Faculty Bibliography

Despite increasing use of the transradial approach (TRA) for coronary angiography, TRA failure and subsequent access site crossover remain a barrier to TRA adoption. The aim of this study was to elucidate patient and procedural characteristics associated with TRA to transfemoral approach (TFA) crossover and examine TRA to TFA crossover by operator experience over time. This retrospective analysis identified 1,600 patients who underwent coronary angiography with possible percutaneous coronary intervention through TRA by operators with varied TRA experience in an urban tertiary care center from October 2010 to August 2013. Univariate and multivariable logistic regression were used to identify independent predictors of access site crossover, from TRA to TFA, and strength of association is presented as odds ratio (OR, 95% confidence interval [CI]). Access site crossover was noted in 166 patients (10.4%). Multivariable predictors of access site crossover included age >75 years (OR 1.90, 95% CI 1.23 to 2.91, p = 0.004) and operator experience (OR 2.98, 95% CI 1.96 to 4.52, p <0.0001). Less experienced operators (5 years TRA experience) had no significant change in proportion of access site crossover over time (quartile 1: 2.8%, quartile 2: 6.4%, quartile 3: 5.6%, quartile 4: 5.8%, p = 0.54). In conclusion, rate of access site crossover in the contemporary era is relatively low and can be mitigated with operator experience.

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association guidelines for patients with ST-segment-elevation myocardial infarction gives a class III indication for nonculprit artery percutaneous coronary intervention at the time of primary percutaneous coronary intervention, driven by data from observational studies. However, more recent trials suggest otherwise. METHODS AND RESULTS: We conducted PUBMED, EMBASE, and CENTRAL searches for randomized trials comparing complete versus culprit-only revascularization in patients with ST-segment-elevation myocardial infarction. Efficacy outcomes were major adverse cardiovascular events, as well as death, cardiovascular death, myocardial infarction, and repeat revascularization. Safety outcomes were contrast-induced nephropathy, contrast volume used, and procedure time. Five trials with 1165 patients fulfilled the inclusion criteria. Complete revascularization (68% during index percutaneous coronary intervention) was associated with significant reduction in major adverse cardiovascular events (rate ratio =0.48; 95% confidence interval =0.37-0.61), death (rate ratio =0.60; 95% confidence interval =0.38-0.97), cardiovascular death (rate ratio =0.38, 95% confidence interval =0.20-0.73), and repeat revascularization (rate ratio =0.42; 95% confidence interval =0.31-0.57) when compared with culprit-only revascularization. However, trial sequential analyses (similar to interim analysis of a randomized trial) powered for a 25% relative reduction showed firm evidence (cumulative z-curve crossed the monitoring boundary) only for major adverse cardiovascular events driven by a decrease in repeat revascularization with no firm evidence for reduction in death and myocardial infarction. Moreover, there was a significant increase in contrast volume use (mean difference 85.12 [70.41-83.00] ml) and procedure time (mean difference 16.42 [13.22-19.63] mins) with complete revascularization without increase in contrast-induced nephropathy. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, immediate or staged complete revascularization results in significant reduction in major adverse cardiovascular events driven largely by reduction in repeat revascularization with no firm evidence for the reduction in death or myocardial infarction when compared with culprit-only revascularization.

BACKGROUND: Studies demonstrate that lowering low-density lipoprotein cholesterol (LDL-C) using a statin is associated with significant reduction in cardiovascular events. Whether visit-to-visit variability in LDL-C levels affects cardiovascular outcomes is unknown. OBJECTIVES: This study sought to evaluate the role of visit-to-visit variability in LDL-C levels on cardiovascular outcomes. METHODS: We evaluated patients with coronary artery disease and LDL-C <130 mg/dl enrolled in the TNT (Treating to New Targets) trial, randomly assigned to receive atorvastatin 80 mg/day versus 10 mg/day and with at least one post-baseline measurement of LDL-C. Visit-to-visit LDL-C variability was evaluated from 3 months into random assignment through the use of various measurements of LDL-C variability: SD, average successive variability (ASV), coefficient of variation, and variation independent of mean, with the first 2 measurements used as the primary measurements. Primary outcome was any coronary event, and secondary outcomes were any cardiovascular event, death, myocardial infarction, or stroke. RESULTS: Among 9,572 patients, SD and ASV were significantly lower with atorvastatin 80 mg/day versus 10 mg/day (SD: 12.03 +/- 9.70 vs. 12.52 +/- 7.43; p = 0.005; ASV: 12.84 +/- 10.48 vs. 13.76 +/- 8.69; p < 0.0001). In the adjusted model, each 1-SD increase in LDL-C variability (by ASV) increased the risk of any coronary event by 16% (hazard ratio [HR]: 1.16; 95% confidence interval [CI]: 1.10 to 1.23; p < 0.0001), any cardiovascular event by 11% (HR: 1.11; 95% CI: 1.07 to 1.15; p < 0.0001), death by 23% (HR: 1.23; 95% CI: 1.14 to 1.34; p < 0.0001), myocardial infarction by 10% (HR: 1.10; 95% CI: 1.02 to 1.19; p = 0.02), and stroke by 17% (HR: 1.17; 95% CI: 1.04 to 1.31; p = 0.01), independent of treatment effect and achieved LDL-C levels. Results were largely consistent when adjusted for medication adherence. CONCLUSIONS: In subjects with coronary artery disease, visit-to-visit LDL-C variability is an independent predictor of cardiovascular events.

BACKGROUND: Cross-sectional studies have shown associations between arsenic exposure and prevalence of high BP; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking. METHOD: We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every two years after baseline. Mixed effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with blood pressure annual change during follow-up (median, 6.7 years). RESULT: In the HEALS population, the median water arsenic concentration at baseline was 62 microg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in SBP compared with those in the reference group (beta=0.48 mmHg/year; 95% CI: 0.35-0.61, and beta=0.43 mmHg/year; 95% CI: 0.29-0.56) for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in DBP (beta=0.39 mmHg/year; 95% CI: 0.30, 0.49, and beta=0.45 mmHg/year; 95% CI: 0.36, 0.55) for water arsenic and urinary creatinine-adjusted arsenic, respectively) compared with those in the lowest quartile. CONCLUSION: Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease.

The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or dual therapy (DT) with OAC and clopidogrel. Major bleeding was the primary end point, whereas all-cause death, myocardial infarction (MI), stent thrombosis, and stroke were secondary ones. Results were reported for all studies and separately for those deriving from randomized controlled trials or multivariate analysis. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with TT. DAPT offered a significant reduction of major bleeding at 1 year for overall studies and for the subset of observational works providing adjusted data (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.39 to 0.68, I2 60% and OR 0.36, 95% CI 0.28 to 0.46) compared to TT. No increased risk of major adverse cardiac events (MACE: death, MI, stroke, and stent thrombosis) was reported (OR 0.71, 95% CI 0.46 to 1.08), although not deriving from randomized controlled trials or multivariate analysis. Six studies tested OAC and clopidogrel (1,263 patients) versus OAC, aspirin, and clopidogrel (3,055 patients) with a significant reduction of bleeding (OR 0.79, 95% CI 0.64 to 0.98), without affecting rates of death, MI, stroke, and stent thrombosis (OR 0.90, 95% CI 0.69 to 1.23) also when including clinical data from randomized controlled trials or multivariate analysis. In conclusion, compared to TT, both aspirin and clopidogrel and clopidogrel and OAC reduce bleeding. No difference in major adverse cardiac events is present for clopidogrel and OAC, whereas only low-grade evidence is present for aspirin and clopidogrel.

OPINION STATEMENT: The optimal revascularization strategy in patients with diabetes is controversial. The Bypass Angioplasty Revascularization Investigation (BARI) trial, done more than a decade ago, suggested a mortality benefit of coronary artery bypass graft surgery (CABG) when compared with percutaneous coronary intervention (PCI) (with plain old balloon angioplasty) in the subgroup of patients with diabetes. In addition, several observational studies and meta-analyses similarly suggest a benefit of CABG over PCI in patients with diabetes. However, most of these studies compared CABG with PCI using balloon angioplasty, bare metal stents, or first-generation drug-eluting stents. In this review, we critically examine the data for optimal revascularization strategy in patients with diabetes and ask the question whether the currently available data from randomized trials that used outdated stents are applicable to current day practice.

Background Results of trials and registry studies have shown lower long-term mortality after coronary-artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI) among patients with multivessel disease. These previous analyses did not evaluate PCI with second-generation drug-eluting stents. Methods In an observational registry study, we compared the outcomes in patients with multivessel disease who underwent CABG with the outcomes in those who underwent PCI with the use of everolimus-eluting stents. The primary outcome was all-cause mortality. Secondary outcomes were the rates of myocardial infarction, stroke, and repeat revascularization. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results Among 34,819 eligible patients, 9223 patients who underwent PCI with everolimus-eluting stents and 9223 who underwent CABG had similar propensity scores and were included in the analyses. At a mean follow-up of 2.9 years, PCI with everolimus-eluting stents, as compared with CABG, was associated with a similar risk of death (3.1% per year and 2.9% per year, respectively; hazard ratio, 1.04; 95% confidence interval [CI], 0.93 to 1.17; P=0.50), higher risks of myocardial infarction (1.9% per year vs. 1.1% per year; hazard ratio, 1.51; 95% CI, 1.29 to 1.77; P<0.001) and repeat revascularization (7.2% per year vs. 3.1% per year; hazard ratio, 2.35; 95% CI, 2.14 to 2.58; P<0.001), and a lower risk of stroke (0.7% per year vs. 1.0% per year; hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). The higher risk of myocardial infarction with PCI than with CABG was not significant among patients with complete revascularization but was significant among those with incomplete revascularization (P=0.02 for interaction). Conclusions In a contemporary clinical-practice registry study, the risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG. PCI was associated with a higher risk of myocardial infarction (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke. (Funded by Abbott Vascular.).

Outcomes of percutaneous coronary intervention (PCI) versus medical therapy (MT) in the management of stable ischemic heart disease (SIHD) remain controversial, with some but not all studies showing improved results in patients with ischemia. We sought to elucidate whether PCI improves mortality compared to MT in patients with objective evidence of ischemia (assessed using noninvasive imaging or its invasive equivalent). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PCI to MT in patients with SIHD. To maintain a high degree of specificity for ischemia, studies were only included if ischemia was defined on the basis of noninvasive stress imaging or abnormal fractional flow reserve. The primary outcome was all-cause mortality. We identified 3 RCTs (Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction II, Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2, and a substudy of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial) enrolling a total of 1,557 patients followed for an average of 3.0 years. When compared with MT in this population of patients with objective ischemia, PCI was associated with lower mortality (hazard ratio 0.52, 95% confidence interval 0.30 to 0.92, p = 0.02). There was no evidence of study heterogeneity or bias among included trials. In this meta-analysis of published RCTs, PCI was shown to have a mortality benefit over MT in patients with SIHD and objective assessment of ischemia using noninvasive imaging or its invasive equivalent. In conclusion, this study provides insight into the management of a higher-risk SIHD population that is the focus of the ongoing International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial.

The recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is the first study to demonstrate a significant benefit of another medication (ezetimibe) on top of statin therapy in patients who have recently experienced an acute coronary syndrome. Despite the fact that ezetimibe lead to positive results on the primary endpoint, the clinical benefit translated to real-life practice is only modest at best. However, this is the first major trial to demonstrate a significant benefit of a lipid medication in addition to statins. We explore the strengths and weaknesses of IMPROVE-IT in the context of current day acute coronary syndrome practice, where high dose statins are now widely prescribed.