al.^[³⁷^], 2003	Yes	No	No	N/A	Yes	No	3
Michaux et al.^[³⁸^], 2011	Yes	Yes	No	N/A	No	Yes	2
Moller et al.^[⁵⁷^], 2010	Yes	Yes	No	N/A	No	Yes	2
Motallebzadeh et al.^[³⁹^], 2004	Yes	Yes	No	N/A	No	No	3
Motallebzadeh et al.^[⁴⁰^], 2007	Yes	Yes	No	N/A	No	No	3
Munereto et al.^[⁵¹^], 2003	Yes	No	No	N/A	No	No	2
Nathoe et al.^[⁴¹^], 2003	Yes	Yes	No	N/A	No	No	3
Nesher et al.^[⁵²^], 2006	Yes	Yes	No	N/A	Yes	No	4
Niranjan et al.^[⁵³^], 2006	Yes	Yes	No	N/A	No	No	3
Penttila et al.^[²⁷^], 2001	Yes	No	No	N/A	No	No	2
Puskas et al.^[⁴²^], 2003	Yes	Yes	No	N/A	Yes	Yes	3
Rastan et al.^[⁴³^], 2005	Yes	Yes	No	N/A	No	No	3
Rogers et al.^[⁵⁸^], 2014	Yes	Yes	No	N/A	Yes	Yes	3
Sahlman et al.^[⁴⁴^], 2003	Yes	No	No	N/A	No	No	2
Shroyer et al.^[⁴⁵^], 2009	Yes	Yes	No	N/A	Yes	Yes	3
Straka et al.^[⁴⁶^], 2004	Yes	Yes	No	N/A	Yes	No	4
Vedin et al.^[⁴⁷^], 2006	Yes	No	No	N/A	Yes	No	3

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[TFN1] ARDS=acute respiratory distress syndrome; CK-MB=creatine kinase-muscle/brain; CPB=cardiopulmonary bypass; cTnI=cardiac troponin I; hs-CRP=high-sensitivity creatine phosphate; ICU=intensive care unit; MDA=malondialdehyde; MI=myocardial infarction; MRI=magnetic resonance imaging; NR=not reported; NT-proBNP=N-terminal pro b-type natriuretic peptide; UK=United Kingdom; USA=United States of America