Search

Introduction: Transfemoral access (TFA) is widely used for coronary angiography and percutaneous coronary intervention (PCI). The influence of operator age, gender, experience, and procedural volume on performance of femoral arterial access has not been studied., Methods: A survey instrument was developed and distributed via e-mail from professional societies to interventional cardiologists worldwide from March to December 2016., Results: A total of 988 physicians from 88 countries responded to the survey. TFA is the preferred approach for patients with cardiogenic shock, left main or bifurcation PCI, and procedures with mechanical circulatory support. Older (<50years: 56.4%; ≥50years: 66.8%, p<0.0039) and high PCI volume operators (<100 PCI: 57.3%; 100-299 PCI: 58.7%; ≥300 PCI: 64.3%, p<0.134) preferred palpation only without imaging (fluoroscopy or ultrasound (US)) for TFA. Most respondents preferred not to use micropuncture needle to puncture the femoral artery. Older (≥50years: 64.4%; <50years: 71.5%, p<0.04) and high PCI volume operators (≥300 PCI: 64.1%; 100-299 PCI: 72.6%; <100 PCI: 67.9%, p<0.072) tended not to perform femoral angiography (FA). Of those performing FA, the majority opted to do it at the end of the procedure., Conclusion: Despite best practice guideline recommendations, older and high PCI volume interventional cardiologists prefer not to use imaging for femoral access or perform femoral angiography during TF procedures. These data highlight opportunities to further reduce TFA complications., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents., (Copyright © 2018. Published by Elsevier Inc.)

Background: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration., Methods: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome., Results: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41)., Conclusions: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in patients undergoing early percutaneous coronary intervention (PCI) after fibrinolytic therapy is unknown. From May 2014 to August 2016, 212 patients undergoing PCI within 24 h of Tenecteplase (TNK), Aspirin, and Clopidogrel for ST-elevated myocardial infarction (STEMI) were randomized at four Canadian sites to receive additional Clopidogrel or Ticagrelor initiated prior to PCI. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline), at 4 and 24 h post PCI, and follow-up appointment. A mixed-model analysis with time as the repeated measure and drug as the between-subjects factor was calculated using 2 separate 1 × 4 ANOVAs, with students t-tests used to compare drugs within each time point. Complete clinical follow-up data (median 115.0 days; IQR 80.3-168.8) was available in 50 patients (23.6%) randomized to either Clopidogrel (n = 23) or Ticagrelor (n = 27). Analyses revealed significant decreases in PRU from baseline to 4 h (261.4 vs. 71.7; Mdiff = - 189.7; p < 0.001) to 24 h (71.7 vs. 27.7; Mdiff = - 44.0; p < 0.001) to end of follow-up (27.7 vs.17.9; Mdiff = - 9.9. p = 0.016) for those randomized to Ticagrelor and significant decreases in PRU only from baseline to 4 h (271.3 vs. 200.8; Mdiff = - 70.5, p = < 0.001) in patients receiving Clopidogrel, and a significantly greater proportion of patients with adequate platelet inhibition (PRU < 208) on long-term follow-up (Clopidogrel, 82.6% vs. Ticagrelor, 100.0%; p = 0.038). Our results demonstrate that in patients undergoing PCI within 24 h of fibrinolysis for STEMI, Ticagrelor provides prolonged platelet inhibition compared with Clopidogrel.

Background: The safety and efficacy of drug eluting stents (DES) in the setting of ST elevation myocardial infarction (STEMI) is not well established., Methods: In the TOTAL trial, patients presenting with STEMI were randomized to routine thrombectomy versus PCI alone. In this post-hoc analysis, propensity matching was used to assess relative safety and efficacy according to type of stent used., Results: Each propensity-matched cohort included 2313 patients. The composite primary outcome of cardiovascular death, recurrent MI, cardiogenic shock or class IV heart failure within one year was lower in the DES group (HR 0.67; 95% CI 0.54 to 0.84, p=0.0004). Cardiovascular death (HR 0.61; 95% CI 0.43 to 0.86, p=0.005), recurrent MI (HR 0.51; 95% CI 0.35 to 0.75, p=0.0005), target vessel revascularization (HR 0.47; 95% CI 0.36 to 0.62, p<0.0001) and stent thrombosis (HR 0.60; 95% CI 0.40 to 0.89, p=0.01) were lower in the DES group. There was no difference in major bleeding between groups., Conclusions: In this observational analysis, the use of DES was associated with improvement in cardiovascular outcomes compared to the use of BMS. These results support the use of DES during primary PCI for STEMI., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to examine the current practice and use of transfemoral approach (TFA) for coronary angiography and intervention., Background: Wide variability exists in TFA techniques for coronary procedures., Methods: The authors developed a survey instrument that was distributed via e-mail lists from professional societies to interventional cardiologists from 88 countries between March and December 2016., Results: Of 987 operators, 18% were femoralists, 38% radialists, 42% both, and 2% neither. Access using femoral pulse palpation alone was preferred by 60% of operators, fluoroscopy guidance by 11%, and a combination of palpation, fluoroscopy, or ultrasound by 27%. Only 11% used micropuncture in >90% of their cases. Performing femoral angiography immediately after access was preferred by 23% and at the end of the procedure by 47%, and not done at all by 31% of operators. Hemostasis by manual compression was preferred by 50%, collagen plug vascular closure device by 31%, and suture-based vascular closure device by 11% of operators. Judkins left and right catheters were preferred for diagnostic angiography of the left (99%) and right (94%) coronary arteries. Extra backup curves (XB or EBU) were most commonly preferred for percutaneous coronary intervention of the left anterior descending (80%) and left circumflex (80%), whereas the Judkins right catheter was preferred for percutaneous coronary intervention of the right coronary artery (86%)., Conclusions: There is significant variability in preferences for femoral access technique. Even though recommended best practices advocate for fluoroscopic and ultrasound guidance, most operators use palpation alone. Femoral angiography is also not consistently used despite guideline recommendations. The lack of adoption of imaging guidance for vascular access deserves further investigation., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The efficacy and safety of pharmacoinvasive strategy following fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to renal function have not been established., Methods: Using patient-level data from 4 randomized controlled trials, we examined the efficacy and safety of pharmacoinvasive versus standard treatment after fibrinolysis for STEMI. Patients were stratified based on the estimated glomerular filtration rate (eGFR) on presentation (<60 mL/min/1.73 m 2 vs ≥60 mL/min/1.73 m 2 ). The primary outcome was the composite of death or reinfarction at 30 days., Results: Of 2,029 patients, 457 (23%) had an eGFR<60 mL/min/1.73 m 2 . Patients with eGFR<60 mL/min/1.73 m 2 were older and had higher Thrombolysis in Myocardial Infarction risk scores. Compared with patients with eGFR≥60 mL/min/1.73 m 2 , patients with renal dysfunction had higher rates of the primary outcome (5.3% vs 11.8%, respectively; P<.001). There was no significant heterogeneity in the treatment effect of pharmacoinvasive strategy on the primary outcome (P heterogeneity=.73) or the rate of death or reinfarction at 1 year (P heterogeneity=.64) in relation to eGFR. Patients with renal dysfunction had higher rates of in-hospital major bleeding compared with patients with eGFR ≥60 mL/min/1.73 m 2 (7.7% vs 4.3%, respectively; P=.004); however, there was no difference in bleeding events between treatment arms in the overall cohort or in relation to eGFR (P heterogeneity=.67)., Conclusions: Renal impairment is associated with increased rates of adverse events in STEMI patients treated with fibrinolysis. However, the safety and efficacy of pharmacoinvasive strategy are preserved in patients with renal impairment on presentation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI., Methods and Results: Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, P<.001) and at 24 hours (34.5±35.0 and 153.5±75.5, respectively, P<.001). The primary end point was observed in 87.8% (n=65) in the ticagrelor-treated patients compared to 57.6% (n=38) of clopidogrel-treated patients, P<.001., Conclusion: Fibrinolysis-treated STEMI patients who received clopidogrel and aspirin at the time of fibrinolysis and were undergoing early PCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, https://clinicaltrials.gov/ct2/show/NCT01930591)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cardiovascular disease encompasses coronary artery disease and valvular heart disease, and the prevalence of both increases with age. Over the past decade, the landscape of interventional cardiology has evolved to encompass a new set of percutaneous procedures outside the coronary tree, including transcatheter aortic valve implantation, transcatheter mitral valve repair, and left atrial appendage occlusion. These interventions have sparked a new discipline within interventional cardiology referred to as structural heart disease (SHD) intervention. The access to and numbers of such procedures performed in Canada is currently unknown. This "first of its kind" survey of structural interventions provides insight into the landscape of SHD intervention in Canada and the challenges faced by cardiologists to deliver this important care., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Once considered a childhood disease, the number of adults living with congenital heart disease (CHD) has now exceeded the number of pediatric patients. The landscape of percutaneous intervention for adult congenital heart disease (ACHD) has evolved over the past decade and has yet to be characterized in Canada. The aim of this study was to begin to understand the current infrastructure underlying ACHD interventions in Canada and to characterize the type and number of interventions being carried out across the country. A cross-sectional national survey was distributed by e-mail to all cardiac catheterization laboratory directors in 2015. All Canadian laboratories involved in ACHD interventions responded, encompassing 19 institutions spanning 69 cardiac catheterization laboratories. A total of 1451 percutaneous interventions were recorded. Nationwide, the most common simple ACHD interventions were for atrial septal defect and patent foramen ovale closures. The most common ACHD interventions of increased complexity were for coarctation stenting and transcatheter pulmonary valve implantation. There was a marked clustering of procedures in Ontario, Québec, British Columbia, and Alberta in keeping with Canada's population-density distribution. A total of 23 ACHD operators were identified, half of whom had ACHD-specific fellowship training. These data can be used as a starting point to inform the present state of affairs in the area and lay the groundwork for further work to assess resource allocation and human resource planning for the care of patients with ACHD in Canada., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: Our objective was to evaluate sex-differences in outcomes after trans-catheter aortic valve replacement (TAVR) in a population-based cohort from Ontario, Canada., Background: Prior studies comparing outcomes in men and women after TAVR have yielded divergent results. Some studies have suggested that women have better survival than men while others have not corroborated this finding., Methods: A retrospective observational cohort study was conducted using chart abstraction data on all TAVR procedures performed between 2007 and 2013 in Ontario, Canada. Patients who had emergency TAVR procedures were excluded. The primary outcome was all-cause mortality at 30-days and 1-year. Secondary outcomes included mortality at last follow-up, cause-specific, and all-cause hospital readmission. Inverse probability of treatment weighting (IPTW) using propensity score was used to adjust for baseline differences between men and women., Results: The final study cohort consisted of 453 women and 546 men with a mean follow-up of 3.5 years. Women were generally older and more frail but had less comorbid conditions. Women had lower unadjusted mean EuroScores (7% ± 5% vs 8% ± 7%; P = 0.008), but underwent significantly more trans-apical procedures (26.5% vs 19.2%; P = 0.006) than men. After IPTW, the groups were well balanced. Although mortality was numerically higher for women at 30-days (7.2% vs 5.4%), this was not statistically significant (P = 0.34). At 1-year, there was no difference in mortality (18.2% vs 19.2%; P = 0.85). There were no significant differences in all-cause readmission., Conclusion: In this population-based cohort including all patients undergoing TAVR, mortality or all-cause readmission were not significantly different between men and women. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Aims: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial., Methods and Results: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as ≥70%. Complete STR occurred pre-PCI in 12.8% (204/1,598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre-PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258)., Conclusions: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active.

Transcatheter aortic valve implantation (TAVI) is the treatment of choice for inoperable and high-risk patients with severe aortic stenosis. Our objectives were to elucidate potential differences in clinical outcomes and safety between balloon-expandable versus self-expandable transcatheter heart valves (THV). We performed a retrospective cohort study of all transfemoral TAVI procedures in Ontario, Canada, from 2007 to 2013. Patients were categorized into either balloon-expandable or self-expandable THV groups. The primary outcomes were 30-day and 1-year death, with secondary outcomes of all-cause readmission. Safety outcomes included bleeding, permanent pacemaker implantation, need for a second THV device, postprocedural paravalvular aortic regurgitation, stroke, vascular access complication, and intensive care unit length of stay. Inverse probability of treatment-weighted regression analyses using a propensity score were used to account for differences in baseline confounders. Our cohort consisted of 714 patients, of whom 397 received a self-expandable THV, whereas 317 had a balloon-expandable THV system. There were no differences in death or all-cause readmission. In terms of safety, the self-expandable group was associated with significantly higher rates of inhospital stroke (p value <0.05), need for a second THV device (5.3% vs 2.7%; p value = 0.013), and permanent pacemaker (22.6% vs 8.9%; p value <0.001), whereas the balloon-expandable group had more vascular access site complications (23.1% vs 16.7%; p value = 0.002). Thus, we found similar clinical outcomes of death or readmission for patients who underwent transfemoral TAVI with either balloon-expandable or self-expandable THV systems. However, there were important differences in their safety profiles., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Studies showing an advantage of transradial approach (TR) for coronary angiography and intervention (PCI) compared to the transfemoral approach (TF) predominantly included a younger population. Therefore, we conducted a meta-analysis of published studies to determine the efficacy of TR in the elderly population., Methods and Results: A comprehensive search identified 16 studies [3 randomized controlled studies, 13 observational] comprising 777,841 elderly patients undergoing PCI. TR was used in 99,201 patients and TF in 678,640 patients. The results from observational studies showed that TR was associated with a lower rate of vascular complications (0.4% vs. 0.8%, OR 0.36, 95% CI 0.30-0.44), stroke (0.3% vs. 0.4%, OR 0.81, 95% CI 0.66-1.0) and death (2.0% vs. 2.2%, OR 0.51, 95% CI 0.41-0.63). RCTs confirmed findings from observational studies for both significant reduction in vascular complications (2.7% vs. 7%, OR 0.37, 95% CI 0.23-0.60) and stroke (0.4% vs. 1.4%, OR 0.31, 95% CI 0.10-0.97) but showed no effect on mortality (3.3% vs. 2.8%, OR 1.20, 95% CI 0.69-2.09). However, among patients with ST elevation myocardial infarction (STEMI), TR was associated with a mortality benefit (5% vs. 7%, OR 0.48, 95% CI 0.25-0.90, p=0.02). Access site crossover rate was higher for TR compared to the TF approach (11% vs. 3%, p=0.0003) but there was no difference in contrast media use, procedure duration, fluoroscopy time and door to balloon time for STEMI., Conclusion: TR for PCI in the elderly is associated with a reduced risk of stroke, lower rate of vascular complications overall and a mortality benefit for patients presenting with STEMI. The access site cross rate for TR is higher compared to TF but remains acceptably low. TR should be the preferred strategy for PCI in the elderly to optimize clinical benefit in this high-risk group., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or everolimus-eluting stents) for reducing major adverse cardiac events (MACE)., Methods and Results: This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion. The primary efficacy outcome was the first occurrence of MACE defined as the composite of cardiac death, myocardial infarction, or coronary revascularization related to the target SVG during the duration of follow-up (minimum of 2 years). Secondary efficacy outcomes included MACE related to the target SVG lesion and overall MACE. A total of 125 patients (mean age 70±9 years, 87% men) were included, with a mean time from coronary artery bypass graft of 12±5 years. Sixty and 65 patients were allocated to the SVG-DES and SVG-MT groups, respectively. There were no events related to the target SVG at 30 days. After a median follow-up of 3.4 (interquartile range: 2.8-3.9) years, the MACE rate related to the target SVG was not significantly different in the 2 groups (SVG-DES: 15.0%, SVG-MT: 20.0%; hazard ratio, 0.65; 95% confidence interval, 0.23-1.53; P=0.33). There were no significant differences between groups in MACE related to the target SVG lesion (SVG-DES: 10.0%, SVG-MT: 16.9%; hazard ratio, 0.53; 95% confidence interval, 0.20-1.43; P=0.21) or global MACE (SVG-DES: 36.7%, SVG-MT: 44.6%; hazard ratio, 0.73; 95% confidence interval, 0.42-1.27; P=0.26)., Conclusions: Sealing intermediate nonobstructive SVG lesions with DES was safe but was not associated with a significant reduction of cardiac events at 3-year follow-up., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01223443., (© 2016 American Heart Association, Inc.)

Background: We examined whether the efficacy of an early invasive strategy after fibrinolysis in ST-segment elevation myocardial infarction (STEMI) differs in relation to the initial troponin status., Methods: In the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), patients with STEMI presenting to a non-percutaneous coronary intervention (PCI)-capable hospital who received fibrinolysis were randomized to either a pharmacoinvasive or standard strategy for subsequent angiography and PCI. In this post hoc subgroup analysis, we compared the efficacy of these strategies in relation to the initial troponin status at hospital presentation for the primary composite end point of mortality, reinfarction, recurrent ischemia, heart failure, and cardiogenic shock at 30 days. We assessed the heterogeneity of treatment effect with initial troponin status using the Breslow-Day test and tested for interaction after adjustment for baseline Global Registry of Acute Coronary Events (GRACE) risk score., Results: Among 1059 patients, those with abnormal initial troponin levels (n = 514 [48.5%]) were older with worse Killip class, had a longer time from symptom onset to fibrinolysis, and had higher GRACE and Thrombolysis In Myocardial Infarction risk scores. Patients with abnormal troponin levels had higher rates of the primary end point (17.5% vs 10.8%; P = 0.002) and cumulative mortality or reinfarction at 1 year (14.0% vs 8.1%; P = 0.003). In stratified analyses, pharmacoinvasive management reduced the primary end point only among patients with normal initial troponin status. However, there was no significant treatment heterogeneity (all P ≥ 0.10) and no interaction between initial troponin status and treatment assignment after adjusting for GRACE risk score., Conclusions: Patients with STEMI and abnormal initial troponin levels had worse short-term and long-term outcomes. Accounting for overall baseline risk with the GRACE risk score, troponin status did not modulate the efficacy of pharmacoinvasive management., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST elevation myocardial infarction (STEMI). However, only one-third of hospitals in the US have PCI availability 24/7. For non-PCI hospitals, transfer remains the optimal strategy. For expected delays of greater than 120 minutes, a pharmacoinvasive strategy is recommended. In patients with evidence of failed reperfusion or hemodynamic instability, immediate rescue PCI should be performed. All other patients should undergo routine cardiac catheterization and PCI within 24 hours after fibrinolysis. A pharmacoinvasive strategy is best implemented within an organized regional STEMI system with prospective standardized transfer protocols., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis., Methods: Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction., Results: 1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk., Conclusions: In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality., Summary: This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study., Background: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min)., Methods: The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST-segment elevation resolution, and clinical endpoints over the first 24 h., Results: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events., Conclusions: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580])., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction are at increased risk for adverse events. It is unclear if image guidance by optical coherence tomography (OCT) can improve outcomes in these patients. We compared OCT-guided versus angiography-guided primary PCI for ST-segment-elevation myocardial infarction among patients in the Thrombectomy Versus PCI Alone (TOTAL) trial., Methods and Results: Among 10 732 patients enrolled in the TOTAL trial, OCT was used for PCI guidance as a part of a prospective substudy in 214 patients. Using 2:1 propensity matching, we identified 428 patients in the trial who had PCI performed with angiography guidance alone. The primary outcome was a composite of cardiovascular death, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. Secondary outcomes included final in-stent angiographic minimum lumen diameter, procedure time, and contrast dose. The final in-stent angiographic minimum lumen diameter was 2.99±0.48 mm in the OCT-guided group versus 2.79±0.47 mm in the angiography-guided group (P<0.0001). OCT- and angiography-guided PCI had a median (interquartile range) procedure time of 58 (47, 71) minute versus 38 (28, 52) minute (P<0.0001) and total contrast dose of 239.7±81.1 mL versus 193.3±78.6 mL (P<0.0001). The primary outcome was observed in 7.5% of the OCT-guided group versus 9.8% of the angiography-guided group (hazard ratio, 0.76; 95% confidence interval, 0.43-1.34; P=0.34)., Conclusions: OCT-guided primary PCI for ST-segment-elevation myocardial infarction was associated with a larger final in-stent minimum lumen diameter. There was no significant difference in clinical outcomes at 1 year; however, the study was underpowered to detect a treatment effect., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01149044., (© 2016 American Heart Association, Inc.)

Background: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding., Methods: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions., Findings: 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002)., Interpretation: The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin., Funding: Regado Biosciences Inc., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice., Methods: The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044., Findings: Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015)., Interpretation: Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI., Funding: Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc., Competing Interests: Declaration of interests SSJ has received grants from Medtronic during the conduct of the study. JAC has received grants from the Canadian Institutes of Health Research and Medtronic during the conduct of the study, and grants from Medtronic outside the submitted work. RM has received personal fees from Medtronic during the conduct of the study. AG has received personal fees and advisory board fees from AstraZeneca, and grants, meeting support, and research grants from Medronic, outside the submitted work. PGS has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Medtronic, Vivus, Janssen, Orexigen, and Regado; grants and personal fees from Sanofi and Servier; and personal fees and non-financial support from The Medicines Company, outside the submitted work. RCW has received personal fees from Medtronic; grants from Abbott Vascular and Edwards Lifesciences, grants and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Jansen and BMS/Pfizer, outside the submitted work. SVR has received personal fees from Medtronic, outside the submitted work. SP has received personal fees from Medtronic, outside the submitted work. VD has received an institutional grant to conduct the trial from the TOTAL Coordinating Centre during the conduct of the study. All other coauthors declare no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Radial access for percutaneous coronary intervention is associated with lower rates of access site complications and bleeding. However, elderly patients have more complex vascular anatomy and radial access may be more challenging in this population. There remains uncertainty regarding the role of radial access in elderly patients undergoing cardiac catheterization., Methods and Results: The RIVAL trial randomized patients with acute coronary syndromes undergoing cardiac catheterization to radial versus femoral access. In this analysis, the rates of access site complications and access site cross-over were compared across different age groups. Among the 7,021 patients, 1035 (15%) were ≥75 years of age. Across all age categories, radial access was consistently associated with higher rates of access site cross over and lower rates of major access site complications, with no significant interaction between age and access site. Radial access was associated with lower rates of major vascular access site complications in patients ≥75 years of age (3.6% vs 6.6%; P = .03) and in patients <75 years of age (1.0% vs 3.2%; P < .001; P value for interaction = .2). The rates of access site crossover were higher with radial access among patients ≥75 (12.5% vs 2.6%; P < .001) and <75 (6.7% vs 1.9%; P < .001; P value for interaction = .9). There were no significant differences in the primary composite outcome (death, myocardial infarction, stroke or non coronary artery bypass graft major bleeding) or its individual components in either age group. In patients ≥75 years of age undergoing primary percutaneous coronary intervention, there was no significant difference in procedure time (120 vs 115 minutes; P = .3)., Conclusions: Consistent with the overall RIVAL trial population, elderly patients undergoing cardiac catheterization have lower rates of major bleeding or access site complications and higher rates of access site crossover with radial access compared to femoral access., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Randomised controlled trials have demonstrated improved outcomes with an early invasive strategy compared with routine care after fibrinolysis among patients with ST-elevation myocardial infarction. However, it remains uncertain whether specific patient subsets derive differential benefit from an early invasive strategy., Methods: Using patient-level data from seven randomised trials, we studied the relationship between treatment assignment (early invasive vs standard care) and adverse cardiovascular events. The outcomes assessed were death/reinfarction at 30 days and at 1 year, as well as death/reinfarction/recurrent ischaemia, major bleeding and stroke at 30 days. The analyses were conducted in strata (age, sex, diabetes, prior infarction, Killip class, anterior infarction and time from symptom onset to fibrinolysis) to assess for an interaction between the stratifying variable and treatment assigned., Results: There were 101 deaths and 115 recurrent infarctions at 30 days in 3010 patients. There were no strata where an invasive strategy conferred a differential treatment effect. With the exception of a marginally significant interaction between Killip class and treatment for death/reinfarction at 30 days and 1 year (p values for interaction 0.044 and 0.038, respectively), no interactions between the stratifying variables and treatment assignment were observed., Conclusions: Benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is similar across patient subgroups stratified by these clinical characteristics. Therefore, prediction of risk and benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is best achieved by global risk evaluation rather than specific patient characteristics., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims: Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone., Methods and Results: The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups., Conclusion: Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow., Competing Interests: T.S. reports grants and personal fees from St Jude Medical, during the conduct of the study; W.J.C. reports personal fees from AstraZeneca, Roche Canada, and Daiichi Sankyo, outside the submitted work; A.F. reports personal fees from Proctor for St Jude Medical, outside the submitted work; S.S.J. reports grants from Medtronic and St Jude, during the conduct of the study; V.K. reports grants, personal fees, and non-financial support from Medtronic, personal fees and non-financial support from Abbott Vascular, non-financial support from B. Braun, outside the submitted work., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Radial access is associated with less bleeding and vascular complications. However, it may delay reperfusion during primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction., Methods and Results: A provincial database prospectively collected clinical and procedural characteristics for all urgent percutaneous coronary intervention procedures performed between June 2010 and September 2011 in Ontario for ST-segment-elevation myocardial infarction, including time of arrival in the catheterization laboratory and time of first balloon inflation. After excluding patients with cardiogenic shock, with previous bypass surgery, or who received fibrinolysis, 2947 patients were included in the analysis. Propensity score matching was used to minimize difference in clinical characteristics between radial and femoral access procedures. Predictors of radial access included younger age and male sex. After propensity score matching, the median time from arrival in the cardiac catheterization laboratory to first balloon was 27 minutes (25th%-75th%, 21-34) for the femoral group and 30 minutes (25th%-75th %, 24-39) for the radial group (P<0.001). When hospitals were stratified based on the proportion of primary percutaneous coronary intervention cases that were performed using radial access, there was no difference in treatment times between radial and femoral access in the tercile of hospitals that used radial access most frequently. There were no significant differences in the rates of death or myocardial infarction at 30 days., Conclusions: This contemporary multicenter registry demonstrates that the time to first balloon inflation is slightly longer with radial access than with femoral access, although the 3 minute difference is unlikely to be clinically relevant. There is no difference in treatment times at hospitals that frequently use radial access for primary percutaneous coronary intervention. Short-term mortality and reinfarction rates are similar with radial and femoral access., (© 2015 American Heart Association, Inc.)

Background: The use of invasive coronary angiography in stable ischemic heart disease (IHD) varies widely., Objective: To validate the 2012 appropriate use criteria for diagnostic catheterization by examining the relationship between the appropriateness of cardiac catheterization in patients with suspected stable IHD and the proportion of patients with obstructive coronary artery disease (CAD) and subsequent revascularization., Design: Population-based, observational, multicenter cohort study., Setting: The Cardiac Care Network, a registry of all patients having elective angiography at 18 hospitals in Ontario, Canada, between 1 October 2008 and 30 September 2011., Patients: Persons without prior coronary revascularization or myocardial infarction who had angiography for suspected stable CAD., Measurements: Appropriateness scores were ascertained by using data collected at the time of the index angiography and were categorized as appropriate, inappropriate, or uncertain., Results: Among the final cohort of 48 336 patients, 58.2% of angiographic studies were classified as appropriate, 10.8% were classified as inappropriate, and 31.0% were classified as uncertain. Overall, 45.5% of patients had obstructive CAD. In patients with appropriate indications for angiography, 52.9% had obstructive CAD, with 40.0% undergoing revascularization. In those with inappropriate indications, 30.9% had obstructive CAD and 18.9% underwent revascularization; in those with uncertain indications, 36.7% had obstructive CAD and 25.9% had revascularization. Although more patients with appropriate indications had obstructive CAD and underwent revascularization (P < 0.001), a substantial proportion of those with inappropriate or uncertain indications had important coronary disease., Limitation: Data were not available on whether symptoms were atypical., Conclusion: Despite the association between appropriateness category and obstructive CAD, this study raises concerns about the ability of the appropriate use criteria to guide clinical decision making., Primary Funding Source: Canadian Institutes of Health Research.

Objectives: The purpose of this study was to determine the efficacy and safety of radial versus femoral access in women undergoing coronary angiography/intervention., Background: The risk of bleeding and vascular access site complications are higher in women than in men., Methods: In a pre-specified RIVAL (RadIal Vs femorAL access for coronary intervention) subgroup analysis, we compared outcomes in women (n=1,861) and men (n=5,160) randomized to radial versus femoral access., Results: Overall, women were at higher risk of major vascular complications compared with men (4.7% vs. 1.7%; p<0.0001). Major vascular complications were significantly reduced with radial access in women (3.1% vs. 6.1%; hazard ratio [HR]: 0.5; 95% confidence interval [CI]: 0.32 to 0.78; p=0.002) and in men (0.7% vs. 2.8%; HR: 0.27; 95% CI: 0.17 to 0.45; p<0.0001; interaction p=0.092). Crossover rates were higher with radial compared with femoral access in women (11.1% vs. 1.9%; HR: 5.88; p<0.0001) and men (6.3% vs. 1.9%; HR: 3.32; p<0.0001; interaction p=0.054). Percutaneous coronary intervention (PCI) success rates were similar irrespective of access site (women: HR: 1.05; p=0.471; men: HR: 1.00; p=0.888; interaction p=0.674), with no differences in PCI complications. In multivariable analyses, female sex was an independent predictor of major vascular complications (HR: 2.39; 95% CI: 1.76 to 3.25; p<0.0001). There were consistent findings for women and men, with no difference for the primary composite endpoint of death, myocardial infarction, stroke, and non-coronary artery bypass grafting bleeding (women: 3.9% vs. 5.0%; HR: 0.77; 95% CI: 0.50 to 1.19; men: 3.54% vs. 3.5%; HR: 1.00; 95% CI: 0.75 to -1.34; interaction p=0.325)., Conclusions: Women undergoing coronary angiography and PCI have a higher risk of vascular access site complications compared with men, and radial access is an effective method to reduce these complications., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results., Methods: We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days., Results: The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02)., Conclusions: In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Background: There is a paucity of data on the comparative effectiveness of percutaneous coronary intervention using contemporary drug-eluting stent (DES) compared with coronary artery bypass graft (CABG) surgery in patients with chronic kidney disease., Methods and Results: A population-based study was performed using the Cardiac Care Network, a provincial registry of all patients undergoing cardiac catheterization in Ontario, to evaluate patients treated with either percutaneous coronary intervention using DES or CABG between October 1, 2008, and September 30, 2011. Chronic kidney disease was defined as creatinine clearance <60 mL/min. A total of 1786 propensity-matched patients from 4006 patients with chronic kidney disease undergoing index revascularization for multivessel disease with either DES or isolated CABG (n=893 each group) were analyzed. Baseline and procedural characteristics between percutaneous coronary intervention and CABG groups were well-balanced, including urgent revascularization priority, diabetes mellitus, left ventricular function, and 3-vessel disease. The 1-, 2-, and 3-year Kaplan-Meier survival analyses in propensity-matched patients favored CABG (93.2% versus 89.3%; 86.6% versus 80.3%; 80.8% versus 71.5%, respectively; P<0.001). The CABG cohort had greater 1-, 2-, and 3-year freedom from major adverse cardiac and cerebrovascular events (89.4% versus 71.2%; 81.9% versus 60.5%; 75.2% versus 51.8%, respectively; P<0.001). Cox regression analysis identified DES use to be associated with greater hazard for late mortality (hazard ratio, 1.58; 95% confidence interval, 1.32-1.90) and major adverse cardiac and cerebrovascular events (2.62; 2.28-3.01; all P<0.001)., Conclusions: In this large provincial registry, CABG was associated with improved early and late clinical outcomes when compared with percutaneous coronary intervention using DES in patients with chronic kidney disease undergoing index revascularization., (© 2015 American Heart Association, Inc.)

Objectives: This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis., Background: The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain., Methods: Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models., Results: Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01)., Conclusions: Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A strategy of early transfer for coronary angiography and intervention is superior to a standard approach of delayed coronary angiography after fibrinolysis for ST-elevation myocardial infarction (STEMI). STEMI patients with lesions in noninfarct-related arteries have a worse prognosis compared with patients with single vessel disease. This study aimed to assess whether the benefits of an early invasive strategy differ in patients with single vessel and multivessel disease., Methods: The Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized STEMI patients receiving fibrinolysis to a strategy of early transfer and coronary angiography vs a standard approach. In this post hoc analysis, we stratified 992 patients into 2 groups according to the presence or absence of multivessel disease. We compared the 2 groups in terms of baseline characteristics, in-hospital management, and patient outcomes, and tested for treatment heterogeneity., Results: Multivessel disease was present in 369 (37%) patients. Patients with multivessel disease had a greater rate of the primary composite end point of in-hospital death, recurrence of infarction, recurrent ischemia, shock, or heart failure at 30 days (18.2% vs 10.8%; P < 0.001). An early invasive strategy was efficacious in both groups for the primary outcome. In multivariable analysis adjusting for Global Registry of Acute Coronary Events (GRACE) risk score, there was no significant treatment heterogeneity (all P interaction > 0.40) for the primary end point, or death/recurrence of infarction at 6 months and 1 year., Conclusions: Multivessel disease is present in a significant proportion of STEMI patients treated with fibrinolysis and is associated with worse outcomes. A strategy of early transfer and coronary intervention after fibrinolysis was beneficial regardless of the presence or absence of multivessel disease., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience (P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST-elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The efficacy of a routine invasive strategy early after fibrinolysis in relation to baseline risk status is unclear. We sought to characterize the interaction between patient risk and treatment with routine invasive strategy early after fibrinolysis for ST-segment elevation myocardial infarction., Methods: We pooled 2,974 patients from 7 randomized trials of fibrinolysis-treated patients with ST-segment elevation myocardial infarction comparing a routine early invasive strategy with a standard approach of percutaneous coronary intervention (PCI) guided by recurrent ischemia or need for rescue. Cox proportional hazards regression was used to examine the interaction between baseline patient risk classified by Thrombolysis in Myocardial Infarction risk score (low/intermediate: ≤ 5 [n = 2,697] vs high: > 5 [n = 277]) and treatment with routine early invasive strategy., Results: Time to PCI after fibrinolysis was longer among patients randomized to standard treatment compared with routine early invasive strategy in the low/intermediate-risk strata (median 11.4 vs 3.5 hours), but was only marginally different between the 2 groups in the high-risk strata (median 4.1 vs 3.5 hours). There was a significant interaction between treatment assignment and risk status for the composite of 30-day death or reinfarction (P = .01). Compared with standard treatment, routine early invasive strategy was associated with lower 30-day death/reinfarction in the low/intermediate-risk stratum (7.5% vs 4.0%, P < .001), but not in the high-risk stratum (14.9% vs 19.6%, P = .45)., Conclusions: Although clearly beneficial among the larger subgroup of patients at low/intermediate risk, the benefit of a routine early invasive strategy was not evident in the smaller subgroup of higher-risk patients in the context of an increased requirement for urgent PCI in the comparative standard treatment arm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers (13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST-segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown., Methods: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days., Results: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used., Conclusions: Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.).

Background: Wide variation exists in the detection rate of obstructive coronary artery disease (CAD) with elective coronary angiography for suspected stable ischemic heart disease. We sought to understand the incremental impact of nonclinical factors on this variation., Methods and Results: We included all patients who underwent coronary angiography for possible suspected stable ischemic heart disease, from October 1, 2008, to September 30, 2011, in Ontario, Canada. Nonclinical factors of interest included physician self-referral for angiography, the physician type (invasive or interventional), and hospital type. Hospitals were categorized into diagnostic angiogram only centers, stand-alone percutaneous coronary intervention centers, or full service centers with coronary artery bypass surgery available. Multivariable hierarchical logistic models were developed to identify system and physician-level predictors of obstructive CAD, after adjustment for patient factors. Our cohort consisted of 60 986 patients, of whom 31 726 had obstructive CAD (52.0%), with significant range across hospitals from 37.3% to 69.2%. Fewer self-referral patients (49.8%) had obstructive CAD compared with nonself-referral patients (53.5%), with an odds ratio of 0.89 (95% confidence interval, 0.86-0.93; P<0.001). Angiograms performed by invasive physicians had a lower likelihood of obstructive CAD compared with those by interventional physicians (48.2% versus 56.9%; odds ratio, 0.85; 95% confidence interval, 0.81-0.90; P<0.001). Fewer angiograms at diagnostic only centers showed obstructive CAD (42.0%) compared with full service centers (55.1%; odds ratio, 0.62; 95% confidence interval, 0.39-0.98; P=0.04). Nonclinical factors accounted for 23.8% of the variation between hospitals., Conclusions: Physician and system factors are important predictors of obstructive CAD with coronary angiography., (© 2014 American Heart Association, Inc.)

Background: Clinical guidelines emphasize medical therapy as the initial approach to the management of patients with stable coronary artery disease (CAD). However, the extent to which medical therapy is applied before and after percutaneous coronary intervention (PCI) in contemporary clinical practice is uncertain. We evaluated medication use for patients with stable CAD undergoing PCI, and assessed whether the COURAGE study altered medication use in the Canadian healthcare system., Methods and Results: A population-based cohort of 23 680 older patients >65 years old) with stable CAD undergoing PCI in Ontario between 2003 and 2010 was assembled. Optimal medical therapy (OMT) was defined as prescription for a β-blocker, statin, and either angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in the 90 days before PCI, and the same medications plus thienopyridine 90 days following PCI. Prior to PCI, 8023 (33.9%) patients were receiving OMT, 11 891 (50.2%) were on suboptimal therapy, and 3766 (15.9%) were not prescribed any medications of interest. There was significant improvement in medical therapy following PCI (OMT: 11 149 [47.1%], suboptimal therapy: 11 591 [48.9%], and none: 940 [4.0%], P<0.001). Utilization rate of OMT reduced significantly after the publication of COURAGE (34.9% before versus 32.8% after, P<0.001). Similarly, the rate of OMT following PCI was lower in the period after publication of COURAGE (47.3% before versus 46.9% after, P<0.001)., Conclusions: OMT was prescribed in about 1 in 3 patients prior to PCI and less than half after PCI. In contrast to the anticipated impact of COURAGE, we found lower rates of medication use in PCI patients after its publication., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: We evaluated the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to glycoprotein (GP) IIb/IIIa inhibitor use., Methods: The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomised 1059 ST elevation myocardial infarction patients to an early invasive strategy or standard therapy post-fibrinolysis. The primary end point was the composite of death, reinfarction, recurrent ischaemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this pre-specified analysis, we examined efficacy and safety outcomes of an early invasive strategy after stratification by GPIIb/IIIa inhibitor use, which was permitted during percutaneous coronary intervention (PCI) at the discretion of the treating physician., Results: A total of 695 patients (65.6%) received GPIIb/IIIa inhibitors. There was significant heterogeneity (p<0.001) in the efficacy of an early invasive strategy compared to standard therapy, between the strata with GPIIb/IIIa inhibitor use (primary end point 9.6% vs 22.3% respectively, p<0.001) and without GPIIb/IIIa inhibitor use (primary end point 14.8% vs 10.4% respectively, p=0.21). Patients who received GPIIb/IIIa inhibitors had lower Global Registry of Acute Coronary Events (GRACE) risk scores compared to those without GPIIb/IIIa inhibitor use (median 121 vs 130, p<0.001). After adjusting for the interaction between GRACE risk score and treatment assignment, the heterogeneity in the efficacy of an early invasive strategy with respect to GPIIb/IIIa inhibitor use was no longer significant (p interaction=0.08)., Conclusions: The apparent difference in the efficacy of an early invasive strategy between GPIIb/IIIa inhibitor strata likely reflects an association between GPIIb/IIIa inhibitor use and baseline risk. GPIIb/IIIa inhibitor use during PCI at the discretion of the treating physician does not appear to modulate the efficacy of an early invasive strategy post-fibrinolysis., Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/show/NCT00164190, NCT00164190.

Objectives: The study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach., Background: RIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021), which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non-coronary artery bypass graft major bleeding., Methods: In pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables., Results: In high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate- (HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p = 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p = 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p = 0.98)., Conclusions: Procedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A major limitation of primary percutaneous coronary intervention (PPCI) for the treatment of ST-elevation myocardial infarction (STEMI) is impaired microvascular perfusion due to embolization and obstruction of microcirculation with thrombus. Manual thrombectomy has the potential to reduce distal embolization and improve microvascular perfusion. Clinical trials have shown mixed results regarding thrombectomy., Objective: The objective of this study is to evaluate the efficacy of routine upfront manual aspiration thrombectomy during PPCI compared with percutaneous coronary intervention alone in patients with STEMI., Design: This is a multicenter, prospective, open, international, randomized trial with blinded assessment of outcomes. Patients with STEMI undergoing PPCI are randomized to upfront routine manual aspiration thrombectomy with the Export catheter (Medtronic CardioVascular, Santa Rosa, CA) or to percutaneous coronary intervention alone. The primary outcome is the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening New York Heart Association class IV heart failure up to 180 days. The trial uses an event-driven design and will recruit 10,700 patients., Summary: The TOTAL trial will determine the effect of routine manual aspiration thrombectomy during PPCI on clinically important outcomes., (Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.)

Background: Disturbed sleep is associated with atherosclerosis in native coronary arteries and may be associated with adverse cardiac events after percutaneous coronary intervention (PCI). We sought to determine the association between symptoms of disturbed sleep and adverse cardiovascular events after PCI., Methods: Outpatients who were stable after successful PCI were assessed for symptoms of disturbed sleep with 10 true/false questions. Follow-up was performed at least 4 years after PCI. The primary outcome was a composite of death, myocardial infarction (MI), and repeated revascularization., Results: Three hundred eighty-eight patients (mean age, 66 ± 11 years) reported on average 3.1 ± 2.1 sleep disturbance symptoms. Follow-up was performed on average 4.4 years after the incident PCI. The primary outcome occurred in 25% of patients. An association was seen between the number of sleep disturbance symptoms and the occurrence of the primary end point. Patients with zero symptoms had a 4-year event rate of 12% compared with a 67% event rate for those with 9 symptoms. On multivariable analysis, sleep symptoms, diabetes mellitus, and the number of diseased coronary vessels were independently associated with the primary end point. Each additional sleep symptom was associated with a hazard ratio (HR) of 1.2 (P = 0.001). The results were driven primarily by the association between symptoms of disturbed sleep and the need for repeated revascularization (repeated PCI HR, 1.9; P = 0.003; coronary artery bypass grafting (CABG) HR, 1.5; P = 0.001)., Conclusions: Symptoms of disturbed sleep were associated with increased risk of long-term adverse cardiovascular outcomes after successful PCI., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Importance: Prior studies have shown that physicians in New York State (New York) perform twice as many cardiac catheterizations per capita as those in Ontario for stable patients. However, the role of patient selection in these findings and their implications for detection of obstructive coronary artery disease (CAD) are largely unknown., Objective: To evaluate the extent of obstructive CAD and to compare the probability of detecting obstructive CAD for patients undergoing cardiac catheterization., Design, Setting, and Patients: An observational study was conducted involving patients without a history of cardiac disease who underwent elective cardiac catheterization between October 1, 2008, and September 30, 2011. Obstructive CAD was defined as diameter stenosis of 50% or more in the left main coronary artery or stenosis of 70% or more in a major epicardial vessel., Main Outcomes and Measures: Observed rates and predicted probabilities of obstructive CAD. Predicted probabilities were estimated using logistic regression models., Results: A total of 18,114 patients from New York and 54,933 from Ontario were included. The observed rate of obstructive CAD was significantly lower in New York at 30.4% (95% CI, 29.7%-31.0%) than in Ontario at 44.8% (95% CI, 44.4%-45.3%; P < .001). The percentage of patients with left main or 3-vessel CAD was also significantly lower in New York than in Ontario (7.0% [95% CI, 6.6%-7.3%] vs 13.0% [95% CI, 12.8%-13.3%]; P < .001). In New York, a substantially higher percentage of patients with low predicted probability of obstructive CAD underwent cardiac catheterization; for example, only 19.3% (95% CI, 18.7%-19.9%) of patients undergoing cardiac catheterization in New York had a greater than 50% predicted probability of having obstructive CAD than those in Ontario at 41% (95% CI, 40.6%-41.4%; P < .001). At 30 days, crude mortality for patients undergoing cardiac catheterization was slightly higher in New York at 0.65% (90 of 13,824; 95% CI, 0.51%-0.78%) than in Ontario at 0.38% (153 of 40,794; 95% CI, 0.32%-0.43%; P < .001)., Conclusions and Relevance: In Ontario compared with New York State, patients undergoing elective cardiac catheterization were significantly more likely to have obstructive CAD. This appears to be related to a higher percentage of patients in New York with low predicted probability of CAD undergoing cardiac catheterization.

Background: In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI)., Methods: We report prespecified secondary clinical outcomes and cost implications of r-PCI compared with s-PCI from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was calculated based on a microcosting approach. Bootstrap method (5,000 samples) was used to calculate standard errors and 95% CI., Results: At 1 year, rates of death or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%, P = .64) and subsequent revascularization after index hospitalization (6.9% vs 8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to $2,211). Since a greater proportion of patients were transported by air (vs land) in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional post hoc cost scenario analyses. In a scenario where patients are transported by land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the difference in cost per patient between r-PCI and s-PCI was estimated to be CAD $108 (95% CI, -$1,114 to $1,344)., Conclusions: At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Long-term outcome after bifurcation stenting with drug-eluting stents (DES) for obstructive coronary artery disease is poorly understood. In this study, we report 6-9-month angiographic follow-up and long-term clinical outcomes after implantation of drug-eluting stents by crush and kissing stent technique for coronary bifurcation lesions., Methods: Consecutive patients undergoing bifurcation stenting with DES by crush or kissing stent technique were enrolled in a prospective registry. Angiographic follow-up was obtained at 6-9 months and clinical follow-up completed for a median of 38 months., Results: A total of 86 patients participated in the study. Bifurcation stenting by crush technique was performed in 73 (85%) and by kissing stent in 13 (15%) patients. Stenting of left main bifurcation was applied in 24 (28%) patients. Angiographic follow-up was completed in 75 (87%) patients and showed restenosis in the main for 8 (11%) and side branch for 20 (27%) patients. Clinical follow-up was available for a median duration of 38 months. During follow-up, 2 (2%) patients died, 4 (5%) experienced myocardial infarction (MI), and 11 (13%) underwent target vessel revascularization (TVR) with an overall major adverse cardiac event (MACE) rate of 16%. In left main cohort, angiographic restenosis occurred in 9 (37%) patients, and 3 (12%) patients required TVR. There were no deaths or stent thrombosis. A comparison of crush and kissing stent technique showed significantly higher angiographic restenosis with crush (26% vs 13% in kissing stent patients, P = 0.046) and 95% of restenosis in crush group involved ostium of the side branch. There was no difference in clinical outcomes between the crush and kissing stent groups. Final kissing balloon dilatation (FKB) was successful in 65 (89%) patients in the crush group and associated with a significant reduction in MACE (8% in FKB successful vs 37% in FKB unsuccessful, P = 0.04) during follow-up., Conclusion: Bifurcation stenting with crush or kissing stent technique is safe and associated with a low rate of TLR and MACE on long-term follow-up. Crush stenting is associated with a significantly higher rate of side branch restenosis compared to kissing stent technique. FKB is associated with significant reduction in MACE during follow-up., (© 2013, Wiley Periodicals, Inc.)

Objectives: The authors sought to compare the radiation dose between radial and femoral access., Background: Small trials have shown an increase in the radiation dose with radial compared with femoral access, but many were performed during the operators' learning curve of radial access., Methods: Patients were randomized to radial or femoral access, as a part of the RIVAL (RadIal Vs. femorAL) trial (N = 7,021). Fluoroscopy time was prospectively collected in 5740 patients and radiation dose quantified as air kerma in 1,445 patients and dose-area product (DAP) in 2,255 patients., Results: Median fluoroscopy time was higher with radial versus femoral access (9.3 vs. 8.0 min, p < 0.001). Median air kerma was nominally higher with radial versus femoral access (1,046 vs. 930 mGy, respectively, p = 0.051). Median DAP was not different between radial and femoral access (52.8 Gy-cm(2) vs. 51.2 Gy·cm(2), p = 0.83). When results are stratified according to procedural volume, air kerma was increased only in the lowest tertile of radial volume centers (low 1,425 vs. 1,045 mGy, p = 0.002; middle 987 vs. 958 mGy, p = 0.597; high 652 vs. 621 mGy, p = 0.403, interaction p = 0.026). Multivariable regression showed procedural volume was the greatest independent predictor of lower air kerma dose (ratio of geometric means 0.55; 95% confidence interval 0.49 to 0.61 for highest-volume radial centers)., Conclusions: Radiation dose as measured by air kerma was nominally higher with radial versus femoral access, but differences were present only in lower-volume centers and operators. High-volume centers have the lowest radiation dose irrespective of which access site approach that they use. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention (PCI) Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered., Methods and Results: We analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44)., Conclusion: This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.