Long-term clinical and angiographic outcomes in patients with diabetes undergoing coronary artery bypass graft surgery: results from the Project of Ex-vivo Vein Graft Engineering via Transfection IV trial.

BACKGROUND: There is limited information about the association between diabetes, its treatment, and long-term angiographic and clinical outcomes in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the association of diabetes and its treatment with 1-year angiographic graft failure and 5-year clinical outcomes in patients undergoing CABG. METHODS: Using data from 3,014 patients in PREVENT IV, we analyzed angiographic and clinical outcomes in patients with and without diabetes and among those who did and did not receive insulin before CABG. Logistic regression and Cox proportional hazards models were used to adjust for differences in baseline variables. RESULTS: Overall, 1,139 (37.8%) patients had diabetes. Of these, 305 (26.8%) received insulin. One-year rates of vein graft failure were similar in patients with and without diabetes but, among diabetics, tended to be higher in patients who received insulin compared with those who did not. At 5 years, rates of death, myocardial infarction, or revascularization were higher among patients with compared with those without diabetes (adjusted hazard ratio 1.57; 95% CI 1.26-1.96; P < .001) and, among diabetics, higher among those who received insulin (adjusted hazard ratio 1.15; 95% CI 1.02-1.30; P = .02). CONCLUSIONS: Patients with diabetes had similar rates of vein graft failure but worse clinical outcomes than patients without diabetes. Patients who received insulin had significantly worse clinical outcomes than patients who did not receive insulin. Further studies to better understand the mechanism behind these findings and to improve the outcomes of patients with insulin-requiring diabetes undergoing CABG surgery are warranted.

Endoscopic harvesting device type and outcomes in patients undergoing coronary artery bypass surgery.

OBJECTIVE: To evaluate angiographic and clinical outcomes associated with open and closed dissection tunnel endoscopic vein harvesting (EVH) devices. BACKGROUND: A previous PREVENT-IV (PRoject of Ex-vivo Vein graft ENgineering via Transfection IV) analysis reported that EVH for coronary artery bypass graft surgery was associated with worse outcomes than with traditional vein harvesting; however, outcomes by EVH device type were not available. METHODS: Using data from the PREVENT-IV trial, we compared 1549 patients from 75 surgical sites who underwent EVH with open (n = 390) or closed (n = 1159) harvest tunnel devices. Outcomes included the incidence of vein graft failure at 12 to 18 months and a composite of death, myocardial infarction, and revascularization through 5 years. RESULTS: Among patients undergoing open and closed tunnel EVH, no difference in the per-patient incidence of vein graft failure (43.8% vs 47.1%; adjusted odds ratio, 0.91; 95% confidence interval, 0.53-1.55; P = 0.724) or per-graft incidence of vein graft failure (25.5% vs 25.9%; adjusted odds ratio, 0.96; 95% confidence interval, 0.59-1.55; P = 0.847) was observed. At 5 years, no difference was observed in the primary composite clinical outcome between patients who underwent open and closed system EVH (21.5% vs 23.9%; adjusted hazard ratio, 0.85; 95% confidence interval, 0.66-1.10; P = 0.221). CONCLUSIONS: No differences in angiographic or clinical outcomes were observed among patients who underwent open versus closed tunnel endoscopic harvesting for coronary bypass surgery. These findings suggest that the risks associated with EVH that were reported in a previous PREVENT-IV analysis are not related to a specific EVH device.

Bayesian average error-based approach to sample size calculations for hypothesis testing.

Under the classical statistical framework, sample size calculations for a hypothesis test of interest maintain prespecified type I and type II error rates. These methods often suffer from several practical limitations. We propose a framework for hypothesis testing and sample size determination using Bayesian average errors. We consider rejecting the null hypothesis, in favor of the alternative, when a test statistic exceeds a cutoff. We choose the cutoff to minimize a weighted sum of Bayesian average errors and choose the sample size to bound the total error for the hypothesis test. We apply this methodology to several designs common in medical studies.

Edifoligide and long-term outcomes after coronary artery bypass grafting: PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) 5-year results.

BACKGROUND: Edifoligide, an E2F transcription factor decoy, does not prevent vein graft failure or adverse clinical outcomes at 1 year in patients undergoing coronary artery bypass grafting (CABG). We compared the 5-year clinical outcomes of patients in PREVENT IV treated with edifoligide and placebo to identify predictors of long-term clinical outcomes. METHODS: A total of 3,014 patients undergoing CABG with at least 2 planned vein grafts were enrolled. Kaplan-Meier curves were generated to compare the long-term effects of edifoligide and placebo. A Cox proportional hazards model was constructed to identify factors associated with 5-year post-CABG outcomes. The main outcome measures were death, myocardial infarction (MI), repeat revascularization, and rehospitalization through 5 years. RESULTS: Five-year follow-up was complete in 2,865 patients (95.1%). At 5 years, patients randomized to edifoligide and placebo had similar rates of death (11.7% and 10.7%, respectively), MI (2.3% and 3.2%), revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The composite outcome of death, MI, or revascularization occurred at similar frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%, respectively; hazard ratio 1.03 [95% CI 0.89-1.18], P = .721). Factors associated with death, MI, or revascularization at 5 years included peripheral and/or cerebrovascular disease, time on cardiopulmonary bypass, lung disease, diabetes mellitus, and congestive heart failure. CONCLUSIONS: Up to a quarter of patients undergoing CABG will have a major cardiac event or repeat revascularization procedure within 5 years of surgery. Edifoligide does not affect outcomes after CABG; however, common identifiable baseline and procedural risk factors are associated with long-term outcomes after CABG.

Primary Stability in Cementless Rotating Platform Total Knee Arthroplasty.

Highly porous ingrowth surfaces have been introduced into tibial tray fixation to improve long-term survivorship in cementless total knee arthroplasty. This study was designed to evaluate the effect of porous ingrowth surface on primary stability in the implanted cementless tibial component. Three tibial tray designs possessing sintered bead or roughened porous coating ingrowth surfaces were implanted into a foam tibia model with primary stability assessed via digital image correlation during stair descent and condylar liftoff loading. Follow-up testing was conducted by implanting matched-pair cadaveric tibias with otherwise identical trays with two iterations of ingrowth surface design. Trays were loaded and micromotion evaluated in a condylar liftoff model. The sintered bead tibial tray exhibited slightly lower micromotion than the roughened porous coating in stair descent loading. However, no significant difference in primary stability was observed in condylar liftoff loading in either foam or cadaveric specimens. Cementless tibial trays featuring two different iterations of porous ingrowth surfaces demonstrated both good stability in cadaveric specimens with less than 80 microns of micromotion and 1 mm of subsidence under cyclic loading. While improved ingrowth surfaces may lead to improved biological fixation and long-term osteointegration, this study was unable to identify a difference in primary stability associated with subsequent ingrown surface design iteration.

Role of diuretics, ß blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

OBJECTIVE: To examine the degree to which use of ß blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. DESIGN: Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. SETTING: NAVIGATOR trial. PARTICIPANTS: Patients who at baseline (enrolment) were treatment naïve to ß blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. MAIN OUTCOME MEASURES: Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. RESULTS: During the median five years of follow-up, ß blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas ß blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). CONCLUSIONS: Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of ß blockers was non-significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT00097786.

Admission, discharge, or change in B-type natriuretic peptide and long-term outcomes: data from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) linked to Medicare claims.

BACKGROUND: B-type natriuretic peptide (BNP) has been associated with short- and long-term postdischarge prognosis among hospitalized patients with heart failure. It is unknown if admission, discharge, or change from admission to discharge BNP measure is the most important predictor of long-term outcomes. METHODS AND RESULTS: We linked patients ≥65 years of age from hospitals in Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) to Medicare claims. Among patients with recorded admission and discharge BNP, we compared Cox models predicting 1-year mortality and/or rehospitalization, including clinical variables and clinical variables plus BNP. We calculated the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) for the best-fit model for each outcome versus the model with clinical variables alone. Among 7039 patients in 220 hospitals, median (25th, 75th) admission and discharge BNP were 832 pg/mL (451, 1660) and 534 pg/mL (281, 1111). Observed 1-year mortality and 1-year mortality or rehospitalization rates were 35.2% and 79.4%. The discharge BNP model had the best performance and was the most important characteristic for predicting 1-year mortality (hazard ratio for log transformation, 1.34; 95% confidence interval, 1.28 to 1.40) and 1-year death or rehospitalization (hazard ratio, 1.15; 95% confidence interval, 1.12 to 1.18). Compared with a clinical variables only model, the discharge BNP model improved risk reclassification and discrimination in predicting each outcome (1-year mortality: NRI, 5.5%, P<0.0001; IDI, 0.023, P<0.0001; 1-year mortality or rehospitalization: NRI, 4.2%, P<0.0001; IDI, 0.010, P<0.0001). CONCLUSIONS: Discharge BNP best predicts 1-year mortality and/or rehospitalization among older patients hospitalized with heart failure. Discharge BNP plus clinical variables modestly improves risk classification and model discrimination for long-term outcomes.