Survival estimates are an essential compliment to multivariable regression models for time-to-event data, both for prediction and illustration of covariate effects. They are easily obtained under the Cox proportional-hazards model. In populations defined by an initial, acute event, like myocardial infarction, or in studies with long-term followup, the proportional-hazards assumption of constant hazard ratios is frequently violated. One alternative is to fit an interaction between covariates and a prespecified function of time, implemented as a time-dependent covariate. This effectively creates a time-varying coefficient that is easily estimated in software such as SAS and R. However, the usual programming statements for survival estimation are not directly applicable. Unique data manipulation and syntax is required, but is not well documented for either software. This paper offers a tutorial in survival estimation for the time-varying coefficient model, implemented in SAS and R. We provide a macro coxtvc to facilitate estimation in SAS where the current functionality is more limited. The macro is validated in simulated data and illustrated in an application.

Objective To examine the degree to which use of β 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 β 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, β 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 β 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).

Background B-type natriuretic peptide (BNP) has been associated with short- and long-term post-discharge prognosis among hospitalized heart failure (HF) patients. 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 from hospitals in 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 [HR] for log transformation 1.34; 95% CI 1.28–1.40) and 1-year death or rehospitalization (HR 1.15; 95% CI 1.12–1.18). 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 HF. Discharge BNP plus clinical variables modestly improves risk classification and model discrimination for long-term outcomes.

W hen analyzing the results of a large randomized, controlled trial, patients are typically censored from end point analysis after the first occurrence of any component of the composite primary end points. This practice limits information to clinicians on the effect of the randomized therapy on subsequent events. Even though information is collected about subsequent (eg, second, third, fourth, etc.) efficacy and safety end point events for the duration Background-We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (eg, cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events. Methods and Results-In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios.

Objectives We undertook a meta-analysis to assess outcomes for drug-eluting (DES) and bare metal stents (BMS) in percutaneous coronary intervention (PCI) for unprotected left main coronary stenosis (LMCA). Background Uncertainty exits regarding the relative performance of DES versus BMS in unprotected LMCA PCI. Methods Of a total of 838 studies, 44 met inclusion criteria (N=10,342). The co-primary endpoints were mortality, myocardial infarction (MI), target vessel/target lesion revascularization (TVR/TLR), and major adverse cardiac events (MACE: mortality, MI, TVR/TLR). Results Event rates for DES and BMS were calculated at 6–12 months, at 2 years and at 3 years. Crude event rates at 3 years were: mortality (8.8% and 12.7%), MI (4.0% and 3.4%), TVR/TLR (8.0% and 16.4%), and MACE (21.4% and 31.6%). Nine studies were included in a comparative analysis (N=5,081). At 6–12 months the adjusted odds ratio (OR) for DES vs. BMS were: mortality 0.94 (95% confidence interval [CI] 0.06–15.48; p=0.97), MI 0.64 (95% CI 0.19–2.17; p=0.47), TVR/TLR 0.10 (95% CI 0.01–0.84; p=0.01) and MACE 0.34 (95% CI 0.15–0.78; p=0.01). At 2 years the OR were: mortality 0.42 (95% CI 0.28–0.62; p<0.01), MI 0.16 (95% CI 0.01–3.53; p=0.13), and MACE 0.31 (95% CI 0.15–0.66; p<0.01). At 3 years the OR were: mortality 0.70 (95% CI 0.53–0.92; p=0.01), MI 0.49 (95% CI 0.26–0.92; p=0.03), TVR/TLR 0.46 (95% CI 0.30–0.69; p<0.01), and MACE 0.78 (95% CI 0.57–1.07; p=0.12). Conclusion Our meta-analysis suggests that DES is associated with favorable outcomes for mortality, MI, TVR/TLR, and MACE as compared to BMS in unprotected LMCA PCI.

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 and to identify predictors of long-term clinical outcomes. Methods A total of 3014 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 measure was death, myocardial infarction (MI), repeat revascularization, and rehospitalization through 5 years. Results Five-year follow-up was complete in 2865 (95.1%) patients. At 5 years, patients randomized to edifoligide and placebo had similar rates of death (11.7% and 10.7%), MI (2.3% and 3.2%), revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The 5-year composite outcome of death, MI, or revascularization occurred at similar frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%; hazard ratio 1.03 [95% confidence interval 0.89–1.18]; P=0.721). Factors associated with death, MI, or revascularization at 5 years included diabetes, sex, worst graft quality, peri-index CABG MI, and ejection fraction. 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 following CABG; however, common identifiable baseline and procedural risk factors are associated with long-term outcomes following CABG.

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Objective To evaluate angiographic and clinical outcomes associated with open and closed tunnel dissection endoscopic vein harvesting (EVH) devices. Summary Background Data A previous PREVENT-IV analysis reported that EVH for coronary artery bypass graft (CABG) surgery was associated with worse outcomes compared 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, or 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 [OR], 0.91; 95% confidence interval [CI], 0.53 to 1.55; p=0.724) or per-graft incidence of vein graft failure (25.5% vs. 25.9%; adjusted OR, 0.96; 95% CI, 0.59 to 1.55; p=0.847) was observed. At 5 years, no difference was observed in the primary composite clinical outcome between open and closed system EVH patients (21.5% vs. 23.9%; adjusted hazard ratio, 0.85; 95% CI, 0.66 to 1.10; p=0.221). Conclusion No differences in angiographic or clinical outcomes were observed among patients who underwent open vs. 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.