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Introduction: Stable angina pectoris (SAP) is a widely prevalent disease affecting 30 000 to 40 000 per million people in Europe and the US. SAP is associated with reductions in quality of life and ability to work, and increased use of healthcare resources. Ivabradine is a drug with a unique therapeutic target, the if current of the sinus node, developed for the treatment of cardiovascular diseases including SAP. It has an exclusive heart rate reducing effect, without any negative effect on left ventricular function or coronary vasodilatation. Aims: The aim of this paper is to review the evidence concerning the use of ivabradine in the treatment of SAP. Evidence review: Ivabradine is an effective antianginal and antiischemic drug, not inferior to the beta blocker atenolol and the calcium channel antagonist (CCA) amlodipine. It decreases the frequency of angina attacks and increases the time to anginal symptoms during exercise. Because of its exclusive chronotropic effect, ivabradine is not associated with the typical adverse reactions associated with beta blockers or other antianginal drugs. Clinical value: Clinical evidence shows that ivabradine is a very good antiischemic and antianginal agent, being as effective as beta blockade and CCA therapy in controlling myocardial ischemia and symptoms of stable angina. Ongoing studies will determine the potential of ivabradine to improve morbidity and mortality in coronary artery disease and heart failure. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD)., Design: A secondary analysis of the randomised controlled trial ADAPTABLE was performed., Setting: The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA., Participants: Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%)., Interventions: Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months., Primary and Secondary Outcomes Measures: The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion., Results: Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints., Conclusion: Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race., Trial Registration Number: NCT02697916., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The incidence of coronary artery aneurysm is between 1.4% and 4.9% based on autopsy or angiographic series. Mycotic coronary arteries aneurysms are very rare and represent less than 3% of all coronary aneurysms. We report the case of a patient who presented with multiple coronary mycotic aneurysms., Competing Interests: Vincent Chauvette is a Vanier Scholarship recipient. Guillaume Marquis-Gravel is a Junior Clinical Research Scholar of the Fonds de Recherche du Québec–Santé. André Denault is supported by the Richard I. Kaufman Endowment Fund in Anesthesia and Critical Care. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

The coronary angiogram is the gold standard for evaluating the severity of coronary artery disease stenoses. Presently, the assessment is conducted visually by cardiologists, a method that lacks standardization. This study introduces DeepCoro, a ground-breaking AI-driven pipeline that integrates advanced vessel tracking and a video-based Swin3D model that was trained and validated on a dataset comprised of 182,418 coronary angiography videos spanning 5 years. DeepCoro achieved a notable precision of 71.89% in identifying coronary artery segments and demonstrated a mean absolute error of 20.15% (95% CI: 19.88-20.40) and a classification AUROC of 0.8294 (95% CI: 0.8215-0.8373) in stenosis percentage prediction compared to traditional cardiologist assessments. When compared to two expert interventional cardiologists, DeepCoro achieved lower variability than the clinical reports (19.09%; 95% CI: 18.55-19.58 vs 21.00%; 95% CI: 20.20-21.76, respectively). In addition, DeepCoro can be fine-tuned to a different modality type. When fine-tuned on quantitative coronary angiography assessments, DeepCoro attained an even lower mean absolute error of 7.75% (95% CI: 7.37-8.07), underscoring the reduced variability inherent to this method. This study establishes DeepCoro as an innovative video-based, adaptable tool in coronary artery disease analysis, significantly enhancing the precision and reliability of stenosis assessment., (© 2024. The Author(s).)

Acute coronary syndromes (ACS), encompassing conditions like ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndromes (NSTE-ACS), represent a significant challenge in cardiovascular care due to their complex pathophysiology and substantial impact on morbidity and mortality. The 2023 European Society of Cardiology (ESC) guidelines for ACS management introduce several updates in key areas such as invasive treatment timing in NSTE-ACS, pre-treatment strategies, approaches to multivessel disease, and the use of imaging modalities including computed tomography (CT) coronary angiography, magnetic resonance imaging (MRI), and intracoronary imaging techniques, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS). They also address a modulation of antiplatelet therapy, taking into consideration different patient risk profiles, and introduce new recommendations for low-dose colchicine. These guidelines provide important evidence-based updates in practice, reflecting an evolution in the understanding and management of ACS, yet some potentially missed opportunities for more personalized care and technology adoption are discussed.

Background: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease., Methods and Results: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant ( P =0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points ( P >0.05 for all)., Conclusions: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Background: Ongoing debate remains regarding optimal antithrombotic therapy in patients with atrial fibrillation (AF) and coronary artery disease., Methods: We performed a systematic review and meta-analysis to synthesize randomized controlled trials (RCTs) comparing the following: (i) dual-pathway therapy (DPT; oral anticoagulant [OAC] plus antiplatelet) vs triple therapy (OAC and dual-antiplatelet therapy) after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS), and (iii) OAC monotherapy vs DPT at least 1 year after PCI or ACS. Following a 2-stage process, we identified systematic reviews published between 2019 and 2022 on these 2 clinical questions, and we updated the most comprehensive search for additional RCTs published up to October 2022. Outcomes of interest were major adverse cardiovascular events (MACE), death, stent thrombosis, and major bleeding. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model., Results: Based on 6 RCTs (n = 10,435), DPT reduced major bleeding (RR 0.62, 95% CI 0.52-0.73) and increased stent thrombosis (RR 1.55, 95% CI 1.02-2.36), vs triple therapy after PCI or medically-managed ACS, with no significant differences in MACE and death. In 2 RCTs (n = 2905), OAC monotherapy reduced major bleeding (RR 0.66, 95% CI 0.49-0.91) vs DPT in AF patients with remote PCI or ACS, with no significant differences in MACE or death., Conclusions: In patients with AF and coronary artery disease, using less-aggressive antithrombotic treatment (DPT after PCI or ACS, and OAC alone after remote PCI or ACS) reduced major bleeding, with an increase in stent thrombosis with recent PCI. These results support a minimalist yet personalized antithrombotic strategy for these patients., (© 2024 The Authors.)

Purpose: Even though transjugular intrahepatic portosystemic shunt (TIPS) using Fluency Stent-grafts provides good shunt patency rates, shunt dysfunction is a great concern after TIPS creation, occurring in up to 20% of cases within one year. The objective of this study was to describe shunt dysfunction patterns after TIPS creation using a combination of generic stent-grafts/bare-stents., Materials and Methods: Single-center retrospective study of all TIPS revisions between January 2005 and December 2020. TIPS revision angiograms were analyzed for stents' positions, stenoses' diameters, and stenoses' locations., Results: Out of 99 TIPS, a total of 33 TIPS revisions were included. The median time to TIPS revision was 10.4 months. Angiograms showed four patterns of TIPS dysfunction-associated features (DAF), defined as follows: Type 1 was defined as stenosis located after the stent end in the hepatic vein (HV), type 2 as intra-stent stenosis located in the hepatic vein, type 3 as intra-stent stenosis or a kink in the parenchymal tract or the portal vein end of the TIPS, and type 4 as a complete TIPS occlusion. Types 1, 2, 3, and 4 were seen in 23 (69.7%), 5 (15.2%), 2 (6.1%), and 3 (9.1%) TIPS respectively. TIPS revision was successful in 30 (90.1%) patients with median pre- and post-TIPS revision PSG of 18.5 mmHg and 8 mmHg respectively (p < .001)., Conclusion: Our results illustrate the four angiographic patterns of TIPS DAF after TIPS creation using a combination of generic stent-grafts/bare-stents and emphasize the need for appropriate stent length extending to the HV/inferior vena cava junction., (© 2024. The Author(s).)

Background: Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent purinergic receptor type Y, subtype 12 (P2Y 12 ) inhibitors remains a challenge in the management of acute coronary syndrome (ACS)., Methods: We conducted a systematic review and meta-analysis following a 2-stage process consisting of searching for systematic reviews published between 2019 and November 2022. We included randomized controlled trials (RCTs) of ACS patients treated with percutaneous coronary intervention comparing (i) ticagrelor- vs prasugrel-based DAPT and (ii) P2Y 12 inhibitor de-escalation strategies. Outcomes of interest were major adverse cardiovascular events (MACE), all-cause death, stent thrombosis, and major bleeding. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model., Results: Eight RCTs (n = 5571) compared ticagrelor to prasugrel. Ticagrelor was associated with an increased risk of MACE compared to prasugrel (RR 1.23, 95% CI 1.01-1.49, moderate certainty), without significant differences in death, stent thrombosis, or major bleeding. In 2 RCTs (n = 3343) comparing clopidogrel-based DAPT de-escalation after 1 month to potent P2Y 12 inhibitor-based DAPT continuation, clopidogrel de-escalation did not significantly alter the incidence of MACE, death, or stent thrombosis, but reduced that of major bleeding (RR 0.51, 95% CI 0.28-0.92, high certainty). The effect of prasugrel dose de-escalation was inconclusive for all outcomes based on one trial., Conclusions: Ticagrelor was associated with an increase in MACE compared with prasugrel, based on low-certainty evidence, whereas de-escalation to clopidogrel after 1 month of potent P2Y 12 inhibitor was associated with a decrease in incidence of major bleeding without increasing thrombotic outcomes in ACS patients post-percutaneous coronary intervention., (© 2023 The Authors.)

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown., Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model., Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge ( P  = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately., Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs., (© 2023 The Authors.)

Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Background: In Canada, gonorrhea is the second most prevalent bacterial sexually transmitted infection. The Gonococcal Antimicrobial Surveillance Programme (GASP - Canada), a passive surveillance system monitoring antimicrobial resistance in Neisseria gonorrhoeae in Canada since 1985, is the source for this summary of demographics, antimicrobial resistance and N. gonorrhoeae multi-antigen sequence typing (NG-MAST) of gonococcal isolates collected in Canada in 2021., Methods: Provincial and territorial public health laboratories submitted N. gonorrhoeae cultures and data to the National Microbiology Laboratory in Winnipeg as part of the surveillance system. The antimicrobial resistance and molecular type of each isolate received were determined., Results: In total, 3,439 N. gonorrhoeae cultures were received from laboratories across Canada in 2021, a 9.9% increase since 2020 (n=3,130). Decreased susceptibility to cefixime increased significantly ( p <0.001) in 2021 (1.5%) compared to 2017 (0.6%). No significant change in decreased susceptibility to ceftriaxone was detected between 2017 and 2021 (0.6%) ( p >0.001); however, one ceftriaxone-resistant isolate was identified. Azithromycin resistance decreased significantly ( p <0.001) in 2021 (7.6%) compared to 2017 (11.7%); however, there was a significant increase ( p <0.001) in the proportion of cultures with an azithromycin minimum inhibitory concentration of at least 1 mg/L (2017=22.2% to 2021=28.1%). In 2021, NG-MAST-19875 (15.3%) was the most prevalent sequence type in Canada; 20.3% of isolates with this sequence type were resistant to azithromycin., Conclusion: The spread of antimicrobial-resistant gonorrhea is a significant public health concern. The continued regional and national surveillance of antimicrobial resistance in N. gonorrhoeae is essential in ensuring effective treatment therapies are recommended., Competing Interests: Competing interests None.

Introduction: Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) reduces major adverse cardiovascular events (MACE) and stent thrombosis. However, DAPT duration is a concern in high bleeding risk (HBR) patients. We evaluated the effect of short DAPT (1-3 months) compared to standard DAPT (6-12 months) on bleeding and ischemic events in HBR PCI., Methods: We searched MEDLINE, Embase and CENTRAL up to August 18, 2022. Randomized controlled trials (RCTs) comparing short DAPT (1-3 months) versus standard DAPT in HBR PCI were included. We assessed risk of bias (RoB) using the Cochrane RoB2 tool, and certainty of evidence using GRADE criteria. Outcomes included MACE, all-cause death, stent thrombosis, major bleeding, and the composite of major or clinically-relevant non-major bleeding. We estimated risk ratios (RR) and 95% confidence intervals (CI) using a random-effects model., Results: From 503 articles, we included five RCTs (n = 7,242) at overall low risk of bias with median follow-up of 12-months. Compared to standard DAPT, short DAPT did not increase MACE (RR 1.02, 95% CI 0.84-1.23), all-cause death (RR 0.92, 95% CI 0.71-1.20) or stent thrombosis (RR 1.47, 95% CI 0.73-2.93). Short DAPT reduced major bleeding (RR 0.34, 95% CI 0.13-0.90) and the composite of major or clinically-relevant non-major bleeding (RR 0.60, 95% CI 0.44-0.81), translating to 21 and 34 fewer events, respectively, per 1000 patients., Conclusions: In HBR PCI, DAPT for 1-3 months compared to 6-12 months reduced clinically-relevant bleeding events without jeopardizing ischemic risk. Short DAPT should be considered in HBR patients receiving PCI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bainey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Since the publication of the 2010 Canadian antiplatelet guidelines, several large randomized controlled trials (RCTs) have evaluated the role of aspirin (ASA) use in primary prevention. We evaluated the effect of ASA use, compared with no ASA, on ischemic and bleeding events in patients without known atherosclerotic cardiovascular diseases., Methods: We updated a published systematic review and meta-analysis by searching MEDLINE, Embase, and CENTRAL for the period up to March 2023. We included RCTs that enrolled patients for primary prevention of atherosclerotic cardiovascular diseases, and compared use of ASA to no ASA. We assessed risk of bias (RoB) using the Cochrane RoB tool, and certainty of evidence using the grading recommendations, assessment, development, and evaluation (GRADE) criteria. The primary efficacy outcome was major adverse cardiovascular events (MACE) (death, myocardial infarction, or stroke). The primary safety outcomes were intracranial hemorrhage and extracranial major bleeding events. We used a random-effects model to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs)., Results: We included 14 RCTs (n = 167,587) at overall low RoB, with a median follow-up of 5 years. Compared to no ASA, ASA use reduced the incidence of MACE (RR 0.90, 95% CI 0.86-0.94), with a higher risk of intracranial hemorrhage (RR 1.33, 95% CI 1.13-1.56) and extracranial major bleeding (RR 1.67, 95% CI 1.36-2.06). In prespecified subgroups of age, sex, and diabetes, effect estimates were consistent., Conclusions: ASA use in primary prevention is associated with a consistent reduction in MACE, but at the expense of major bleeding events. Patient values and preferences should be taken into account when considering ASA use for primary prevention., (© 2023 The Authors.)

Background: Coronary artery bypass grafting (CABG) is the recommended mode of revascularization in patients with ischemic left ventricular dysfunction (iLVSD) and multivessel disease. However, contemporary percutaneous coronary intervention (PCI) outcomes have improved with the integration of novel technologies and refinement of revascularization strategies, and PCI is often used in clinical practice in this population. There is a lack of evidence from randomized trials comparing contemporary state-of-the-art PCI versus CABG for the treatment of iLVSD and multivessel disease. This was the impetus for the STICH3C trial (Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy), described here., Methods: The STICH3C trial is a prospective, unblinded, international, multicenter trial with an expected sample size of 754 participants from ≈45 centers. Patients with multivessel/left main coronary artery disease and iLVSD with left ventricular ejection fraction ≤40% considered by the local Heart Team appropriate for and amenable to revascularization by both modes of revascularization will be randomized in a 1:1 ratio to state-of-the-art PCI or CABG., Results: The primary end point is the composite of death from any cause, stroke, spontaneous myocardial infarction, urgent repeat revascularization, or heart failure readmission, summarized as a time-to-event outcome. The key hierarchical end point is time to death and frequency of hospitalizations for heart failure. The key safety outcome is a composite of major adverse events. Disease-specific quality-of-life and health economics measures will be compared between groups. Participants will be followed for a median of 5 years, with a minimum follow-up of 4 years., Conclusions: STICH3C will directly inform patients, clinicians, and international practice guidelines about the efficacy and safety of CABG versus PCI in patients with iLVSD. The results will provide novel and broad evidence, including clinical events, health status, and economic assessments, to guide care for patients with iLVSD and severe coronary artery disease., Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT05427370., Competing Interests: Disclosures Dr Vervoort is supported by the Canadian Institutes of Health Research Vanier Canada Graduate Scholarship. The other authors report no conflicts.

Purpose: To describe the leadership performance of team leaders and CPR Coaches, and to determine if there is a correlation between leadership scores and CPR performance during management of simulated pediatric cardiac arrest events., Methods: This is a secondary analysis of data from a prior randomized controlled trial. We observed the performance of both team leaders and CPR coaches during the management of an 18-minute simulated cardiac arrest scenario which was run for 20 resuscitation teams comprised of CPR-certified professionals from four pediatric tertiary care centers. CPR Coaches were responsible for providing real-time verbal feedback of CPR performance to compressors. Two raters were trained to use the Behavioral Assessment Tool (BAT) to assess leadership performance of the team leader and CPR Coach. BAT scores of team leaders and CPR coaches were compared and linked with objective CPR performance., Results: There was no significant difference between the BAT scores of team leaders and CPR coaches (median score 27/40 vs 28.8/40, p  = 0.16). Higher BAT scores of team leaders were significantly associated with higher percentage of excellent CPR ( r  = 0.52, p  = 0.02), while higher BAT scores of CPR coaches were significantly associated with higher chest compression fraction ( r  = 0.48, p  = 0.03)., Conclusions: Both team leaders and CPR coaches have similarly high leadership performance during the management of simulated cardiac arrest. Leadership behaviors were associated with quality of CPR performance. Clinical Trial Registration : Registration ID: NCT02539238; https://www.clinicaltrials.gov., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Yiqun Lin is a volunteer for the American Heart Association (Resuscitation Education Summit and Education Writing Group) and the International Liaison Committee for Resuscitation. Dr. Adam Cheng is a volunteer for the American Heart Association (Resuscitation Education Summit and Education Writing Group) and the International Liaison Committee for Resuscitation (Domain Lead, Education). The other authors have no other relevant disclosures.’., (© 2023 The Author(s).)

Background The effectiveness of vascular closure devices (VCDs) to reduce bleeding after transfemoral percutaneous coronary intervention remains unsettled. Methods and Results Participants in the REGULATE-PCI (Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention) trial who underwent transfemoral percutaneous coronary intervention with VCD implantation were compared with those who underwent manual compression. The primary effectiveness end point was type 2, 3, or 5 Bleeding Academic Research Consortium access site bleeding at day 3. Univariate and multivariate analyses were adjusted by the inverse probability weighting method using propensity score. Time to hemostasis and time to ambulation were compared between groups. Of the 1580 patients who underwent transfemoral percutaneous coronary intervention, 1004 (63.5%) underwent VCD implantation and 576 (36.5%) had manual compression. The primary effectiveness end point occurred in 64 (6.4%) participants in the VCD group and in 38 (6.6%) participants in the manual compression group (inverse probability weighting-adjusted odds ratio, 1.02 [95% CI, 0.77-1.36]; P =0.89). There were statistically significant 2-way interactions between VCD use and female sex, chronic kidney disease, and use of high-potency P2Y12 inhibition (ticagrelor or prasugrel) ( P <0.05 for all) with less bleeding with VCD use in these high-risk subgroups. Median time to hemostasis and time to ambulation were shorter in the VCD versus the manual compression group ( P <0.01 for both). Conclusions Following transfemoral percutaneous coronary intervention, VCD use is associated with a shorter time to hemostasis and time to ambulation but not less bleeding. Further study of patients with high-bleeding risk is required, including women, patients with chronic kidney disease, and those using high-potency P2Y12 inhibitors. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01848106; Unique identifier: NCT01848106.

Objectives: The objective is to assess the comparative effectiveness and safety of dual-antiplatelet therapy (DAPT) vs triple therapy (TT) with DAPT + oral anticoagulant (OAC) in patients with anterior ST-segment elevation myocardial infarction (STEMI) and with new-onset anterior/apical wall-motion abnormalities (WMAs) treated with primary percutaneous coronary intervention (PCI)., Background: Patients with STEMI and new-onset anterior/apical WMA may benefit from the addition of OAC to prevent left ventricular thrombus and cardioembolic events., Methods: A multicenter, retrospective cohort study was conducted. Patients with a concomitant indication for OAC were excluded. Patients discharged on TT were compared with patients discharged on DAPT using adjusted Cox proportional hazards analysis and inverse probability of treatment weighting. The primary endpoint was the net adverse clinical event (NACE) rate at 6 months (composite of all-cause mortality, non-fatal MI, stroke, or transient ischemic attack, systemic thromboembolism or type 3 or 5 Bleeding Academic Research Consortium [BARC] bleeding)., Results: A total of 1666 patients were included, among which 627 were treated with TT and 1039 were treated with DAPT. A NACE occurred in 55 patients (6.03 per 100 patient-years) in the TT group and in 74 patients (7.18 per 100 patient-years) in the DAPT group (adjusted hazard ratio, 0.86; 95% confidence interval, 0.55-1.32). Adjusted risk of the individual components of the primary endpoint, ischemic events, and bleeding events were similar between both groups (P>.05 for all)., Conclusions: The addition of OAC to DAPT in anterior STEMI patients with new-onset WMA treated with PCI was not associated with a significant reduction in NACE.

Background: The Gonococcal Antimicrobial Surveillance Programme is a passive surveillance system that has monitored antimicrobial resistance in Neisseria gonorrhoeae in Canada since the 1980s. This article summarizes the demographics, antimicrobial resistances and NG-MAST ( N. gonorrhoeae multiantigen sequence typing) for cultures collected in 2020., Methods: The National Microbiology Laboratory (NML) in Winnipeg received resistant N. gonorrhoeae cultures from provincial and territorial public health laboratories. Agar dilution was used to determine the minimum inhibitory concentrations to ten antimicrobials for all cultures received at NML, according to Clinical and Laboratory Standards Institute guidelines. The NG-MAST typing was also determined for each culture., Results: A total of 3,130 N. gonorrhoeae cases were cultured across Canada in 2020; a 36% decrease from 2019 (n=4,859). The level of decreased susceptibility to cefixime increased significantly between 2016 and 2020 to 2.8% ( p =0.0054). Decreased susceptibility to ceftriaxone declined significantly between 2016 (1.8%) and 2020 to 0.9% ( p =0.001), and there was no significant change with azithromycin between 2016 (7.2%) and 2020 (6.1%). The proportion of cultures with an azithromycin minimum inhibitory concentrations of ≥1 mg/L increased significantly from 11.6% in 2016 to 15.3% in 2020 ( p =0.0017). The most common NG-MAST type in Canada for 2020 was sequence type (ST)-11461, while ST-12302 was most commonly associated with azithromycin resistance and ST-16639 with cephalosporin decreased susceptibility., Conclusion: Antimicrobial resistance in N. gonorrhoeae remains an important public health concern and continued surveillance is imperative to monitor trends to ensure the recommended therapies will be the most effective., Competing Interests: Competing interests None.

Background: Peripartum cardiomyopathy (PPCM) is associated with severe morbidity and mortality, and the significance of right ventricular (RV) involvement is unclear. We sought to determine whether RV systolic dysfunction or dilatation is associated with adverse clinical outcomes in women with PPCM., Methods: We conducted a multicentre retrospective cohort study examining the association between echocardiographic RV systolic dysfunction or dilatation at the time of PPCM diagnosis and clinical outcomes. Clinical endpoints of interest were the need for mechanical support, recovery of left ventricular ejection fraction at follow-up, and a combined endpoint of hospitalization for heart failure, cardiac transplant, or death., Results: A total of 67 women, median age 30 years (interquartile range: 7), were diagnosed with PPCM between 1994 and 2015 in 17 participating centres. Twin pregnancies occurred in 11%; 62% of women were multiparous; and 24% had preeclampsia. RV systolic function was impaired in 18 (27%) and dilated in 8 (12%). Seven women required ventricular assistance, and 8 experienced the composite outcome during follow-up (25 [interquartile range 61] months). RV dysfunction was associated with the need for mechanical support (odds ratio 10.10 (95% confidence interval: 1.86-54.81), P  = 0.007), but neither RV dysfunction nor dilatation was associated with left ventricular ejection fraction recovery, the need for cardiac transplant, heart failure hospitalization, or death., Conclusions: RV dysfunction is associated with the need for mechanical support in women with PPCM. These findings may improve risk stratification of complications and clinical management., (© 2022 The Authors.)

Background: Mechanical circulatory support (MCS) devices can be used in high-risk percutaneous coronary intervention (PCI). Our objective was to describe trends and outcomes of prophylactic MCS use in elective PCI for patients with stable coronary artery disease in the American College of Cardiology National Cardiovascular Data Registry's CathPCI registry., Methods: Among 2 108 715 consecutive patients with stable coronary artery disease undergoing elective PCI in the CathPCI registry between 2009 and 2018, we examined patterns of prophylactic use of MCS. Propensity score models with inverse probability of treatment weighting compared effectiveness (in-hospital death, cardiogenic shock, or new heart failure) and safety (stroke, tamponade, major bleeding, or vascular complication requiring treatment) between patients treated with intra-aortic balloon pump versus other MCS (Impella or extracorporeal membrane oxygenation)., Results: Overall, 6905 (0.3%) patients underwent elective PCI with prophylactic MCS. MCS use trended up from 0.2% of elective PCIs in 2009 to 0.6% in 2018 ( P <0.0001), driven by other MCS ( P <0.0001), whereas intra-aortic balloon pump use remained low and constant ( P =0.12). In-hospital major adverse cardiac events and cardiovascular complications occurred in 7.1% and 18.8% of elective PCI patients with prophylactic MCS use and 0.5% and 2.3% of patients without prophylactic MCS use. Intra-aortic balloon pump use was associated with a higher risk of major adverse cardiac events (9.6% versus 6.0%, adjusted odds ratio, 1.59 [95% CI, 1.32-1.91]) but lower risk of complications (18.2% versus 19.1%, adjusted odds ratio, 0.88 [95% CI, 0.77-0.99]) than use of other MCS., Conclusions: The use of prophylactic MCS has increased over time for elective PCI in patients with stable coronary artery disease. Intra-aortic balloon pump was associated with higher major adverse cardiac events but lower risk of procedural complications compared with other MCS.

Antiplatelet therapy, mainly consisting of aspirin and P2Y 12 receptor antagonists, is the cornerstone of the pharmacological treatment and prevention of atherothrombotic diseases. Its use, especially in secondary cardiovascular prevention, has significantly improved patient clinical outcomes in the last decades. Primary safety endpoint (i.e., bleeding complications) remain a major drawback of antiplatelet drugs. National and international societies have published and regularly updated guidelines for antiplatelet therapy aiming to provide clinicians with practical recommendations for a better handling of these drugs in various clinical settings. Many recommendations find common ground between international guidelines, but certain strategies vary across the countries, particularly with regard to the choice of molecules, dosage, and treatment duration. In this review, we detail and discuss the main antiplatelet therapy indications in the light of the different published guidelines and the significant number of recently published clinical trials and meta-analyses and highlight the areas that deserve further investigation in order to improve antiplatelet therapy in patients with atherothrombotic diseases., Competing Interests: ML has received speaker fees from Bayer; has participated in industry-funded trials from Idorsia; has served on advisory boards for Servier and JAMP/Orimed Pharma; and has received in-kind and financial support for investigator-initiated grants from Leo Pharma, Roche Diagnostics, Aggredyne and Fujimori Kogyo. GM-G reports consulting and/or speaker fees from Pharmascience, Bayer, KYE, JAMP Pharma, Novartis, Population Health Research Institute, and Canadian Heart Research Center; and research funding from Bayer, FRQS, University de Montreal (department of medicine), and Montreal Heart Institute Foundation. AG has received honoraria and travel fees from Bayer-Healthcare, Boehringer-Ingelheim, Bristol-Myers-Squibb/Pfizer and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jourdi, Marquis-Gravel, Martin, Lordkipanidzé, Godier and Gaussem.)

Antiplatelet agents, with aspirin and P2Y 12 receptor antagonists as major key molecules, are currently the cornerstone of pharmacological treatment of atherothrombotic events including a variety of cardio- and cerebro-vascular as well as peripheral artery diseases. Over the last decades, significant changes have been made to antiplatelet therapeutic and prophylactic strategies. The shift from a population-based approach to patient-centered precision medicine requires greater awareness of individual risks and benefits associated with the different antiplatelet strategies, so that the right patient gets the right therapy at the right time. In this review, we present the currently available antiplatelet agents, outline different management strategies, particularly in case of bleeding or in perioperative setting, and develop the concept of high on-treatment platelet reactivity and the steps toward person-centered precision medicine aiming to optimize patient care., Competing Interests: AG reports honoraria and travel fees from Bayer-Healthcare, Boehringer-Ingelheim, Bristol-Myers-Squibb/Pfizer, LFB, Octapharma, and Sanofi. ML has received speaker fees from Bayer; has participated in industry-funded trials from Idorsia; has served on advisory boards for Servier and JAMP/Orimed Pharma; and has received in-kind and financial support for investigator-initiated grants from Leo Pharma, Roche Diagnostics, Aggredyne, and Fujimori Kogyo. GM-G reports speaker fees and advisory board fees from JAMP Pharma, and research funding from Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jourdi, Godier, Lordkipanidzé, Marquis-Gravel and Gaussem.)

Background Clinical evidence on the safety and effectiveness of using direct oral anticoagulants (DOACs) in patients with atrial fibrillation after transcatheter aortic valve replacement (TAVR) remains limited. The aim of this study was to investigate the trends and outcomes of using DOACs in patients with TAVR and atrial fibrillation. Methods and Results Data from the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry was used to identify patients who underwent successful TAVR with preexisting or incident atrial fibrillation who were discharged on oral anticoagulation between January 2013 and May 2018. Patients with a mechanical valve, valve-in-valve procedure, or prior stroke within a year were excluded. The adjusted primary outcome was 1-year stroke events. The adjusted secondary outcomes included bleeding, intracranial hemorrhage, and death. A total of 21 131 patients were included in the study (13 004 TAVR patients were discharged on a vitamin K antagonist and 8127 were discharged on DOACs.) The use of DOACs increased 5.5-fold from 2013 to 2018. The 1-year incidence of stroke was comparable between DOAC-treated patients and vitamin K antagonist-treated patients (2.51% versus 2.37%; hazard ratio [HR], 1.00; 95% CI, 0.81-1.23) whereas DOAC-treated patients had lower 1-year incidence of any bleeding (11.9% versus 15.0%; HR, 0.81; 95% CI, 0.75-0.89), intracranial hemorrhage (0.33% versus 0.59%; HR, 0.54; 95% CI, 0.33-0.87), and death (15.8% versus 18.2%; HR, 0.92; 95% CI, 0.85-1.00). Conclusions In patients with TAVR and atrial fibrillation, DOAC use, when compared with vitamin K antagonists, was associated with comparable stroke risk and significantly lower risks of bleeding, intracranial hemorrhage, and death at 1 year.

Background: Older adults with atrial fibrillation (AF) are often treated with the shortest possible duration of antiplatelet/anticoagulant therapy after myocardial infarction (MI) or percutaneous coronary intervention (PCI) due to concern for bleeding. However, the risk of recurrent MI or PCI prompting antiplatelet therapy extension is unknown in this population., Methods: Using the National Cardiovascular Data Registry linked to Medicare claims, we described the cumulative incidence of recurrent MI or PCI over a median of 7-year follow-up for patients ≥65 years old with AF discharged alive after acute MI between 2008 and 2017. We used pharmacy fill data to describe the proportion of patients filling prescriptions for both oral anticoagulants and P2Y 12 inhibitors for ≥50% of the indicated duration after MI or PCI., Results: Of 187 622 older patients discharged alive after MI, 50 539 (26.9%) had AF. Over a median of 7-year follow-up in patients with AF, the cumulative incidence was 14.5% for recurrent MI, 12.1% for PCI, 7.9% for stroke, and 9.5% for bleeding hospitalization. Among 7998 patients with AF and recurrent MI or PCI, 1668 (20.9%) had >1 MI or PCI during follow-up. Assuming each MI or PCI should be followed by 6 months of P2Y 12 inhibitor therapy, patients with AF who had a recurrent MI/PCI had a median estimated indication for antiplatelet/anticoagulant treatment of 287 days (194, 358), but filled both P2Y 12 inhibitor and oral anticoagulant for a median of 0 days (0, 21). In this cohort, 12.2% of patients filled prescriptions for both a P2Y 12 inhibitor and oral anticoagulant for ≥50% of the indicated duration., Conclusions: Older adults with AF and MI have high incidences of downstream recurrent MI or PCI requiring extended antiplatelet/anticoagulant therapy durations, yet many appear to be under-treated. These results highlight the need for better thrombosis prevention strategies in this group of patients.

Background: The ADAPTABLE trial (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) is the first randomized trial conducted within the National Patient-Centered Clinical Research Network to use the electronic health record data formatted into a common data model as the primary source of end point ascertainment, without confirmation by standard adjudication. The objective of this prespecified study is to assess the validity of nonfatal end points captured from the National Patient-Centered Clinical Research Network, using traditional blinded adjudication as the gold standard., Methods: A total of 15 076 participants with established atherosclerotic cardiovascular disease were randomized to two doses of aspirin (81 mg and 325 mg once daily). Nonfatal end points (hospitalization for nonfatal myocardial infarction, nonfatal stroke, and major bleeding requiring transfusion of blood products) were captured with the use of programming algorithms applied to National Patient-Centered Clinical Research Network data. A random subset of end points was independently reviewed by a disease-specific expert adjudicator. The positive predictive value of the programming algorithms were calculated separately for end points listed as primary and as nonprimary diagnoses., Results: A total of 225 end points were identified (91 myocardial infarction events, 89 stroke events, and 45 bleeding events), including 142 (63%) that were listed as primary diagnoses. Complete source documents were missing for 14% of events. The positive predictive value were 90%, 72%, and 93% for hospitalizations for myocardial infarction, stroke, and major bleeding, respectively, as compared to adjudication. When only primary diagnoses were considered, positive predictive value were 93%, 91%, and 97%, respectively. When only nonprimary diagnoses were considered, positive predictive value were 82%, 36%, and 71%., Conclusions: As compared with blinded adjudication, clinical end point ascertainment from queries of the National Patient-Centered Clinical Research Network distributed harmonized data was valid to identify hospitalizations for myocardial infarction in ADAPTABLE. The proportion of contradicted events was high for hospitalizations for bleeding and strokes when nonprimary diagnoses were analyzed, but not when only primary diagnoses were considered.

Background: Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited., Methods: We performed an observational study using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights., Results: Our analytic sample included 123 186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable model, there was no association between EPD use and in-hospital stroke (adjusted relative risk, 0.90 [95% CI, 0.68-1.13]; absolute risk difference, -0.15% [95% CI, -0.49 to 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]; absolute risk difference, -0.28% [95% CI, -0.52 to -0.03]). Results were generally consistent across the secondary end points, as well as subgroup analyses., Conclusions: In this nationally representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary instrumental variable analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.

Objectives: This study sought to better understand out-of-hospital 30-day mortality following transfemoral transcatheter aortic valve replacement (TAVR) and identify factors associated with poor outcomes., Background: Despite improvements in outcomes with TAVR for severe aortic stenosis, out-of-hospital 30-day mortality has not been evaluated., Methods: This study examined patients in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry undergoing TAVR for severe aortic stenosis from January 2015 to March 2018. Primary and secondary endpoints were 30-day out-of-hospital all-cause mortality and out-of-hospital cardiovascular mortality, respectively. Logistic regression models were used to assess association between pre-specified factors and endpoints., Results: A total of 106,749 patients underwent TAVR and were eligible for analysis. Transfemoral TAVR was performed in 92.3% of patients. A total of 2,137 (2.2%) transfemoral patients died within 30 days of the procedure, and 623 (29%) patients of these patients experienced out-of-hospital 30-day mortality. Cardiovascular and pulmonary etiologies accounted for the majority of observed mortality. Multivariable regression analysis identified older age, gender, lower body surface area, lower left ventricular ejection fraction, lower hemoglobin, atrial fibrillation or flutter, severe lung disease, home oxygen use, lack of moderate-to-severe aortic insufficiency, urgent TAVR, lower Kansas City Cardiomyopathy Questionnaire score, longer hospital length of stay, and in-hospital complications as being independently associated with the primary endpoint. New onset or pre-existent atrial fibrillation or flutter was also independently associated with 30-day out-of-hospital cardiovascular mortality in the transfemoral population., Conclusions: We identified 30-day all-cause mortality rate for TAVR of 2.2%. Approximately one-third of patients experienced out-of-hospital mortality at 30 days. Several factors were identified as being independently associated with 30-day out-of-hospital all-cause and cardiovascular mortality. Further work is needed to understand how best to improve out-of-hospital mortality following TAVR., Competing Interests: Funding Support and Author Disclosures Dr. Anwaruddin has served on the advisory board for Medtronic and OpSens; has received speaking fees from Medtronic, Edwards Lifesciences, and Siemens; received consulting fees from Edwards Lifesciences; has served as a proctor/consultant for V wave; received institutional research support from the Cardiothoracic Surgery Network; and is on the Steering Committee for Boston Scientific. Dr. Desai has served as a speaker or consultant for Gore and Medtronic. Dr. Vemulapalli has served on the advisory board or as a consultant for Boston Scientific, HeartFlow, Baylabs (Caption Health), Janssen, and American College of Physicians; and has received grants or contracts from Abbott Vascular, Boston Scientific, the National Institutes of Health, Patient-Centered Outcomes Research, Nest (Food and Drug Administration), the American College of Cardiology, and the Society of Thoracic Surgeons. Dr. Marquis-Gravel has received grant support from the Canadian Institute of Health Sciences; and has received honoraria from Servier and Novartis. Dr. Reardon has served on the advisory board for Medtronic and Boston Scientific; and has served as a consultant for Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic "Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)" randomized trial that required a reappraisal of the IRB submission, review, and approval processes are discussed., Main Text: ADAPTABLE is a pragmatic, multicenter, open-label RCT evaluating the comparative effectiveness of two doses of aspirin widely used for secondary prevention (81 mg and 325 mg) in 15,000 patients with an established history of atherosclerotic cardiovascular disease. The electronic informed consent form is completed online by the participants at the time of enrollment, and endpoint ascertainment is conducted through queries of electronic health records. IRB challenges encountered regarding centralized IRB evaluation, electronic informed consent, patient engagement, and risk determination in ADAPTABLE are described in this manuscript. The experience of ADAPTABLE encapsulates how pragmatic protocol components intended to facilitate the study conduct have been tempered by unexpected, yet justified concerns raised by local IRBs. How the lessons learned can be applied to future similar pragmatic trials is delineated., Conclusion: Development of engaging communication channels between IRB and study personnel in pragmatic randomized trials as early as at the time of protocol design allows to reduce issues with IRB approval. Integrations of the lessons learned in ADAPTABLE regarding the IRB process for centralized IRBs, informed consent, patient engagement, and risk determination can be emulated and will be instrumental in future pragmatic studies.

Background: The current Canadian Cardiovascular Society antiplatelet therapy guidelines recommend the use of ticagrelor or prasugrel over clopidogrel as first-line platelet P2Y12 receptor antagonists for treatment of moderate- to high-risk acute coronary syndromes. Recently, Effient (prasugrel [Eli Lilly Canada Inc, Toronto, Canada]) was discontinued by its distributor in Canada., Methods: Five members of the Canadian Cardiovascular Society antiplatelet therapy 2018 guidelines committee undertook an independent, evidence-based review to outline patients for whom prasugrel should be the optimal P2Y12 agent and discuss alternative strategies to consider without prasugrel., Results: Several clinical scenarios where prasugrel should be indicated are identified and discussed. Considerations to be undertaken for alternative therapies are summarized, including a review of national and international guidelines for de-escalation of P2Y12 receptor antagonists., Conclusions: The discontinuation of prasugrel poses a challenge for clinicians. Clinicians must consider key factors in determining the best alternate therapy., (© 2021 The Authors.)

Competing Interests: Dr. Carcillo receives grant funding from the National Institute of General Medical Sciences (R01GM108618). The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: Longitudinal bleeding risk scores have been validated in patients treated with dual antiplatelet therapy (DAPT) following percutaneous coronary intervention. How these scores apply to the population of patients with acute coronary syndrome (ACS) treated without revascularization remains unknown. The objective was to evaluate and compare the performances of the PRECISE-DAPT, PARIS, and DAPT (bleeding component) bleeding risk scores in the medically managed patients with ACS treated with DAPT., Methods and Results: TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) was a double-blind, placebo-controlled randomized trial conducted from 2008 to 2012 over a median follow-up of 17.0 months in 966 sites (52 countries). High-risk patients with unstable angina or non-ST-segment-elevation myocardial infarction who did not undergo revascularization were randomized to prasugrel or clopidogrel. The PRECISE-DAPT, PARIS, and DAPT (bleeding component) risk scores were applied in the TRILOGY ACS population to evaluate their performance to predict adjudicated non-coronary artery bypass grafting-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe/life-threatening/moderate and TIMI (Thrombolysis in Myocardial Infarction) major/minor bleeding with time-dependent c-indices. Among the 9326 participants, median age was 66 years (interquartile range, 59-74 years), and 3650 were females (39.1%). A total of 158 (1.69%) GUSTO severe/life-threatening/moderate and 174 (1.87%) TIMI major/minor non-coronary artery bypass grafting bleeding events occurred. The c-indices (95% CI) of the PRECISE-DAPT, PARIS, and DAPT (bleeding component) scores through 12 months were 0.716 (0.677-0.758), 0.693 (0.658-0.733), and 0.674 (0.637-0.713), respectively, for GUSTO bleeding and 0.624 (0.582-0.666), 0.612 (0.578-0.651), and 0.608 (0.571-0.649), respectively, for TIMI bleeding. There was no significant difference in the c-indices of each score based upon pairwise comparisons., Conclusions: Among medically managed patients with ACS treated with DAPT, the performances of the PRECISE-DAPT, PARIS, and DAPT (bleeding component) scores were reasonable and similar to their performances in the derivation percutaneous coronary intervention populations. Bleeding risk scores may be used to predict longitudinal bleeding risk in patients with ACS treated with DAPT without revascularization and help support shared decision making. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00699998.

The role of percutaneous coronary interventions in addition to medical therapy for patients with stable coronary artery disease continues to be debated in routine clinical practice, despite more than 2 decades of randomized controlled trials. The residual uncertainty arises from particular challenges facing revascularization trials. Which endpoint do doctors care about, and which do patients care about? Which participants should be enrolled? What background medical therapy should we use? When is placebo control relevant? In this paper, we discuss how these questions can be approached and examine the merits and disadvantages of possible options. Engaging multiple stakeholders, including patients, researchers, regulators, and funders, to ensure the design elements are methodologically valid and clinically meaningful should be an aspirational goal in the development of future trials., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background: The long-term prognostic impact of post-discharge bleeding in the unique population of patients with acute coronary syndrome (ACS) treated without percutaneous coronary intervention (PCI) remains unexplored., Objectives: The aim of this study was to assess the association between post-discharge bleeding and subsequent mortality after ACS according to index strategy (PCI or no PCI) and to contrast with the association between post-discharge myocardial infarction (MI) and subsequent mortality., Methods: In a harmonized dataset of 4 multicenter randomized trials (APPRAISE-2 [Apixaban for Prevention of Acute Ischemic Events-2], PLATO [Study of Platelet Inhibition and Patient Outcomes], TRACER [Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome], and TRILOGY ACS [Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes]), the association between post-discharge noncoronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate, severe, or life-threatening bleeding (landmark 7 days post-ACS) and subsequent all-cause mortality was evaluated in a time-updated Cox proportional hazards analysis. Interaction with index treatment strategy was assessed. Results were contrasted with risk for mortality following post-discharge MI., Results: Among 45,011 participants, 1,133 experienced post-discharge bleeding events (2.6 per 100 patient-years), and 2,149 died during follow-up. The risk for mortality was significantly higher <30 days (adjusted hazard ratio: 15.7; 95% confidence interval: 12.3 to 20.0) and 30 days to 12 months (adjusted hazard ratio: 2.7; 95% confidence interval: 2.1 to 3.4) after bleeding, and this association was consistent in participants treated with or without PCI for their index ACS (p for interaction = 0.240). The time-related association between post-discharge bleeding and mortality was similar to the association between MI and subsequent mortality in participants treated with and without PCI (p for interaction = 0.696)., Conclusions: Post-discharge bleeding after ACS is associated with a similar increase in subsequent all-cause mortality in participants treated with or without PCI and has an equivalent prognostic impact as post-discharge MI., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to examine variation in the use of conscious sedation (CS) for transcatheter aortic valve replacement (TAVR) across hospitals and over time and to evaluate outcomes of CS compared with general anesthesia (GA) using instrumental variable analysis, a quasi-experimental method to control for unmeasured confounding., Background: Despite increasing use of CS for TAVR, contemporary data on utilization patterns are lacking, and existing studies evaluating the impact of sedation choice on outcomes may suffer from unmeasured confounding., Methods: Among 120,080 patients in the TVT (Transcatheter Valve Therapy) Registry who underwent transfemoral TAVR between January 2016 and March 2019, the relationship between anesthesia choice and TAVR outcomes was evaluated using hospital proportional use of CS as an instrumental variable., Results: Over the study period, the proportion of TAVR performed using CS increased from 33% to 64%, and CS was used in a median of 0% and 91% of cases in the lowest and highest quartiles of hospital CS use, respectively. On the basis of instrumental variable analysis, CS was associated with decreases in in-hospital mortality (adjusted risk difference: 0.2%; p = 0.010) and 30-day mortality (adjusted risk difference: 0.5%; p < 0.001), shorter length of hospital stay (adjusted difference: 0.8 days; p < 0.001), and more frequent discharge to home (adjusted risk difference: 2.8%; p < 0.001) compared with GA. The magnitude of benefit for most endpoints was less than in a traditional propensity score-based approach, however., Conclusions: In contemporary U.S. practice, the use of CS for TAVR continues to increase, although there remains wide variation across hospitals. The use of CS for TAVR is associated with improved outcomes (including reduced mortality) compared with GA, although the magnitude of benefit appears to be less than in previous studies., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Percutaneous cardiovascular interventions have changed dramatically in recent years, and the impetus given by the rapid implementation of novel techniques and devices have been mirrored by a refinement of antithrombotic strategies for secondary prevention, which have been supported by a significant burden of evidence from clinical studies. In the current manuscript, we aim to provide a comprehensive, yet pragmatic, revision of the current available evidence regarding antithrombotic strategies in the domain of percutaneous cardiovascular interventions. We revise the evidence regarding antithrombotic therapy for secondary prevention in coronary artery disease and stent implantation, the complex interrelation between antiplatelet and anticoagulant therapy in patients undergoing percutaneous coronary intervention with concomitant atrial fibrillation, and finally focus on the novel developments in the secondary prevention after structural heart disease intervention. A special focus on treatment individualization is included to emphasize risk and benefits of each therapeutic strategy.

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.