Faculty Bibliography

OBJECTIVES/OBJECTIVE:This study examined a large registry to determine the frequency, predictors, and outcomes of native coronary artery versus bypass graft percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass graft surgery (CABG). BACKGROUND:The PCI target vessel and corresponding outcomes in prior CABG patients are poorly studied. METHODS:We analyzed the frequency and factors associated with native versus bypass graft PCI in prior CABG patients undergoing PCI between January 1, 2004, and June 30, 2009, in the National Cardiovascular Data Registry (NCDR) CathPCI Registry. Generalized estimating equations logistic regression modeling was used to generate independent variables associated with native versus bypass graft PCI and in-hospital mortality. RESULTS:During the study period, PCI in prior CABG patients represented 17.5% of the total PCI volume (300,902 of 1,721,046). The PCI target was a native coronary artery in 62.5% and a bypass graft in 37.5%: saphenous vein graft (SVG) (104,678 [34.9%]), arterial graft (7,517 [2.5%]), or both arterial graft and SVG (718 [0.2%]). Compared with patients undergoing native coronary artery PCI, those undergoing bypass graft PCI had higher-risk characteristics and more procedural complications. On multivariable analysis, several parameters (including graft stenosis and longer interval from CABG) were associated with performing native coronary PCI, and bypass graft PCI was associated with higher in-hospital mortality (adjusted odds ratio: 1.22, 95% confidence interval: 1.12 to 1.32). CONCLUSIONS:Most PCIs performed in prior CABG patients are done in native coronary artery lesions. Compared with native coronary PCI, bypass graft PCI is independently associated with higher in-hospital mortality.

Bleeding complications after coronary intervention are associated with prolonged hospitalization, increased hospital costs, patient dissatisfaction, morbidity, and 1-year mortality. Bleeding avoidance strategies is a term incorporating multiple modalities that aim to reduce bleeding and vascular complications after cardiovascular catheterization. Recent improvements in the rates of bleeding complications after invasive cardiovascular procedures suggest that the clinical community has successfully embraced specific strategies and improved patient care in this area. There remains controversy regarding the efficacy, safety, and/or practicality of 3 key bleeding avoidance strategies for cardiac catheterization and coronary intervention: procedural (radial artery approach, safezone arteriotomy), pharmacological (multiple agents), and technological (vascular closure devices) approaches to improved access. In this paper, we address areas of consensus with respect to selected modalities in order to define the role of each strategy in current practice. Furthermore, we focus on areas of controversy for selected modalities in order to define key areas warranting cautious clinical approaches and the need for future randomized clinical trials in this area.

OPINION STATEMENT/UNASSIGNED:Currently available data suggest that patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with stenting who do not continue oral anticoagulation are at increased risk for mortality and morbidity. In this patient population, therapy directed at reducing both thromboembolism (via oral anticoagulation) and stent thrombosis (via dual antiplatelet therapy) is necessary but is associated with an increased risk for bleeding. For patients with a high risk for thromboembolism based on published AF risk scores, the use of bare metal stents is recommended to minimize the duration of triple therapy. During the time period when triple therapy is used, the International Normalized Ratio (INR) should be maintained at the lower end of therapeutic range (2.0), and lower dose aspirin should be used. Finally, as newer oral anticoagulation agents such as dabigatran and rivaroxaban become available, further research will be required to determine their safety and efficacy in patients with AF undergoing PCI with stenting.

CONTEXT/BACKGROUND:Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. OBJECTIVE:To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. DESIGN, SETTING, AND PATIENTS/METHODS:A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60,000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. INTERVENTION/METHODS:Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. MAIN OUTCOME MEASURE/METHODS:Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 12 ± 2 weeks later (second CMR). RESULTS:In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n = 136; 15.8% LV mass [95% confidence interval {CI}, 13.3-18.2% LV mass] for the epoetin alfa group vs 15.0% LV mass [95% CI, 12.6-17.3% LV mass] for the placebo group; P = .67) or on the second CMR scan (n = 124; 10.6% LV mass [95% CI, 8.4-12.8% LV mass] vs 10.4% LV mass [95% CI, 8.5-12.3% LV mass], respectively; P = .89). In a prespecified analysis of patients aged 70 years or older (n = 21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (P = .03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P = .04). CONCLUSIONS:In patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses raised concerns about an increase in infarct size among older patients. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov Identifier: NCT00378352.

BACKGROUND:Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. METHODS:The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. FINDINGS/RESULTS:Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13-0·71; p=0·006). INTERPRETATION/CONCLUSIONS:Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. FUNDING/BACKGROUND:Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

The aim of the present study was to analyze the effect of drug exposure patterns of clopidogrel and proton pump inhibitors (PPIs) on the clinical outcomes after percutaneous coronary intervention (PCI). Previous analyses predominantly included discharge medications and did not explore the effect of the drug exposure patterns. We analyzed all-cause death, nonfatal myocardial infarction, repeat revascularization, and major adverse cardiovascular events (MACE) in a cohort of 23,200 post-PCI patients (January 2003 to December 2008) using a multivariate adjusted Cox model and propensity-matched case-control analysis. The adjusted hazard ratio for MACE on PPI according to the exposure patterns of clopidogrel after PCI for 6 years was 1.24 (95% confidence interval [CI] 1.11 to 1.38) and 1.12 (95% CI 1.03 to 1.22) for "continuous" (consistent clopidogrel with or without PPIs) and "switched" (clopidogrel with or without varying PPIs) respectively. However, the propensity score adjusted odds ratios for MACE on PPI use was 0.97 (95% CI 0.65 to 1.44) for "continuous" and 1.04 (95% CI 0.87 to 1.25) for "switched." Moreover, in the first year after PCI, the use of "rescue" (≤30 days before MACE) nitroglycerin was greater in the patients taking clopidogrel and PPIs than in those taking clopidogrel alone, as was the overall use of rescue PPIs (p <0.001). In conclusion, PPI use in clopidogrel-treated post-PCI patients was not associated with an increased risk of MACE after controlling for the confounding effect of PPI use with propensity matching. A potential for the misdiagnosis of angina symptoms and rescue use of nitroglycerin and PPIs in post-PCI patients exists, a finding that might have confounded previous observational analyses.

BACKGROUND: In the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) study, patients assigned enoxaparin or unfractionated heparin (UFH) were treated with alternative anticoagulant therapy after randomization at physician discretion, a practice made possible because the trial was open label. Using SYNERGY as an example, we demonstrate the difficulty of evaluating the effect of postrandomization events in clinical trials and discuss possible methodology. METHODS AND RESULTS: Patients with and without postrandomization crossovers were characterized and event rates analyzed. Statistical modeling was performed using inverse probability weighting and landmark analyses to evaluate the potential impact of postrandomization crossovers on event rates and treatment effect. Of 9978 SYNERGY patients, 9613 (96.3%) received at least 1 dose of randomized therapy and are included in these analyses. Of these, 740 (7.7%; 554 enoxaparin; 186 UFH) had postrandomization crossover. Crossover patients had higher unadjusted rates of 30-day death/myocardial infarction (MI) (18.9% versus 14.0%), thrombolysis in MI (TIMI) bleeding (16.9% versus 7.6%), Global Use of Strategies to Open Occluded Coronary Arteries bleeding (4.5% versus 2.3%), and transfusions (32.3% versus 15.2%). Adjustment for timing of crossover relative to the events attenuated the difference noted in death/MI but accentuated the association with TIMI bleeding. After adjustment using the inverse probability weighting technique, only a modest difference in the absolute treatment effect was observed between enoxaparin and UFH on death/MI (0.6% [unadjusted] versus 0.8% [adjusted]) and TIMI major bleeding (1.5% [unadjusted] versus 1.0% [adjusted]). The landmark analysis indicated a significant association between crossover from enoxaparin to UFH and TIMI bleeding but not in the other direction, and no crossover association was found in death/MI. CONCLUSIONS: Postrandomization events in clinical trials are accompanied by substantial confounders that require careful consideration. In SYNERGY, postrandomization crossovers occurred in nearly 10% of patients, abetted by the open-label trial design. These patients had increased incidence of bleeding and death/MI, but after adjustment using several modeling techniques, only a modest impact of postrandomization crossovers on treatment effect was observed. The usual methods of analyzing end points cannot adequately address biases in changing treatment in these patients. The potential biases of membership in a postrandomization subgroup, as well as the methods used to account for the biases, should be considered when weighing the strength of results. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00043784