TransRadial Education and Therapeutics (TREAT): shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention: a report from the Cardiac Safety Research Consortium.

Percutaneous coronary intervention (PCI) is an integral part of the treatment of coronary artery disease. The most common complication of PCI, bleeding, typically occurs at the vascular access site and is associated with short-term and long-term morbidity and mortality. Periprocedural bleeding also represents the primary safety concern of concomitant antithrombotic therapies essential for PCI success. Use of radial access for PCI reduces procedural bleeding and hence may change the risk profile and net clinical benefit of these drugs. This new drug-device safety interaction creates opportunities to advance the safe and effective use of antithrombotic agents during PCI. In June 2010 and March 2011, leaders from government, academia, professional societies, device manufacturing, and pharmaceutical industries convened for 2 think tank meetings. Titled TREAT I and II, these forums examined approaches to improve the overall safety of PCI by optimizing strategies for antithrombotic drug use and radial artery access. This article summarizes the content and proceedings of these sessions.

Association between endoscopic vs open vein-graft harvesting and mortality, wound complications, and cardiovascular events in patients undergoing CABG surgery.

CONTEXT: The safety and durability of endoscopic vein graft harvest in coronary artery bypass graft (CABG) surgery has recently been called into question. OBJECTIVE: To compare the long-term outcomes of endoscopic vs open vein-graft harvesting for Medicare patients undergoing CABG surgery in the United States. DESIGN, SETTING, AND PATIENTS: An observational study of 235,394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median 3-year follow-up) through December 31, 2008. MAIN OUTCOME MEASURES: All-cause mortality. Secondary outcome measures included wound complications and the composite of death, myocardial infarction, and revascularization. RESULTS: Based on Medicare Part B coding, 52% of patients received endoscopic vein-graft harvesting during CABG surgery. After propensity score adjustment for clinical characteristics, there were no significant differences between long-term mortality rates (13.2% [12,429 events] vs 13.4% [13,096 events]) and the composite of death, myocardial infarction, and revascularization (19.5% [18,419 events] vs 19.7% [19,232 events]). Time-to-event analysis for those patients receiving endoscopic vs open vein-graft harvesting revealed adjusted hazard ratios [HRs] of 1.00 (95% CI, 0.97-1.04) for mortality and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0% [3654/122,899 events] vs 3.6% [4047/112,495 events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001). CONCLUSION: Among patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting compared with open vein-graft harvesting was not associated with increased mortality.

Causes of late mortality after endovascular and open surgical repair of infrarenal abdominal aortic aneurysms.

INTRODUCTION: Several reports suggest unexpectedly high rates of late abdominal aortic aneurysm (AAA) rupture occur after endovascular AAA repair (EVAR). However, a population-based study examining causes of late death after EVAR vs open surgical repair has not been performed. METHODS: We performed a retrospective cohort study of patients undergoing infrarenal AAA repair using information from the Medicare inpatient hospital discharge records (MedPAR files), physician claim files (Part B files, 20% sample), and Medicare Denominator Files for the years 2001 to 2004. Using the Social Security Death Index, we identified all "late" deaths, defined as deaths occurring >30 days and after hospital discharge. We used the National Death Index to identify cause of death information; in particular, those deaths that were likely caused by late rupture. We compared causes of late death and survival between EVAR and open repair using Wilcoxon log-rank and rank-sum tests. RESULTS: Between 2001 and 2004, 13,971 patients underwent AAA repair (6119 EVAR, 7852 open repair). After a mean follow-up of 1.6 years in the EVAR cohort and 1.9 years in the open cohort, mortality rates were similar across repair type (15.4% EVAR, 15.9% open repair), with an adjusted odds ratio for death after open repair of 0.98 (95% confidence interval, 0.90-1.07). Of the 2194 documented deaths, 523 occurred before discharge or 30 days and after hospital discharge. Cause of death information for the 1671 late deaths was available from the National Death Index for 1515 (91%). The 15 most common codes for causes of late death were dominated by cardiac disease (atherosclerotic heart disease, acute myocardial infarction) and pulmonary disease (lung cancer, respiratory failure). Causes of late death with specific mention of aneurysm were identified in 37 patients (2.4% of all deaths), but this event was not more common in EVAR or open repair (15 [0.3%] in the EVAR group, 22 [0.3%], in the open repair group; P = .71). CONCLUSIONS: Late deaths from aneurysm rupture after EVAR or open repair appear to be relatively infrequent and similarly distributed across procedure type. Our results emphasize that the effectiveness of EVAR is comparable to open AAA repair in preventing aneurysm-related death.

The public health impact of the MiniMed Continuous Glucose Monitoring System (CGMS)-an assessment of the literature.

The Medtronic MiniMed (Northridge, CA) Continuous Glucose Monitoring System (CGMS) was approved by the U. S. Food and Drug Administration in 1999, for the continuous tracking of glucose concentration. The rationale for the use of this device is that frequent glucose measurements allow a more precise understanding of daily glucose fluctuations, without the inconvenience of frequent needle sticks. A review of the medical literature was undertaken to assess the public health impact of this device. Glucose readings from the MiniMed CGMS were found to correlate well with blood glucose (r = 0.73-0.92) and with hemoglobin A(1c) (HBA(1c)) (r = 0.53-0.59). Most important from a public health standpoint is the ability of the MiniMed device to detect episodes of asymptomatic hypoglycemia, and to lower HBA(1c) (absolute decline of 0.3%), as compared with controls. If these findings hold, the use of the MiniMed CGMS could result in a substantial reduction of morbidity and mortality associated with diabetes. The limitations of this analysis, most importantly the paucity of controlled studies that assess the ability of this device to result in improved control of diabetes over long periods of time, are discussed.

Risk of local adverse events following cardiac catheterization by hemostasis device use and gender.

Hemostasis devices are primarily used to stop bleeding from the femoral artery catheterization site after cardiac diagnostic or interventional procedures. Studies assessing the effectiveness of hemostatic devices compared to manual compression have produced mixed results regarding the relative risk of serious adverse events, such as hemorrhage. This study assessed the relative risk of serious complications following the use of the two main types of hemostasis devices (as compared with manual compression), and assessed the relative rates of these complications by gender.

Sex-based differences in outcomes after percutaneous coronary intervention for acute myocardial infarction: a report from TRANSLATE-ACS.

BACKGROUND: Data regarding sex-based outcomes after percutaneous coronary intervention (PCI) for myocardial infarction are mixed. We sought to examine whether sex differences in outcomes exist in contemporary practice. METHODS AND RESULTS: We examined acute myocardial infarction patients undergoing PCI between April 2010 and October 2012 at 210 US hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study. Outcomes included 1-year risk of major adverse cardiac events and bleeding according to Global Utilization of Strategies To Open Occluded Arteries (GUSTO) and Bleeding Academic Research Consortium (BARC) definitions. Among 6218 patients, 27.5% (n=1712) were female. Compared with men, women were older, had more comorbidities, and had lower functional status. Use of multivessel PCI and drug-eluting stents was similar between sexes, while women received less prasugrel. Unadjusted cumulative incidence of 1-year major adverse cardiac events was higher for women than for men (15.7% versus 13.6%, P=0.02), but female sex was no longer associated with higher incidence of major adverse cardiac events after multivariable adjustment (hazard ratio 0.98, 95% CI 0.83 to 1.15). Female sex was associated with higher risks of post-PCI GUSTO bleeding (9.1% versus 5.7%, P<0.0001) and postdischarge BARC bleeding (39.6% versus 27.9%, P<0.0001). Differences persisted after adjustment (GUSTO: hazard ratio 1.32, 95% CI 1.06 to 1.64; BARC: incidence rate ratio 1.42, 95% CI 1.27 to 1.56). CONCLUSIONS: Female and male myocardial infarction patients undergoing PCI differ regarding demographic, clinical, and treatment profiles. These differences appear to explain the higher observed major adverse cardiac event rate but not higher adjusted bleeding risk for women versus men.

Bleeding and vascular complications at the femoral access site following percutaneous coronary intervention (PCI): an evaluation of hemostasis strategies.

BACKGROUND: Previous research found at least one vascular closure device (VCD) to be associated with excess vascular complications, compared to manual compression (MC) controls, following cardiac catheterization. Since that time, several more VCDs have been approved by the Food and Drug Administration (FDA). This research evaluates the safety profiles of current frequently used VCDs and other hemostasis strategies. METHODS: Of 1089 sites that submitted data to the CathPCI Registry from 2005 through the second quarter of 2009, a total of 1,819,611 percutaneous coronary intervention (PCI) procedures performed via femoral access site were analyzed. Assessed outcomes included bleeding, femoral artery occlusion, embolization, artery dissection, pseudoaneurysm, and arteriovenous fistula. Seven types of hemostasis strategy were evaluated for rate of "any bleeding or vascular complication" compared to MC controls, using hierarchical multiple logistic regression analysis, controlling for demographic factors, type of hemostasis, several indices of co-morbidity, and other potential confounding variables. Rates for different types of hemostasis strategy were plotted over time, using linear regression analysis. RESULTS: Four of the VCDs and hemostasis patches demonstrated significantly lower bleeding or vascular complication rates than MC controls: Angio-Seal (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.65-0.70); Perclose (OR, 0.54; CI, 0.51-0.57); StarClose (OR, 0.77; CI, 0.72-0.82); Boomerang Closure Wire (OR, 0.63; CI, 0.53-0.75); and hemostasis patches (OR, 0.70; CI, 0.67-0.74). All types of hemostasis strategy, including MC, exhibited reduced complication rates over time. All trends were statistically significant except one. CONCLUSIONS: This large, nationally representative observational study demonstrated better safety profiles for most of the frequently used VCDs, compared to MC controls.

Long-term outcomes after transmyocardial revascularization.

BACKGROUND: Two independent reports documented substantially higher operative mortality associated with transmyocardial revascularization (TMR) when used in isolation than that reported in the premarket clinical trials. To clarify the state of the art, this article assesses temporal trends in the use of TMR, short-term and long-term outcomes, and outcomes stratified by procedure type (TMR only and TMR + coronary artery bypass graft [CABG]) and by the 2 specific TMR devices. METHODS: The study population included all patients undergoing TMR in isolation or in combination with CABG at 435 cardiothoracic hospitals in the United States participating in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) from January 2000 through November 2006 (n = 15,386). Analysis of long-term outcomes was accomplished through linkage to Medicare claims data. Short-term and long-term (7 years) adverse outcomes were assessed and compared between the 2 TMR device types. RESULTS: The use of TMR in conjunction with CABG surgery is increasing. This study showed modest differences in short-term morbidity and mortality between the 2 devices. In combination with CABG, after risk adjustment, patients treated with the holmium:YAG laser (experienced a higher rate of operative mortality (3.5% vs 2.5%; adjusted hazard ratio 1.39, 95% confidence level 1.03 to 1.87) but no difference in the composite short-term rate of major morbidity or mortality, compared with the Heart Laser CO2 transmyocardial revascularization system (PLC Medical Systems, Inc, Milford, MA). However, there were no clinically meaningful differences in long-term results. CONCLUSIONS: Modest differences in short-term morbidity and mortality between the 2 devices suggest the usefulness of further research.

Aneurysm-related mortality rates in the US AneuRx clinical trial.

BACKGROUND: The AneuRx (Medtronic) stent graft was approved by the FDA in September 1999. The purpose of this study was to ascertain the aneurysm-related mortality rate of a subgroup of the patient cohort from Medtronic's investigational premarket study. STUDY DESIGN: There were 931 study subjects, from 19 medical centers, who were followed for an average of 3.48 years. Abdominal aortic aneurysm (AAA)-related mortality rates were examined, using death certificates and medical records. RESULTS: The 1-month postimplant death rate was 1.61%. Not counting deaths related to the initial implant, there was an increase in the rate of AAA-related mortality after 3 years, from an average of 0.18% in the first 3 years to an average of 1.39% in years 4 and 5. CONCLUSIONS: Mortality in patients implanted with an AneuRx graft (as determined in this study) probably exceeds that of open procedure patients (based on medical literature) at some point in time, likely within 4 years after implant.

Gender differences in the treatment of non-ST-segment elevation myocardial infarction.

BACKGROUND: Women are at greater risk for worse outcomes associated with acute coronary syndrome (ACS) than are men. One explanation may be that they tend to be treated less aggressively than men even when more aggressive treatment is warranted. The purpose of this analysis was to assess this issue. METHODS: We used the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation (CRUSADE) Quality Improvement Initiative registry, an observational data collection that began in November 2001, with retrospective data collection from January 2001 to December 2006. A total of 32,888 subjects met the inclusion/exclusion criteria for our study, based on strong biochemical evidence of myocardial infarction and acute onset of typical cardiac chest pain. We stratified subjects into 16 cells for coronary intervention, based on 4 age groups and 4 cardiac catheterization findings (insignificant, 1-vessel disease, 2-vessel disease, 3-vessel disease). We also stratified subjects into 20 cells for medical treatment, based on 4 age groups and 5 medical treatments. In each cell we compared the rate of coronary intervention (coronary artery bypass grafting or percutaneous coronary intervention) or medical treatment (glycoprotein IIb/IIIa inhibitors, aspirin, clopidogrel, beta-blocker, and statins) for men vs women. RESULTS: Men demonstrated significantly higher rates (P < 0.05) of coronary intervention in 7 of the 16 cells and 9 of the 20 medical treatment cells, compared to no cells in which women had statistically higher rates than men. CONCLUSION: These findings suggest that men are more likely than women to receive coronary intervention and to be medically treated when presenting with evidence of non-ST-segment myocardial infarction, controlled for age, cardiac catheterization findings, and biochemical evidence of myocardial infarction.

Gender differences in correlates of troponin assay in diagnosis of myocardial infarction.

Cardiac troponins are the most sensitive and specific biomarker for myocardial infarction (MI) diagnosis. If there is a gender bias in MI diagnosis, it could be reduced by more consistently applying objective diagnostic criteria to improve women's outcomes. This study set out to assess the accuracy and correlates of the cardiac troponin I (cTnI) assay in the diagnosis of non-ST-segment elevation MI, to determine how the assay accuracy and correlates vary by gender, and to explore the interaction between factors that may influence cTnI accuracy and affect gender differences in diagnosis. The data were obtained from the CHECKMATE study. It included 924 patients with possible myocardial ischemia excluding subjects with ST-segment elevation. The Dade-Behring Stratus CS STAT near-patient instrument (Dade Behring, Inc, Newark, Del) was used to measure cTnI. We assessed baseline troponin accuracy using a standard MI definition. There were 125 subjects with a definite MI diagnosis. Baseline troponin was 44% sensitive and 97% specific in predicting MI, with no significant gender differences. In contrast, other positive cardiac markers, namely rising or falling creatine-kinase MB fraction and positive electrocardiogram, occurred more frequently in men. Sensitivity (SE) of baseline troponin was higher in subjects where baseline troponin was obtained longer than 2 hours after the chest pain onset. The study did not observe a significant difference in the assay SE or specificity by gender. This observation, plus the fact that other positive cardiac markers occurred more frequently in men, suggest the troponin test may help to improve the diagnosis of MI in women.

Risk of local adverse events by gender following cardiac catheterization.

PURPOSE: To assess the reason for the relative high risk of local complications for women following cardiac catheterization by evaluating the associations between gender, sheath size, and local adverse outcomes following cardiac catheterization. METHODS: The data used in this study were obtained from a portion of the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR), which included 13 878 patients who underwent cardiac catheterization at one of 59 participating cardiac catheterization institutions throughout the United States during late 2003. Rates of serious local vascular adverse events were calculated by gender following cardiac catheterization, by type of vascular hemostasis used, stratified by arterial sheath size. RESULTS: Serious local vascular events were reported in 3.54% of patients, most commonly hematoma (2.00%). The relative risk for women of any vascular complication was 1.40 [95%CI = 1.17, 1.67, p = 0.0002]. A statistically significant relative risk for woman was evident when collagen plug devices or manual compression alone were used as the first method for hemostasis. The rate of vascular complications increased progressively with increasing sheath size, more so in women than in men. CONCLUSIONS: High relative risk for women of local vascular complications following cardiac catheterization was demonstrated with use of manual compression, as well as with collagen plug devices to control femoral artery bleeding. Large sheath size is associated with both a relatively high absolute risk and a high relative risk for women. Knowledge of this information should be considered by interventional cardiologists in making decisions on how to achieve hemostasis following cardiac catheterization.

Risk of local adverse events following cardiac catheterization by hemostasis device use - phase II.

OBJECTIVES: To assess the relative risks of serious local adverse events following cardiac catheterization by type of hemostasis device (versus manual compression controls) and gender. BACKGROUND: Reports to the FDA (U.S. Food and Drug Administration) of local vascular complications associated with the use of hemostasis devices following cardiac catheterization and resulting in serious injuries, raised concerns about the safety of these devices. Review of the medical literature also posed cause for concern. METHODS: Data were obtained from the American College of Cardiology-National Cardiovascular Data Registry, modified to suit the needs of this research. It included information from 59 institutions and 13,878 cardiac catheterizations performed during the last quarter of 2003. Multiple logistic regression, using 10 different outcomes, was used to assess the risk associated with type of device and gender, while controlling for demographic and physiologic variables, type of procedure, and several indices of comorbidity. RESULTS: Serious adverse events were reported in 3.37% of patients, the most common being bleeding with hematoma (2.00%). The adjusted odds ratio for women (compared to men) was 1.73 for any vascular complication. Only one hemostasis device, VasoSeal, demonstrated a high risk of any vascular complication compared to manual compression controls (OR = 2.38 [1.47-3.85; p = 0.0004]). This risk was mainly associated with diagnostic cardiac catheterization (OR = 3.36). CONCLUSIONS: VasoSeal appears to pose a greater risk for serious local vascular complications following cardiac catheterization than either manual compression controls or other hemostasis devices. Women have almost twice the risk of men for most local complications.

Relative risks of reported serious injury and death associated with hemostasis devices by gender.

PURPOSE: To assess relative risks by gender of reported serious injuries and deaths associated with the use of hemostasis devices, stratified by year of report, type of injury, and type of device. METHODS: Reports from the Food and Drug Administration's Medical Device Reporting system and National Center for Health Statistics data on use of cardiac catheterization were used to estimate relative risks of reported serious injuries and deaths by gender. RESULTS: Estimated risks of reported serious injuries and deaths associated with hemostasis devices were two to three times greater in females than in males for hemorrhage and hematoma (p < 0.0001), but there was no significant difference in risks by gender for infection. CONCLUSIONS: Cardiac catheterization is sometimes associated with serious injuries and deaths. Among patients who receive hemostasis devices, the risk of these events are disproportionately greater in women.