Graft Failure After Coronary Artery Bypass Grafting and Its Association With Patient Characteristics and Clinical Events: A Pooled Individual Patient Data Analysis of Clinical Trials With Imaging Follow-Up.

BACKGROUND: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. METHODS: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. RESULTS: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (interquartile range [IQR], 1.00-1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01-1.15]; P=0.03), female sex (aOR, 1.27 [95% CI, 1.08-1.50]; P=0.004), and smoking (aOR, 1.20 [95% CI, 1.04-1.38]; P=0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63-0.88]; P<0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54-4.47]; P<0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86-3.62]; P<0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01-3.89]; P<0.001). CONCLUSIONS: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.

Ticagrelor versus aspirin and vein graft patency after coronary bypass: A randomized trial.

BACKGROUND: Antiplatelet therapy prevents saphenous vein graft (SVG) occlusion and improves outcomes after coronary artery bypass graft surgery (CABG). However, the optimal postoperative antiplatelet regimen remains unclear. The goal of the Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) trial was to assess whether early postoperative ticagrelor reduces SVG occlusion compared to conventional aspirin therapy. METHODS: In this multi-center double-blind randomized trial, 250 patients who had CABG with SVG were randomized to receive either aspirin 81 mg twice daily or ticagrelor 90 mg twice daily. The primary outcome was SVG occlusion at 1 year. RESULTS: Altogether, 123 patients were randomized to aspirin and 127 received ticagrelor. One-year graft assessment was performed in 202 patients (80.8%), examining 588 grafts, yielding an overall graft occlusion rate of 10.9%. The primary outcome, SVG occlusion at 1 year, did not significantly differ between the two groups (17.4% vs. 13.2%, aspirin vs. ticagrelor, p = .30). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (21.5% vs. 22.3%, aspirin vs. ticagrelor, p = .90), and the number of patients with vein graft disease did not significantly differ between the groups (29.4% vs. 28.0%, aspirin vs. ticagrelor, p = .88). Freedom from major adverse cardiovascular events at 1 year was similar between the groups (p = .60). CONCLUSIONS: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft occlusion 1 year after CABG. Further study will assess the impact of ticagrelor on 2-year graft patency for this cohort.

Ticagrelor versus aspirin 2 years after coronary bypass: Observational analysis from the TARGET trial.

BACKGROUND: Compared to conventional aspirin therapy, ticagrelor did not improve vein graft patency 1 year after coronary bypass surgery (CABG) in the ticagrelor antiplatelet therapy to reduce graft events and thrombosis (TARGET) trial. However, it is unknown whether ticagrelor may impact graft patency long-term following surgery. METHODS: In the TARGET multicenter trial, 250 CABG patients were randomized to aspirin 81 mg or ticagrelor 90 mg twice daily. In this observational analysis, 2 years after surgery, vein graft occlusion and clinical events were compared among subjects who agreed to a second year of double-blind study drug administration (N = 156). RESULTS: Two-year graft assessment was performed for 142 patients (80 aspirin patients, 62 ticagrelor patients, 425 total grafts), with an overall 2-year graft occlusion rate of 10.6%. Vein graft occlusion at 2 years, the primary outcome of this study, did not significantly differ between the two groups (15.7% vs. 13.2%, aspirin vs. ticagrelor, p = .71). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (19.4% vs. 19.8%, aspirin vs. ticagrelor, p = 1.00), and the number of patients with vein graft disease did not significantly differ between the groups (30.0% vs. 29.0%, aspirin vs. ticagrelor, p = 1.00). Vein grafts developing new disease did not significantly differ between the two groups (1.5% vs. 3.8%, aspirin vs. ticagrelor, p = .41). Freedom from major adverse cardiovascular events at 2 years was similar between the groups (p = .75). CONCLUSION: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft disease 2 years after CABG.

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Importance: The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. Objective: To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. Data Sources: MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. Study Selection: Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. Data Extraction and Synthesis: Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. Main Outcomes and Measures: The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. Results: A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46). Conclusions and Relevance: Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

Impact of lipid levels and high-intensity statins on vein graft patency after CABG: Midterm results of the ACTIVE trial.

BACKGROUND: High-dose atorvastatin did not improve 1-year vein graft patency in the recent Aggressive Cholesterol Therapy to Inhibit Vein Graft Events trial. However, it remains unknown whether high-intensity statins may impact graft disease in the years that follow. METHODS: In the trial, patients (N = 173) were randomized to receive atorvastatin 10 or 80 mg for 1 year after coronary bypass surgery (CABG). Beyond 1 year, the choice of statin was left to the patient's physician. In this study of participants who agreed to follow-up (N = 76), low-density lipoprotein (LDL) levels were measured and graft patency was assessed 3 years after surgery. RESULTS: The rate of vein graft disease 3 years after surgery was not significantly reduced with atorvastatin 80 mg during the first postoperative year or the use of open-label high-intensity statin thereafter (p = NS). However, a trend was observed between higher LDL levels during the first postoperative year and a greater incidence of vein graft disease at 3 years (p = .12). Among patients who had LDL levels more than 90 mg/dl in the first year after CABG, 38.5% had vein graft disease at 3 years, compared to 19.0% for those with LDL levels less than 90 mg/dl (p = .15). Higher mean LDL levels during the first postoperative year were associated with a higher rate of vein disease 3 years after surgery both at the graft level (p = .03) and at the patient level (p = .03) in multivariate analysis. CONCLUSIONS: Higher LDL levels during the first postoperative year were associated with significantly greater vein graft disease 3 years after CABG.

Quality of life after coronary artery bypass graft surgery versus percutaneous coronary intervention: what do the trials tell us?

PURPOSE OF REVIEW: With an ever-aging population, the treatment of multi-vessel coronary artery disease (CAD) has increasingly become focused not only on mortality, but on symptom relief and improving quality of life (QOL). The purpose of this review is to present a summary on the subject of QOL after percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG), highlighting the latest comparative trials in the field. RECENT FINDINGS: About 1 month after revascularization, patients recovering from either PCI or CABG report improvements in angina frequency. However, at 6 months and in the years that follow, angina relief is significantly better after CABG compared with PCI. Correspondingly, the use of antiangina medication is significantly higher following PCI, even in recent years with the use of drug-eluting stents. Regarding general health status, at the 1-month time point, PCI patients have recovered faster than those who have had surgery, reporting fewer physical limitations, less bodily pain, and greater QOL and treatment satisfaction. Nevertheless, these differences disappear by 6 months, and in the years thereafter, CABG patients report fewer physical limitations compared with those who have undergone PCI. About 5 years after revascularization, significant benefits remain favoring CABG in term of physical, emotional, and mental health. SUMMARY: Patients with multivessel coronary artery disease attain important QOL benefits following revascularization with either PCI or CABG. Percutaneous treatments lead to a more rapid recovery and improved short-term health status compared with CABG at 1 month. However, surgery results in greater angina relief and improved QOL compared with PCI 6 months after revascularization and beyond.

Secondary prevention after coronary artery bypass graft surgery: a primer.

PURPOSE OF REVIEW: Despite the benefits of surgical coronary revascularization, patients continue to be at risk for ischemic events in the years that follow coronary artery bypass graft surgery (CABG), mandating the role for postoperative secondary preventive therapy. The purpose of this review was to present a summary on the subject of secondary prevention after CABG, including an overview of a recently published scientific statement, and highlight the newest studies in the field. RECENT FINDINGS: Aspirin and statin therapy continue to be the mainstay of secondary prevention after CABG, although newer antiplatelet and lipid-lowering medicines are being actively studied for their potential benefits. Other important elements to secondary prevention after CABG include the aggressive management of hypertension, smoking cessation, and the initiation of cardiac rehabilitation. SUMMARY: Secondary prevention is an essential component of postoperative care after CABG. Instituting preventive therapies after surgery optimizes graft patency and helps patients achieve the highest level of physical health and quality of life following CABG.

Impact of clopidogrel plus aspirin versus aspirin alone on the progression of native coronary artery disease after bypass surgery: analysis from the Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) randomized trial.

BACKGROUND: The effects of dual antiplatelet therapy with aspirin and clopidogrel on the progression of native coronary artery disease after coronary artery bypass grafting are unknown. METHODS AND RESULTS: In the Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) trial, a total of 113 patients were randomized to receive aspirin plus clopidogrel or aspirin plus placebo for 1 year after coronary artery bypass grafting. In this secondary analysis, the 92 patients who underwent preoperative and 1-year postoperative angiograms at 2 centers had each of their coronary stenoses graded serially by using 6 thresholds (grade 0 [0%-24%], grade 1 [25%-37%], grade 2 [38%-62%], grade 3 [63%-82%], grade 4 [83%-98%], and grade 5 [99%-100%]). We compared the incidence and degree of evolving coronary artery disease between the 2 treatment groups. A total of 543 preoperative stenoses and occlusions were quantified and followed. At 1-year postoperatively, there were 103 evolving (94 worsened, 9 improved) and 22 new lesions. The right coronary artery territory and sites proximal to a graft were more commonly associated with worsening coronary artery disease (P≤0.02). There were no differences in clinical events between treatment groups, and the proportion of patients with evolving or new lesions was also similar (70% versus 74%, aspirin-clopidogrel versus aspirin-placebo, respectively; P=0.8). However, in evolving or new lesions, the mean grade change (1.1±1.0 versus 1.6±1.1, respectively; P=0.01) and the proportion of new occlusions (7% versus 22%; P=0.02) were lower in the aspirin-clopidogrel group. CONCLUSIONS: The addition of clopidogrel to aspirin correlates with less worsening of native coronary artery disease 1 year after coronary artery bypass grafting. These findings may help guide post-coronary artery bypass grafting antiplatelet therapy. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

Non-steroidal anti-inflammatory drug administration after coronary artery bypass surgery: utilization persists despite the boxed warning.

PURPOSE: In 2005, the US Food and Drug Administration (FDA) issued a boxed warning against the administration of non-steroidal anti-inflammatory drugs (NSAIDs) after coronary artery bypass graft (CABG) surgery because of cardiovascular safety concerns. We assessed utilization rates before and after the advisory and evaluated predictors of NSAID administration following CABG. METHODS: We assembled a cohort of 277,576 patients who underwent CABG from 2004 to 2010. Temporal trends in NSAID exposure were evaluated, and predictors of postoperative NSAID use were identified using generalized estimating equations. RESULTS: Over the study period, 92,938 CABG patients (33.5%) received NSAIDs following surgery. The frequency of NSAID administration declined steadily over time, from a peak of 38.9% in 2004 to a low of 29.0% in 2010 (p < 0.0007). Ketorolac was the most frequent NSAID prescribed, commonly on the first postoperative day. Surgery performed after the boxed warning was independently associated with a 20% lower odds of NSAID administration [odds ratio (OR): 0.80; p = 0.0003]. Other factors that predicted a lower odds of NSAID use following surgery included a history of renal disease (OR: 0.33; p < 0.0001) and liver disease (OR: 0.66; p < 0.0001), and the need for concurrent valve surgery (OR: 0.78; p < 0.0001). A mammary graft at the time of surgery increased the odds of NSAID administration (OR: 1.23; p < 0.0001). CONCLUSIONS: The frequency of NSAID administration after CABG has declined since the FDA advisory, yet many patients continue to receive them in recent years. Our data highlight the need for future research initiatives to further define the risks associated with NSAID use in this population.

Coronary bypass surgery in the presence of metastatic pheochromocytoma.

The hemodynamic management of a patient with a pheochromocytoma presents special challenges due to the episodic release of catecholamines from the tumor, which threatens to provoke a hypertensive crisis. We present a patient with metastatic pheochromocytoma (bone, lung, lymph nodes) who underwent successful coronary artery bypass graft (CABG) surgery following premedication with phenoxybenzamine and metyrosine as well as the use of intraoperative phentolamine for the management of a hypertensive crisis in the operating room.

Correlates of saphenous vein graft hyperplasia and occlusion 1 year after coronary artery bypass grafting: analysis from the CASCADE randomized trial.

BACKGROUND: Intimal hyperplasia of saphenous vein grafts (SVGs) can lead to subsequent graft atherosclerosis and occlusion after coronary artery bypass grafting (CABG). This study examined whether patient characteristics, anatomic factors, and medications are associated with SVG intimal hyperplasia and occlusion after CABG. METHODS AND RESULTS: We performed a post hoc analysis of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial, where 322 grafts were assessed by angiography and 90 grafts were examined by intravascular ultrasound at 1 year after CABG. We assessed the following correlates for intimal hyperplasia and occlusion: patient characteristics, discharge medications, target vessel characteristics, and SVG diameter. At 1 year, the SVG mean intimal area was 4.3 ± 2.1 mm(2), and the occlusion rate was 6.2% (13/209). Independent correlates of hyperplasia were larger SVG diameter (1.9 ± 0.2 mm(2)/mm; P<0.001), hypertension (0.7 ± 0.3 mm(2); P=0.03), and grafting to the right coronary territory (0.6 ± 0.3 mm(2); P=0.03), whereas statin (-0.8 ± 0.3 mm(2); P=0.01) and ß-blocker use (-1.0 ± 0.4 mm(2); P=0.03) were associated with less hyperplasia. Low target vessel quality was an independent correlate of SVG occlusion (odds ratio, 5.2 ± 3.1; P<0.01). CONCLUSIONS: Hypertension, SVG diameter, grafting to the right coronary artery, and low quality of the target vessel correlate with the development of SVG hyperplasia or occlusion by 1 year after CABG, whereas ß-blockers and statins are associated with less SVG disease. These new findings further our understanding of SVG remodeling after bypass surgery and may guide future research to help prevent post-CABG SVG disease. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

Full prescription coverage versus usual prescription coverage after coronary artery bypass graft surgery: analysis from the post-myocardial infarction free Rx event and economic evaluation (FREEE) randomized trial.

BACKGROUND: Eliminating out-of-pocket costs for patients after myocardial infarction (MI) improves adherence to preventive therapies and reduces clinical events. Because adherence to medical therapy is low among patients treated with coronary artery bypass graft surgery (CABG), we evaluated the impact of providing full prescription coverage to this patient subgroup. METHODS AND RESULTS: The MI Free Rx Event and Economic Evaluation (FREEE) trial randomly assigned 5855 patients with MI to full prescription coverage or usual formulary coverage for all statins, ß-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. We assessed the impact of full prescription coverage on adherence, clinical outcomes, and healthcare costs using adjusted models among the 1052 patients who underwent CABG at the index hospitalization and 4803 who did not. CABG patients were older and had more comorbid illness (P<0.01). After MI, CABG patients were significantly more likely to receive ß-blockers and statins but were less likely to receive angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy (P<0.01). Receiving full drug coverage increased rates of adherence to all preventative medications after CABG (all P<0.05). Full coverage was also associated with nonsignificant reductions in the rate of major vascular events or revascularization for patients treated with CABG (hazard ratio, 0.91; 95% confidence interval, 0.66-1.25) or without CABG (hazard ratio, 0.93; 95% confidence interval, 0.82-1.06), with no interaction noted (Pint=NS). After CABG, full prescription coverage significantly reduced patient out-of-pocket spending for drugs (P=0.001) without increasing overall health expenditures (P=NS). CONCLUSIONS: Eliminating drug copayments after MI provides consistent benefits to patients treated with or without CABG, leading to increased medication adherence, trends toward improved clinical outcomes, and reduced patient out-of-pocket expenses.

Black box warning: is ketorolac safe for use after cardiac surgery?

OBJECTIVE: In 2005, after the identification of cardiovascular safety concerns with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), the FDA issued a black box warning recommending against the use of NSAIDs following cardiac surgery. The goal of this study was to assess the postoperative safety of ketorolac, an intravenously administered NSAID, after cardiac surgery. DESIGN: Retrospective observational study. SETTING: Single center, regional hospital. PARTICIPANTS: A total of 1,309 cardiac surgical patients (78.1% coronary bypass, 28.0% valve) treated between 2006 and 2012. INTERVENTIONS: A total of 488 of these patients received ketorolac for postoperative analgesia within 72 hours of surgery. MEASUREMENT AND MAIN RESULTS: Ketorolac-treated patients were younger, had better preoperative renal function, and underwent less complex operations compared with non-ketorolac patients. Ketorolac was administered, on average, 8.7 hours after surgery (mean doses: 3.1). Postoperative outcomes for ketorolac-treated patients were similar to those expected using Society of Thoracic Surgery database risk-adjusted outcomes. In unadjusted analysis, patients who received ketorolac had similar or better postoperative outcomes compared with patients who did not receive ketorolac, including gastrointestinal bleeding (1.2% v 1.3%; p = 1.0), renal failure requiring dialysis (0.4% v 3.0%; p = 0.001), perioperative myocardial infarction (1.0% v 0.6%; p = 0.51), stroke or transient ischemic attack (1.0% v 1.7%; p = 0.47), and death (0.4% v 5.8%; p<0.0001). With adjustment in a multivariate model, treatment with ketorolac was not a predictor for adverse outcome in this cohort (odds ratio: 0.72; p = 0.23). CONCLUSIONS: Ketorolac appears to be well-tolerated for use when administered selectively after cardiac surgery. Although a black box warning exists, the data highlights the need for further research regarding its perioperative administration.

Acute type A aortic dissection with cardiac tamponade: unexpected late survival without aortic surgery.

Acute type A aortic dissection complicated by cardiac tamponade portends a lethal prognosis. We report the unusual case of an older female who unexpectedly survived for more than one year after presentation with acute dissection and tamponade. She was treated with a pericardial window and remains alive now four years after presentation.

Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Renin-angiotensin-system modulators and the incidence of atrial fibrillation following hospitalization for coronary artery disease.

AIMS: Previous studies have suggested that upstream medical therapy to modulate the renin-angiotensin axis may facilitate left atrial remodelling and thereby prevent new-onset atrial fibrillation (AF). The purpose of this study was to evaluate the association between angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB) on new-onset AF in a large cohort of patients with coronary artery disease (CAD). METHODS AND RESULTS: This was a population-based study of 28 620 patients, from community-dwelling Medicare beneficiaries who had been hospitalized for acute myocardial infarction or coronary revascularization (1995-2004). All patients, 65 years and older, had a mean follow-up period of upto 3.8 ± 3.0 years. Patients with a history of AF before and during hospitalization were excluded. We compared the incidence of new-onset AF between patients who were (N= 10 918) and were not (N= 17 702) prescribed ACEI and/or ARB within 1 month of hospital discharge following cardiac event. New-onset AF within 5 and 10 years was 39.1 and 61.1%, respectively, in patients who received ACEI/ARB, compared 34.9 and 53.6% in patients who did not receive them [unadjusted hazard ratio (HR): 1.16; 95% confidence interval (CI): 1.11, 1.21]. Multivariable analysis adjusting for patient- and hospital-related characteristics indicated that ACEI/ARB use independently had no impact on the risk of developing new-onset AF compared with non-users (adjusted HR: 0.99; 95% CI: 0.94, 1.04). Adjustment for propensity-score and health-seeking behaviours yielded nearly identical results. CONCLUSION: Angiotensin converting enzyme inhibitor/ARB therapy initiated within 1 month after hospital discharge is not associated with a reduction in the risk of new-onset AF after myocardial infarction or coronary revascularization.

Long-term clinical and hemodynamic performance of the Hancock II versus the Perimount aortic bioprostheses.

BACKGROUND: The Medtronic Hancock II and the Carpentier-Edwards Perimount are among the world's most commonly used aortic bioprostheses. However, a direct comparison of their clinical performance is lacking. To minimize biases inherent to between-center comparisons, we examined these prostheses within a large, contemporary, single-center cohort. METHODS AND RESULTS: Between 1990 and 2007, 1659 patients (mean age, 73.1±9.3 years) underwent aortic valve replacement with either the Hancock II (N=1021) or the Perimount (N=638). Patients were prospectively followed-up with serial clinic visits and echocardiograms for up to 16 years (mean, 5.0±3.3 years). There was no significant difference in aortic root size preoperatively (P=0.7). Aortic root enlargement was more commonly performed with the Perimount (P<0.001), and the manufacturer valve size of the implanted prosthesis was larger with the Hancock II (P<0.001). Postoperatively, peak and mean transprosthesis gradients were higher for the Hancock II (32.7±0.7 and 16.0±0.3 mm Hg, respectively) than for the Perimount (24.9±0.7 and 13.4±0.4 mm Hg, respectively; P<0.001). However, no difference in left ventricular mass regression was observed at late follow-up (P=0.9). Unadjusted 10-year survival was 59.4%±2.4% for the Hancock II and 70.2%±3.8% for the Perimount (P=0.07). Multivariable predictors of survival did not include prosthesis type (P=0.2). CONCLUSIONS: For the same manufacturer valve size, the Perimount is larger, which may warrant enlarging the aortic root more often, and it is associated with better hemodynamics than the Hancock II. These differences do not impact survival or left ventricular mass regression, and the long-term clinical performances of the Hancock II and Perimount bioprostheses are equivalent.

Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial.

BACKGROUND: clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. METHODS AND RESULTS: in this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1 ± 2.0 versus 4.5 ± 2.1 mm(2), aspirin-clopidogrel versus aspirin-placebo, P=0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group (P=0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group (P=0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9 ± 3.4% in the aspirin-clopidogrel group and 91.1 ± 3.8% in the aspirin-placebo group (P=0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P=0.50). CONCLUSIONS: compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting.