Effect Of Off-pump Coronary Artery Bypass Grafting Research Articles

Simple randomization did not protect against bias in smaller trials

ObjectivesBy removing systematic differences across treatment groups, simple randomization is assumed to protect against bias. However, random differences may remain if the sample size is insufficiently large. We sought to determine the minimal sample size required to eliminate random differences, thereby allowing an unbiased estimation of the treatment effect. Study Design and SettingWe reanalyzed two published multicenter, large, and simple trials: the International Stroke Trial (IST) and the Coronary Artery Bypass Grafting (CABG) Off- or On-Pump Revascularization Study (CORONARY). We reiterated 1,000 times the analysis originally reported by the investigators in random samples of varying size. We measured the covariates balance across the treatment arms. We estimated the effect of aspirin and heparin on death or dependency at 30 days after stroke (IST), and the effect of off-pump CABG on a composite primary outcome of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days (CORONARY). In addition, we conducted a series of Monte Carlo simulations of randomized trials to supplement these analyses. ResultsRandomization removes random differences between treatment groups when including at least 1,000 participants, thereby resulting in minimal bias in effects estimation. Later, substantial bias is observed. In a short review, we show such an enrollment is achieved in 41.5% of phase 3 trials published in the highest impact medical journals. ConclusionsConclusions drawn from completely randomized trials enrolling a few participants may not be reliable. In these circumstances, alternatives such as minimization or blocking should be considered for allocating the treatment.

A meta-analysis of large randomized trials for mid-term major cardio- and cerebrovascular events following off-pump versus on-pump coronary artery bypass grafting

To determine whether off-pump coronary artery bypass grafting (CABG) increases mid-term major adverse cardiovascular (and cerebrovascular) events MACCE over on-pump CABG, we performed a meta-analysis of exclusive large randomized controlled trials (RCTs). Databases including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through October 2013 using Web-based search engines (PubMed and OVID). Eligible studies were RCTs of off-pump vs on-pump CABG enrolling >100 patients in each procedure and reporting MACCE at the time of >1 year follow-up. Mixed-effects meta-regression analyses were performed to determine whether the effects of off-pump CABG on MACCE were modulated by the prespecified factors. Eight RCTs enrolling 10 954 patients were identified and included. A pooled analysis demonstrated no statistically significant difference in off-pump and on-pump CABG (hazard ratio, 1.10; 95% confidence interval, 0.93-1.29; P = 0.27). In general, exclusion of any single study from the analysis did not substantially alter the overall result of our analysis. There was no evidence of significant publication bias. Meta-regression coefficients were not statistically significant for mean age, proportion of men and that of diabetes. In conclusion, off-pump CABG appears not to increase mid-term MACCE over on-pump CABG.

Invited Commentary

The population prevalence of patients receiving hemodialysis (HD) due to end stage renal disease is progressively increasing, and cardiovascular complications have been identified as the most common cause of death in these patients [1U.S. Renal Data System2011 Atlas of CKD and ESRD.http://www.usrds.org/atlas.aspxGoogle Scholar]. As a consequence, cardiac operations on HD patients are becoming more common. Traditionally, the results of myocardial revascularization in these patients have been poor because of advanced coronary disease and complications from the underlying condition. Indeed, guidelines from the European Society of Cardiology on myocardial revascularization suggest accounting for the general condition of the HD patient and life expectancy when considering a revascularization strategy [2Kolh P. Wijns W. Danchin N. et al.Guidelines on myocardial revascularization.Eur J Cardiothorac Surg. 2010; 38: S1-S52Crossref PubMed Scopus (316) Google Scholar]. The article by Takami and colleagues provides important new data on predictors of early and late outcomes after coronary artery bypass grafting (CABG) in HD patients [3Takami Y. Tajima K. Kato W. et al.Predictors for early and late outcomes after coronary artery bypass grafting in hemodialysis patients.Ann Thorac Surg. 2012; 94: 1940-1946Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar]. In their retrospective analysis of 152 HD patients, the authors found a significant reduction in hospital mortality with the introduction of an off-pump coronary artery bypass (OPCAB) in 2003. Early mortality decreased from 15.3% in the pre-OPCAB era to 6.3% afterward. Crude mortality in these patients is still significantly higher that in the general CABG population, but the improvement associated with the introduction of OPCAB in their experience was noteworthy. The effect of off-pump CABG on renal function in non-HD patients remains controversial [4Lamy A. Devereaux P.J. Prabhakaran D. et al.Off-pup or on-pump coronary artery bypass grafting at 30 days.N Eng J Med. 2012; 366: 1489-1497Crossref PubMed Scopus (530) Google Scholar, 5Elmistekawy E. Chan V. Bourke M.E. et al.Off-pump coronary artery bypass grafting does not preserve renal function better than on-pump coronary artery bypass grafting: results of a case-matched study.J Thorac Cardiovasc Surg. 2012; 143: 85-92Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar], but OPCAB may confer a clear benefit in the specific subgroup of HD patients. One may speculate as to the possible mechanisms leading to this association, with OPCAB potentially resulting in less manipulations of the aorta, a lower need for transfusion, volume replacement and hemodilution, and therefore fewer strokes, a shorter duration of mechanical ventilation, and a lower incidence of infections. Another important finding of this study was that the long-term survival of HD patients who underwent CABG appeared equivalent to that of HD patients who did not undergo myocardial revascularization. Thus, despite the high early mortality, CABG effectively returns HD patients to their life expectancy curve. Although indication bias in selecting patients was likely in Takami's study, this finding carries important implications for the patient and clinician when considering HD patients for coronary surgery. External validation by further studies will be needed to confirm whether OPCAB is indeed the optimal strategy for myocardial revascularization in HD patients. Moreover, future studies may consider the role of minimally invasive procedures such as minimally invasive cardiac surgery-CABG in further reducing surgical trauma [6McGinn Jr, J.T. Usman S. Lapierre H. Pothula V.R. Mesana T.G. Ruel M. Minimally invasive coronary artery bypass grafting: dual-center experience in 450 consecutive patients.Circulation. 2009; 120: S78-S84Crossref PubMed Scopus (139) Google Scholar], considering that mediastinitis is the most common fatal complication in HD patients after conventional surgery [7Liu J.Y. Birkmeyer J.O. Sanders J.H. et al.Risk of morbidity and mortality in dyalisis patients undergoing coronary artery bypass surgery.Circulation. 2000; 102: 2973-2977Crossref PubMed Scopus (192) Google Scholar]. Predictors for Early and Late Outcomes After Coronary Artery Bypass Grafting in Hemodialysis PatientsThe Annals of Thoracic SurgeryVol. 94Issue 6PreviewMarkedly higher hospital and long-term mortality after coronary artery bypass grafting (CABG) have been reported in hemodialysis (HD)-dependent patients. We tried to identify the predictors for short-term and long-term outcomes after CABG, which have not been well studied. Full-Text PDF

Coronary Artery Bypass Operations for Elderly Patients in California, 2003 to 2008

Coronary artery bypass grafting (CABG) is no longer rare for elderly patients. This study evaluates operative mortality and the effects of off-pump CABG (OPCAB) on mortality for elderly Californians between 2003 and 2008. All isolated CABGs in California for 2003 to 2008 were classified into cohorts by age: (1) younger than 75, (2) 75 to 84, and (3) 85 or older. Multivariable logistic regression models were developed for operative mortality. Trend analyses for observed and predicted mortality, and observed-to-expected mortality ratios were performed. The "recycled predictions" method was used to assess the effect of OPCAB on operative mortality. Among 101,710 isolated CABGs between 2003 and 2008, 22.0% were in cohort 2 and 2.3% were in cohort 3. Predicted mortality was unchanged for cohorts 2 and 3 (all p > 0.05), but observed-to-expected mortality ratios declined from 0.958 to 0.633 for cohort 2 (p = 0.021) and from 1.027 to 0.965 for cohort 3 (p = 0.168). The proportion of OPCAB for patients aged 75 years or older increased from 25.0% to 29.1% between 2003 and 2008. The adjusted odds ratio for operative mortality for OPCAB in patients aged 75 years or older was 0.752 (95% confidence interval, 0.650 to 0.871; p < 0.001) compared with on-pump CABG for the same age cohort. In California, overall predicted mortality was unchanged for elderly patients between 2003 and 2008, but operative mortality significantly decreased for patients aged 75 to 84. Improvement for CABG patients aged 85 years or older was insignificant. The increase in the number of OPCAB patients was associated with decreased mortality for elderly patients.

Off-pump vs. on-pump CABG: are we any closer to a resolution?

This editorial refers to ‘Off-pump vs. on-pump coronary artery bypass surgery: an updated meta-analysis and meta-regression of randomized trials’, by J. Afilalo et al. , doi:10.1093/eurheartj/ehr307 Afilalo and colleagues have presented an updated meta-analysis and meta-regression of randomized trials of off-pump vs. on-pump coronary artery bypass grafting (CABG) surgery.1 Their two major findings are that while there was a reduction in mortality, myocardial infarction, and stroke in the off-pump group, this only reached significance for the latter, and that the effect of off-pump CABG was similar on all clinical outcomes regardless of age, gender, number of grafts, and trial publication date. The two key questions are: (i) Are these conclusions justifiable based on the data presented? (ii) How relevant are the findings to routine clinical practice? Before answering these questions it is worth addressing (i) the current situation with off-pump CABG and (ii) the appropriateness of the nature and conduct of the meta-analysis and the meta-regression analysis. Off-pump surgery was initially proposed almost three decades ago2 to allow CABG in developing countries without the need for cardiopulmonary bypass that was beyond the economic reality of vast numbers of potential patients. Despite initial scepticism about its technical feasibility, off-pump CABG was gradually adopted by some surgeons in developed countries who believed that the elimination of cardiopulmonary bypass could potentially and substantially eliminate the adverse clinical consequences of extracorporeal circulation. In developed countries this was particularly relevant in a progressively elderly population undergoing cardiac surgery in view of their greater burden of existing co-morbidities and their greater susceptibility to the potentially deleterious consequences of cardiopulmonary bypass. On the other hand, critics maintained that off-pump surgery led to inferior revascularization through a reduction in both the number and quality of bypass grafts and that no study appeared to demonstrate any substantial clinical …

Abstract 2303: The Short-term Benefits of Off-pump Coronary Artery Bypass for Diabetes Patients Disappears in the Long Run

Numerous studies revealed the adverse impacts of diabetes on the outcomes of coronary artery bypass grafting (CABG). However, the disparities of impacts of different surgical techniques on the prognosis of diabetes and non-diabetes patients were still unknown. The objective of this study was to evaluate the possible beneficial effects of off-pump CABG (OPCAB) on the immediate as well as long term postoperative outcomes. From 1999 to 2005, 5550 consecutive patients underwent isolated conventional CABG (cCABG) or OPCAB in our institute. All patients have finished a 3-year follow up. In-hospital MACE includes cardiac death, stroke and myocardial infarction. As for MACE in the follow-up, the definition was the combination of cardiac death, stroke, myocardial infarction and revascularization. These data were prospectively collected and retrospectively reviewed. After risk adjustment, diabetes patients in cCABG group had an OR of 1.385 (p&lt;0.001) for immediate mortality and 1.291 (p&lt;0.010) for immediate MACE comparing with non-diabetes patients receiving cCABG. On the contrary, no significant differences were found when comparisons between diabetes and non-diabetes patients undergoing OPCAB were carried out, indicating beneficial effects of OPCAB for diabetes patients in short terms. However, while the risk-adjusted HR of diabetes patients for long-term mortality and for long-term MACE in cCABG group were 1.130 (p=0.003) and 1.781 (p=0.001) respective, those in OPCAB group were 1.082 (p=0.077) and 1.038 (p&lt;0.001). These results suggested that although the beneficial effects of OPCAB for diabetes patients in terms of mortality still remained, those in terms of long-term MACE disappeared. Although reductions of differences of in-hospital adverse outcomes between diabetes and non-diabetes patients undergoing OPCABG were seen, these beneficial effects were mitigated in the long run.

Meta-analysis of short-term and mid-term outcomes following off-pump coronary artery bypass grafting

Background Uncertainty continues to surround the relative benefits and harms of conventional coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCABG). Possible reasons are that high-quality studies have not comprehensively examined relevant patient outcomes and have enrolled a limited range of patients. Some studies may have been too small to detect clinically important differences in patient outcomes. The present study addresses these issues using meta-analysis. Methods We comprehensively retrieved randomized and nonrandomized controlled studies according to predetermined criteria. We performed meta-analyses for each outcome and empirically determined whether potential biases that might result from differences in study design or patient characteristics actually biased a study's results. We also conducted sensitivity analyses and tested for publication bias. Results Rates of perioperative myocardial infarction, stroke, reoperation for bleeding, renal failure, and mortality were lower after OPCABG than after CABG. Reductions in length of hospital stay, atrial fibrillation, and wound infection were also associated with OPCABG, but statistically significant differences among study results for these outcomes could not be explained by available information. Midterm (3 to 25 months) angina recurrence did not appear to differ between treatments; a trend was noticed toward lower reintervention rates with CABG, and a trend toward lower overall mortality with OPCABG, at least when performed at experienced centers. These midterm outcome results require confirmation. Conclusions Off-pump coronary artery bypass grafting appears to reduce length of hospital stay, operative morbidity, and operative mortality relative to on-pump CABG. More studies are required before firm conclusions can be drawn concerning the effect of OPCABG on midterm mortality, angina recurrence, and repeat intervention.