Bach, Richard G.

Background Despite guideline recommendations, a significant number of patients with non– ST elevation myocardial infarction ( NSTEMI ) do not receive dual antiplatelet therapy ( DAPT ) before angiography “pretreatment.” While there may be valid clinical reasons to not pretreat, such as concern for bleeding or multivessel disease warranting coronary artery bypass graft surgery, the degree of variability and factors associated with DAPT pretreatment are unknown. Methods and Results From the multicenter TRIUMPH registry, 1632 NSTEMI patients were not taking DAPT on admission and were included in the study cohort. Among the study patients, only 22% patients received DAPT pretreatment. A multivariable logistic regression model showed that race other than white or black (odds ratio [ OR] 0.41, 95% CI 0.21–0.83), hemoglobin level ( OR 1.18, 95% CI 1.08–1.29), patients’ bleeding risk (assessed with NCDR Cath PCI Bleeding Risk Score) ( OR 0.85, 95% CI 0.74–0.99), and severe left ventricular dysfunction ( OR 0.3, 95% CI 0.13–0.65) were the main predictors of pretreatment with DAPT , whereas likelihood of needing coronary artery bypass graft surgery ( GRACE prediction model) was not ( OR 1.09, 95% CI 0.88–1.35). Median ORs were calculated to assess variability of receiving DAPT pretreatment across sites after adjustment for patient characteristics. Receiving DAPT pretreatment varied substantially across sites (range 0–100%, mean OR 3.94, P <0.0001). Conclusions While deviating from guideline‐recommended DAPT pretreatment in patients with NSTEMI was associated with patient factors (eg, bleeding risk), marked variation was present across sites after accounting for patient‐level characteristics. This suggests that site‐level interventions are needed to improve concordance with current guidelines.

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation. © 2013 Wiley Periodicals, Inc.

Background —The impact of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) on long-term mortality rates in the presence of various demographic, clinical, and angiographic factors is uncertain in the population of patients suitable for both procedures. Methods and Results —In the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial and registry, 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992. Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality, with particular attention to factors that interact with treatment. Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG (relative risk [RR] 1.78 and 2.63, respectively, P <0.001), and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA (RR 4.08, P <0.001). Factors most strongly associated with high overall mortality rates were insulin-treated diabetes, congestive heart failure, kidney failure, and older age. Black race was also associated with higher mortality rates (RR 1.49, P =0.019). Conclusions —A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization.

Background —Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. Methods and Results —Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients ( P =0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively ( P =0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG ( P =0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6.0%, respectively ( P =0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. Conclusions —BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Background— Coronary artery disease (CAD) is the major cause of death in patients with type 2 diabetes mellitus. Although demographic and clinical factors associated with extent of CAD in patients with diabetes mellitus have been described, genetic factors have not. We hypothesized that genetic variation in peroxisome proliferator-activated receptor (PPAR) pathway genes, important in diabetes mellitus and atherosclerosis, would be associated with extent of CAD in patients with diabetes mellitus. Methods and Results— We genotyped 1043 patients (702 white, 175 blacks) from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) genetic cohort for 3351 variants in 223 PPAR pathway genes using a custom targeted-genotyping array. Angiographic end points were determined by a core laboratory. In whites, a single variant (rs1503298) in TLL1 was significantly ( P =5.5×10 −6 ) associated with extent of CAD, defined as number of lesions with percent diameter stenosis ≥20%, after stringent Bonferroni correction for all 3351 single nucleotide polymorphisms. This association was validated in the diabetic subgroups of 2 independent cohorts, the Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) post–myocardial infarction registry and the prospective Family Heart Study (FHS) of individuals at risk for CAD. TLL1 rs1503298 was also significantly associated with extent of severe CAD (≥70% diameter stenosis; P =3.7×10 −2 ) and myocardial jeopardy index ( P =8.7×10 −4 ). In general linear regression modeling, TLL1 rs1503298 explained more variance of extent of CAD than the previously determined clinical factors. Conclusions— We identified a variant in a single PPAR pathway gene, TLL1 , that is associated with the extent of CAD independently of clinical predictors, specifically in patients with type 2 diabetes mellitus and CAD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00006305.