Off‐Pump Coronary Artery Bypass Grafting: 30 Years of Debate
2018; Wiley; Volume: 7; Issue: 16 Linguagem: Inglês
10.1161/jaha.118.009934
ISSN2047-9980
AutoresMario Gaudino, Gianni D. Angelini, Charalambos Antoniades, Faisal G. Bakaeen, Umberto Benedetto, Antonio M. Calafiore, Antonino Di Franco, Michele Di Mauro, Stephen E. Fremes, Leonard N. Girardi, David Glineur, Juan B. Grau, Guo‐Wei He, Carlo Patrono, John D. Puskas, Marc Ruel, Thomas A. Schwann, Derrick Y. Tam, James Tatoulis, Robert F. Tranbaugh, Michael P. Vallely, Marco A. Zenati, Michael J. Mack, David P. Taggart,
Tópico(s)Coronary Interventions and Diagnostics
ResumoHomeJournal of the American Heart AssociationVol. 7, No. 16Off‐Pump Coronary Artery Bypass Grafting: 30 Years of Debate Open AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessReview ArticlePDF/EPUBOff‐Pump Coronary Artery Bypass Grafting: 30 Years of Debate Mario Gaudino, MD, Gianni D. Angelini, MD, Charalambos Antoniades, MD, Faisal Bakaeen, MD, Umberto Benedetto, PhD, Antonio M. Calafiore, MD, Antonino Di Franco, MD, Michele Di Mauro, MD, Stephen E. Fremes, MD, Leonard N. Girardi, MD, David Glineur, MD, Juan Grau, MD, Guo‐Wei He, MD, Carlo Patrono, MD, John D. Puskas, MD, Marc Ruel, MD, MPH, Thomas A. Schwann, MD, Derrick Y. Tam, MD, James Tatoulis, MD, Robert Tranbaugh, MD, Michael Vallely, MD, Marco A. Zenati, MD, Michael Mack, MD, David P. Taggart, MD and Arterial Grafting International Consortium (ATLANTIC) Alliance Mario GaudinoMario Gaudino Department of Cardio‐Thoracic Surgery, Weill Cornell Medicine, New York City, NY , Gianni D. AngeliniGianni D. Angelini Bristol Heart Institute, University of Bristol, United Kingdom , Charalambos AntoniadesCharalambos Antoniades University of Oxford, United Kingdom , Faisal BakaeenFaisal Bakaeen Cleveland Clinic, Cleveland, OH , Umberto BenedettoUmberto Benedetto Bristol Heart Institute, University of Bristol, United Kingdom , Antonio M. CalafioreAntonio M. Calafiore Cardiac Surgery, Pope John Paul II Foundation, Campobasso, Italy , Antonino Di FrancoAntonino Di Franco Department of Cardio‐Thoracic Surgery, Weill Cornell Medicine, New York City, NY , Michele Di MauroMichele Di Mauro Cardiovascular Disease Institute, University of L'Aquila, Italy , Stephen E. FremesStephen E. Fremes Schulich Heart Centre, Sunnybrook Health Science, University of Toronto, Canada , Leonard N. GirardiLeonard N. Girardi Department of Cardio‐Thoracic Surgery, Weill Cornell Medicine, New York City, NY , David GlineurDavid Glineur Division of Cardiac Surgery, Ottawa Heart Institute, Ottawa, Canada , Juan GrauJuan Grau Division of Cardiac Surgery, Ottawa Heart Institute, Ottawa, Canada , Guo‐Wei HeGuo‐Wei He TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China , Carlo PatronoCarlo Patrono Department of Pharmacology, Catholic University School of Medicine, Rome, Italy , John D. PuskasJohn D. Puskas Department of Cardiovascular Surgery, Icahn School of Medicine at Mount Sinai, New York City, NY , Marc RuelMarc Ruel University of Ottawa Heart Institute, Ottawa, Canada , Thomas A. SchwannThomas A. Schwann University of Toledo College of Medicine, Toledo, OH , Derrick Y. TamDerrick Y. Tam Schulich Heart Centre, Sunnybrook Health Science, University of Toronto, Canada , James TatoulisJames Tatoulis Department of Surgery, University of Melbourne, Parkville, Australia , Robert TranbaughRobert Tranbaugh Department of Cardio‐Thoracic Surgery, Weill Cornell Medicine, New York City, NY , Michael VallelyMichael Vallely Sydney Medical School, The University of Sydney, Australia , Marco A. ZenatiMarco A. Zenati Harvard Medical School, Boston, MA , Michael MackMichael Mack The Heart Hospital Baylor Plano, Plano, TX , David P. TaggartDavid P. Taggart University of Oxford, United Kingdom and Arterial Grafting International Consortium (ATLANTIC) Alliance Originally published14 Aug 2018https://doi.org/10.1161/JAHA.118.009934Journal of the American Heart Association. 2018;7:e009934IntroductionOff‐pump coronary artery bypass surgery (OPCAB) has been performed for >30 years.The promotion of OPCAB was based on its potential benefits over some of the limitations of traditional on‐pump coronary artery bypass surgery (ONCAB) by avoiding the trauma of cardiopulmonary bypass (CPB) and by minimizing aortic manipulation. As such, reductions in early mortality and perioperative neurological events, renal failure, blood product transfusions, and hospital length of stay were expected according to the OPCAB proponents. In contrast, critics of OPCAB remain concerned about incomplete and/or poorer quality coronary revascularization with a potential increase in the need for repeat revascularization and late mortality.Despite 3 decades of debate, 115 randomized trials, and >60 meta‐analyses comparing on‐ and off‐pump coronary artery bypass grafting (CABG), controversy on both the role of and indications for OPCAB remains vigorous.In this review, we provide a comprehensive update of the evidence for the differences in the biological effects of off‐ and on‐pump surgery and the comparison of the clinical and angiographic results of the 2 techniques. Furthermore, we critically address the relevant technical aspects of OPCAB, the importance of surgeon experience, and the difference in the costs for the 2 procedures.Search StrategyThe Arterial Grafting International Consortium (ATLANTIC) Alliance is an international writing group on coronary surgery. In January 2018, a comprehensive search to identify studies that evaluated the biological, clinical, angiographic, and economic aspects of OPCAB was performed in the following databases from inception to present: Ovid Medline, Ovid Embase, and the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials [CENTRAL], Cochrane Methodology Register). Search keywords included myocardial revascularization in combination with coronary artery bypass, on pump, off pump, and OPCAB. Relevant abstracts were reviewed, and the related articles function was used for all included studies. References for all selected studies were cross‐checked. The writing group selected the most relevant papers according to both methodological and clinical considerations. Observational series were considered only in the absence of data from randomized controlled trials (RCTs).The Technical Evolution of Beating‐Heart Coronary Artery Bypass SurgeryThe very first direct coronary revascularization procedures in the early 1960s were performed on the beating heart without CPB.1 However, the technique was soon abandoned because of developments in extracorporeal circulation and improvement in myocardial protection that made the surgery safer, standardized, and reproducible. In the early 1980s, 2 South American surgeons, Buffolo2 and Benetti,3 published their extensive series of OPCAB. Most patients received grafts to the left anterior descending coronary artery (LAD) and the main right coronary artery, but with more limited and difficult grafting of coronary arteries on the posterior and lateral wall. In the mid 1990s, a minimally invasive left internal mammary artery (LIMA)–LAD performed through a small left anterior thoracotomy on the beating heart4 was proposed in combination with percutaneous coronary intervention (PCI) for the non‐LAD targets.5Innovative technology played a key role in the development of OPCAB by minimizing the motion of the heart during construction of the anastomosis. Initially, stabilization of the target coronary vessel was obtained by stay sutures, but the advent of mechanical stabilizers, by means of pressure or suction pods, transformed the way OPCAB was performed, accompanied by an evident improvement in surgical results.6 The critical challenge was the exposure of the lateral and inferior walls. Initially, lifting of the heart and exposure of the targets were achieved with multiple slings7 or pericardial stitches, as proposed by Lima and Salerno.8 The commercialization of pressure‐ and vacuum‐assisted positioners further changed the field and allowed minimization of hemodynamic changes during exposure. The use of intracoronary shunts rather than snaring of the target native coronary vessel has been shown to significantly reduce intraoperative myocardial dysfunction and hemodynamic instability during OPCAB.9The use of a transit‐time flowmeter, high‐resolution epicardial ultrasound, or intraoperative fluorescence imaging allowed intraoperative control of the quality of the anastomosis, an issue of particular relevance during the technically more complex OPCAB procedure.10For the future of OPCAB, technology will play an increasingly important role with the adoption of hybrid revascularization and robotic assisted OPCAB. The concept of hybrid coronary revascularization (HCR) stems from the hypothesis that the LIMA‐LAD graft is superior to coronary stenting of the LAD, whereas contemporary drug‐eluting stent–PCI is noninferior to venous bypass grafts used for non‐LAD targets. Although still limited to sporadic experiences in dedicated centers, HCR has the potential to combine the advantages of minimally invasive OPCAB with complete coronary revascularization.The use of robotic assistance during CABG has been associated with superior cosmetic results and reduced postoperative pain but also longer operative times and higher costs.11Differences in Systemic Inflammatory Reaction and Platelet/Coagulation Activation After On‐ and Off‐Pump CABGCABG elicits a complex prothrombotic and proinflammatory response that peaks within a time frame spanning from the end of CPB to the early hours thereafter. These molecular changes may persist for days or weeks after CABG.12 In particular, several studies have described marked and protracted activation of several molecular pathways, reflecting a systemic inflammatory reaction, platelet and coagulation activation, and increased oxidative stress and endothelial dysfunction.13 Interestingly, these changes appear to occur after both ONCAB and OPCAB, with a relatively limited number of these pathways (eg, oxidant stress) showing more pronounced activation in the presence of CPB.13Systemic Inflammatory ReactionPatients undergoing CABG constitute a distinct high‐risk group characterized by advanced atherosclerotic disease, low‐grade systemic inflammation, and the clustering of several other comorbidities.13 The CABG operation per se is a potent triggering factor for cardiovascular events because it elicits major endocrine stress and systemic inflammatory response, which involves the release of acute‐phase proteins and sepsis‐like symptoms during postoperative recovery.14 The inflammatory response during CABG may be related, at least in part, to the use of CPB that induces leukocyte and platelet activation, thrombin and plasmin‐mediated procoagulant and fibrinolytic effects, and a rapid and sustained multifold increase in the circulating levels of proinflammatory mediators.16 Myocardial tissue ischemia as a result of aortic cross‐clamp, reperfusion injury, plaque rupture and microembolization, and other factors (eg, type of anesthesia) also may play a role in CABG‐related inflammation.17If and to what extent avoidance of CPB can reduce or even eliminate the systemic inflammatory reaction after surgery is controversial. Studies that evaluated the circulating levels of proinflammatory cytokines (IL‐6, ‐8, and ‐10) after off‐ and on‐pump‐ surgery reported contradictory results.14The concomitant use of cardiotomy suction or non–heparin‐bounded CPB circuits in some of the trials is a plausible cause of heterogeneity and may partially explain the contradictory results.Interestingly, the severity of the inflammatory response to OPCAB might be affected by the type of anesthesia.23 Inflammation has been proposed to have an important role in determining early postoperative complications (eg, low‐output syndrome, myocardial injury, and atrial fibrillation or stroke). Indeed, increased preoperative CRP (C‐reactive protein) levels are independently associated with early and late mortality in CABG patients.24 In other studies, preoperative levels of IL‐6, IL‐8, and MCP‐1 (monocyte chemoattractant protein 1) predict postoperative atrial fibrillation development in CABG patients.25 Gaudino et al26 described a significant correlation between a single‐base promoter mutation of the polymorphism of the IL6 gene, the postoperative level of IL‐6, and the development of pulmonary and renal complications and atrial fibrillation after CABG. In RCTs, OPCAB has been associated with significantly lower myocardial injury and increase in inflammatory mediators compared with ONCAB,14 although early mortality rates did not differ significantly.27 Nevertheless, it must be noted that the results of pharmacological treatment aimed at reducing the postoperative inflammatory reaction after CABG (corticosteroids, statins) have been mixed,28 so the role of attempts to modulate inflammation in determining postoperative clinical outcome after CABG remains to be determined.Platelet and Coagulation ActivationActivation of the plasmatic and cellular components of the hemostatic system occurs through 2 distinct mechanisms, namely, contact of blood with the surgical wound and contact of blood with the foreign surface of the CPB circuit.30 The former plays a major role in the early activation of the hemostatic system that results in thrombin generation. Besides catalyzing the conversion of fibrinogen to fibrin, thrombin has multiple cellular targets (both in blood [eg, platelets] and the vessel wall) through the interaction with protease‐activated receptors.30 Moreover, there is bidirectional interplay between blood coagulation and inflammation, with activation of the former leading to an inflammatory reaction and vice versa.30 Circulating platelets are activated during CABG by several distinct mechanisms, including thrombin interacting with platelet PAR‐1 (protease‐activated receptor 1), interaction with fibrinogen bound to the CPB circuit, and contact with foreign surfaces. These activation processes eventually lead to reduced numbers of circulating platelets and perioperative platelet dysfunction.30 Moreover, activated platelets release a broad range of inflammatory mediators, thereby reinforcing the inflammatory reaction.31 The increased vascular biosynthesis of the antithrombotic prostanoid prostacyclin (PGI2) represents a homeostatic response to inflammation and platelet activation.32A limited number of studies have compared the effects of ONCAB versus OPCAB on platelet activation and aggregation and failed to demonstrate major differences between them.30 It should be emphasized that these studies relied on measurements of platelet function ex vivo, which do not necessarily reflect the extent of platelet activation in vivo.31A different and more clinically relevant way of assessing the potential hemostatic/prothrombotic differences related to ONCAB versus OPCAB is represented by studies of the pharmacodynamic response to antiplatelet drugs in these settings.32 In a study by Zimmermann et al,33 the antiplatelet effect of aspirin (100 mg/day started on day 1 after surgery) evaluated at day 5 was largely impaired after CPB but not after CABG without CPB; therefore, increased platelet turnover after CPB appears to contribute to transient aspirin "resistance" because an increased number of new platelets might be competent to form Thromboxane A2 (TXA2) within the 24‐hour dosing interval.33 Consistent with this hypothesis, Cavalca et al recently reported impaired aspirin pharmacodynamics early after ONCAB that were associated with significant increases in immature platelets, total platelets, platelet mass, thrombopoieitin, IL‐6, glycocalicin, leukocytes, and high‐sensitivity CRP.32 IL‐6 can control inflammation through CRP and modulate megakaryocyte fragmentation, differentiation, and platelet release directly or through thrombopoieitin.32 Changes in thrombopoietic indexes were largely reversible 3 months after surgery.32 As shown by 3 independent studies, shortening the dosing interval (ie, twice‐daily dosing), but not doubling the dose, safely rescued the impaired antiplatelet effect of low‐dose aspirin and prevented platelet activation associated with acute inflammation and enhanced platelet turnover following cardiac surgery.32To summarize, at present there is no clear‐cut demonstration of a substantial reduction of the postoperative systemic inflammatory reaction and platelet activation after OPCAB. The antiplatelet effect of low‐dose aspirin is transiently impaired following ONCAB because of enhanced platelet turnover.Comparison of Short‐Term Clinical Outcomes of On‐ and Off‐Pump CABGThe benefits and risks of OPCAB have been the subject of several large RCTs, observational studies and registries, and >60 meta‐analyses. In the largest randomized comparisons (CORONARY [CABG Off or On Pump Revascularization] and ROOBY [Randomized On/Off Bypass] trials), there were no differences in the primary study end point at 30 days.27 In CORONARY,27 the primary composite outcome of death, nonfatal stroke, or nonfatal myocardial infarction (MI) was similar between OPCAB and ONCAB (9.8% versus 10.3%, P=0.59). Similarly in ROOBY, the primary composite outcome of 30‐day death or major complications was similar between the 2 arms (7.0% versus 5.6%, P=0.19).38 Furthermore, there was no difference in any individual component of these early composite outcomes (Table 1). Consistent with the purported benefits of off‐pump surgery, several other perioperative complications (transfusion, reoperation for bleeding, acute kidney injury, and respiratory complications) were reduced in the off‐pump patients in CORONARY.Table 1 Early and Late Outcomes of ONCAB Versus OPCABTrialMedian Follow‐upInterventionsEarly OutcomesLate OutcomesMACCE DefinitionMortalityRRStrokeMIMortalityStrokeMIRRMACCECORONARY394.8 yONCAB59/2377 (2.5)4/2328 (0.2)27/2377 (1.1)170/2377 (7.2)322/2377 (13.5)66/2377 (2.8)194/2377 (8.2)55/2377 (2.3)560/2377 (23.6)Death from any cause, nonfatal MI, nonfatal stroke, new renal failure requiring dialysis, RROPCAB60/2375 (2.5)16/2330 (0.7)24/2375 (1.0)158/2375 (6.7)346/2375 (14.6)55/2375 (2.3)178/2375 (7.5)66/2375 (2.8)548/2375 (23.1)ROOBY405 yONCAB13/1099 (1.2)8/1099 (0.7)8/1099 (0.7)17/1099 (1.8)131/1099 (11.9)···105/1099 (9.6)131/1099 (11.9)131/1099 (11.9)Death from any cause, acute MI, RROPCAB18/1104 (1.6)8/1104 (0.7)14/1104 (1.3)15/1104 (1.7)168/1104 (15.2)···134/1104 (12.1)145/1104 (13.1)145/1104 (13.1)GOPCABE411 yONCAB34/1207 (2.8)5/1207 (0.4)32/1207 (2.7)20/1207 (1.7)95/1191 (8)52/1191 (4.4)28/1191 (2.4)24/1191 (2.0)167/1191 (14)Death from any cause, MI, stroke, RR, new renal failure requiring dialysisOPCAB31/1187 (2.6)15/1187 (1.3)26/1187 (2.2)18/1187 (1.5)83/1179 (7)41/1179 (3.5)25/1179 (2.1)36/1179 (3.1)154/1179 (13.1)Data are shown as frequency (percentage). CABG indicates coronary artery bypass grafting; CORONARY, CABG Off‐ or On‐Pump Revascularization; GOPCABE, German Off‐Pump Coronary Artery Bypass Grafting in Elderly Patients; MACCE, major adverse cardiovascular or cerebral events; MI, myocardial infarction; ONCAB, on‐pump coronary artery bypass surgery; OPCAB, off‐pump coronary artery bypass surgery; ROOBY, Randomized On/Off Bypass; RR, repeated revascularization.In GOPCABE (German Off‐Pump CABG in Elderly Trial), a German RCT including only patients aged >75 years, there was no significant difference in the primary composite end point of death, stroke, MI, or new renal replacement therapy (7.8% versus 8.2%, P=0.74) at 30 days41 and no differences in the individual components of the composite end point (Table 1). However, there was an increased number of repeat revascularizations with OPCAB (1.3% versus 0.4%, P=0.04), a finding also observed in CORONARY (0.7% versus 0.2%, P=0.01).Of note, no reduction in stroke was noted both in hospital and at 1 year (CORONARY: 1.5% versus 1.7%; [hazard ratio (HR): 0.90; 95% confidence interval (CI), 0.57–1.41]; GOPCABE: 3.5% versus 4.4%; P=0.26).41At 12 months, the primary composite end point was not different in the OPCAB and ONCAB patients in GOPCABE (13.1% versus 14.0%; P=0.48) or in CORONARY (12.1% versus 13.3%; P=0.24). In ROOBY, the primary outcome favored on‐pump surgery (9.9% versus 7.4%; P=0.04), as did death from cardiac causes (2.7% versus 1.3%; P=0.03).In contrast to the randomized trials, large propensity‐matched databases have reported superior short‐term outcomes with OPCAB, particularly in higher risk patients.Polomsky and associates, using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD) on 876 081 elective isolated CABG operations, found that the odds ratios (ORs) for death and most major complications were significantly lower with OPCAB than with ONCAB.43A meta‐analysis of 35 propensity‐matched studies and 123 137 patients found OPCAB to be superior to on‐pump surgery for all short‐term outcomes including mortality.44To summarize, RCTs have reported similar operative risk for off‐ and on‐pump CABG, whereas single‐center studies have reported better outcomes, particularly in high‐risk patients.Comparison of Long‐Term Clinical Outcomes of On‐ and Off‐Pump CABGConflicting evidence exists on whether off‐pump CABG is associated with inferior long‐term outcomes. At 5 years, there was no difference in the primary outcome in the CORONARY trial.39 In the ROOBY trial, however, 5‐year survival was significantly worse in the off‐pump group (15.2% versus 11.9%; P=0.02).40 Event‐free survival was also significantly decreased in the off‐pump group (31.0% versus 27.1%; P=0.05), along with MI and the need for repeat revascularization (Table 1).In a single‐center observational study of 12 812 patients from Emory University, Atlanta, GA, USA, there was no difference in 10‐year mortality between on‐ and off‐pump surgery after propensity score covariate adjustment (HR: 1.00; 95% CI, 0.88–1.14).45 Importantly, the authors reported that the key to long‐term survival was completeness of revascularization in both on‐ and off‐pump patients. Similarly, in 942 propensity score–matched patient pairs from a single Italian center, there was no difference in 10‐year mortality between on‐ and off‐pump surgery (HR: 1.3; 95% CI, 0.91–1.9).46 In a study from the United Kingdom of >13 000 propensity‐matched patients followed for 13 years, there was no difference in survival, suggesting that when OPCAB is performed by highly experienced surgeons, there is no adverse effect on survival.47In contrast, a propensity‐matched single‐institution study from Baylor Research Institute, Dallas, TX, USA showed an elevated risk of late mortality at 10 years with OPCAB (HR: 1.18; 95% CI, 1.02–1.38).48 These concerns about late mortality were further explored in a meta‐analysis of 42 RCTs and 31 risk‐adjusted observational studies that included 1.2 million patients.49 OPCAB was associated with a statistically significant 10% relative increase in the probability of mortality at 5 years (95% CI, 5.0–15.0%) that increased to 14% at 10 years in the observational studies (95% CI, 11.0–17.0%). It is important to note, however, that although statistical significance was reached, the clinical relevance of the reported difference remains to be determined (absolute difference: 0.5% at 5 years and 3% at 10 years).The most recent meta‐analysis including only RCTs with ≥4‐year outcome and pooling data from 8145 participants reported an OR for long‐term mortality of 1.16 for OPCAB (95% CI, 1.02–1.32).50To conclude, long‐term data are discordant. Based on the current evidence, the possibility that off‐pump surgery results in worse clinical outcomes cannot be excluded.OPCAB in Specific Subsets of PatientsHigh‐Risk PopulationsMultiple studies have suggested a benefit of OPCAB in high‐risk patient populations. A recent meta‐analysis of RCTs demonstrated a significant relationship between the patient risk profile and the benefits from OPCAB, with the most benefit derived from reduced perioperative morbidity.51An analysis of the STS ACSD from 1997 to 2007 showed that there were 38% and 55% reductions in the odds of early mortality for patients undergoing off‐pump operations in the third‐ and fourth‐highest risk quartiles, respectively.52 In contrast, a study of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database for high‐risk patients associated OPCAB with reduced morbidity but showed similar operative mortality as compared to ONCAB.53Impaired Ventricular FunctionAs for patients with low ejection fraction (EF), an analysis of the STS ACSD from 2008 to 2011 of 25 667 patients with low EF (<30%) found that the risks of death, stroke, and major adverse cardiac events (MACE) were lower in the OPCAB group.54 These findings were corroborated by analysis of the Japan Adult Cardiovascular Surgery Database in which OPCAB was associated with reduced early morbidity and mortality in patients with EF <30%.55 A meta‐analysis of observational studies concluded that OPCAB may be associated with lower incidence of early mortality in patients with impaired left ventricular function but noted that the method of handling the conversion‐related mortality in each study was uncertain and may have influenced the results. In addition, incomplete revascularization (IR) in the OPCAB group occurred more often and may explain why the early advantage in mortality was not maintained long term.56Advanced AgeAdvanced age is a known risk factor in CABG.57 In a systematic review of 16 observational studies of CABG in octogenarians (18 685 ONCAB and 8938 OPCAB), in‐hospital mortality (pooled OR: 0.64; 95% CI, 0.44–0.93; P=0.02), and stroke (pooled OR: 0.61; 95% CI, 0.48–0.76; P 70 years.59 A propensity matched study of 6943 pairs of octogenarians showed a 30% reduction in the odds of stroke with OPCAB using the Nationwide Inpatient Sample (NIS).60 In addition, the largest RCT to date comparing OPCAB and ONCAB in elderly patients (aged ≥75 years), reported no significant difference between ONCAB and OPCAB with regard to the composite outcome of death, stroke, MI, repeat revascularization, or new renal replacement therapy within 30 days and 1 year after surgery.41Female SexNumerous studies report CABG mortality to be higher in women.61 In fact, according to the STS CABG risk model, female sex is associated with increased risk of operative mortality (OR: 1.31), major complications (OR: 1.18), and increased hospital length of stay (OR: 1.24).57 OPCAB, however, may narrow or eliminate this disparity in outcomes between women and men. A large study at an experienced OPCAB US academic center concluded that OPCAB disproportionately benefits women and narrows the sex disparity in outcomes after CABG. Female patients (n=3248) and those treated with OPCAB (n=4492) were older and had more comorbidities than male patients (n=8165) and those treated with ONCAB (n=6921), respectively. Women treated with ONCAB had risk‐adjusted ORs of 1.60 for death (P=0.01) and 1.71 for MACE (P<0.001) compared with men who had ONCAB. In contrast, women treated with OPCAB had outcomes similar to men who had either OPCAB or ONCAB. Among women, OPCAB was associated with a significant reduction in death (OR: 0.39; P=0.001) and MACE (OR: 0.43; P 100 OPCAB cases between 2004 and 2005. Women (n=11 785) and those treated with OPCAB (n=16 245) were older and had more comorbidities than men (n=30 662) and those treated with conventional ONCAB (n=26 202), respectively. The risk‐adjusted ORs for death and major complications were significantly lower with OPCAB than with ONCAB. Among ONCAB cases only, women had a significantly greater adjusted risk of death, prolonged ventilation, and longer hospital length of stay than men; however, among OPCAB cases, women had similar outcomes.64 A meta‐analysis of observational studies associated OPCAB with reduced perioperative MI but not with reduction of other morbidities or operative mortality.65 Of note, women undergoing OPCAB received fewer grafts than those undergoing ONCAB.OPCAB may have a selective benefit for women. The underlying mechanism is unclear and is unlikely to be related to avoidance of CPB because there is no major sex difference in outcomes associated with valve surgery.66 It is interesting, however, that women who undergo OPCAB are more likely to receive an internal mammary artery bypass than those undergoing ONCAB.67Neurological RiskThe possible association of OPCAB with reduced stroke with enhanced benefit in higher risk patients67 argues for a potential benefit in patients with a history of atheromatous aorta or cerebrovascular disease. A large single‐center study utilizing propensity‐matched analysis in patients with atheromatous disease of the ascending aorta associated ONCAB with an increased risk of postoperative stroke (OR: 1.4; P=0.05) and operative mortality.68 Another study associated OPCAB with reduced stroke and operative mortality in a similar population.69 Patients with carotid stenosis may have a potential benefit with OPCAB,70 but the evidence is inconclusive, and when it comes to combined CABG and carotid endarterectomy, again, the data are sparse, but both OPCAB and ONCAB may provide equivalent outcomes.71 In patients with a history of preoperative cerebrovascular events, OPCAB does not appear to confer a risk benefit with regard to postoperative neurological outcome compared with ONCAB.72 Of note, postoperative cognitive impairment is similar after on‐ and off‐pump CABG.73End Organ FailureThe data on the benefit of OPCAB in patients with end‐organ failure, including renal failure and cirrhosis, are limited to observational studies and mostly small patient numbers. Despite a higher rate of IR, a propensity‐matched analysis associated on‐pump with increased operative mortality in patients with advanced chronic kidney disease.74 A meta‐analysis including 17 studies with 2
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