ApoA-I Infusions and Burden of Ischemic Events After Acute Myocardial Infarction: Insights From the AEGIS-II Trial.

BACKGROUND: Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90 days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events. OBJECTIVES: This prespecified exploratory analysis examines the effect of CSL112 on total burden of nonfatal ischemic events (ie, recurrent MI and stroke) and CV death. METHODS: A total of 18,219 patients with AMI, multivessel coronary artery disease, and additional CV risk factors were randomized to either 4 weekly infusions of 6 g CSL112 (n = 9,112) or matching placebo (n = 9,107). A negative binomial regression model was applied to estimate the effect of CSL112 compared with placebo on the rate ratio (RR) of ischemic events. RESULTS: For CV death, MI, and stroke, there were numerically fewer total events at 90 days (503 vs 545 events; rate ratio [RR]: 0.88; 95% CI: 0.76-1.03, P = 0.11), and nominally significantly fewer total events at 180 days (745 vs 821 events, RR: 0.87; 95% CI: 0.77-0.99; P = 0.04) and 365 days (1,120 vs 1,211 events; RR 0.89; 95% CI: 0.80-0.99; P = 0.04). Subsequent events constituted 13% of events at 90 days, 17% at 180 days, and 22% at 1 year. Similar findings were seen with the total occurrence of nonfatal MI and CV death. When type II MIs, unlikely to be modified by enhancing cholesterol efflux, were excluded, there were nominally significant reductions in the total occurrence of nonfatal MI (excluding type 2) and CV death at all timepoints (90 days: RR: 0.81; 95% CI: 0.68-0.97; P = 0.02; 180 days: RR: 0.82; 95% CI: 0.71-0.95; P < 0.01; 365 days: RR: 0.86; 95% CI: 0.76-0.98; P = 0.02). CONCLUSIONS: In this prespecified exploratory analysis of the AEGIS-II trial, 4 weekly infusions of CSL112 among high-risk patients after AMI significantly reduced the total burden of nonfatal ischemic events and CV death at 180 and 365 days compared with placebo. (AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome]; NCT03473223).

Apolipoprotein A-I Infusions and Cardiovascular Outcomes in Acute Myocardial Infarction According to Baseline LDL-Cholesterol Levels: The AEGIS-II Trial.

BACKGROUND AND AIMS: In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days versus placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C. METHODS: Overall, 18,219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n=15,731). RESULTS: As baseline LDL-C increased, risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days (hazard ratio 0.69 [0.53-0.90], 0.71 [0.57-0.88], and 0.78 [0.65-0.93]). In contrast, there was no difference between treatment groups among those with LDL-C <100 mg/dL at baseline. CONCLUSIONS: In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.

Potent P2Y12 Inhibitor Selection and De-escalation Strategies in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: Systematic Review and Meta-analysis.

Background: Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent purinergic receptor type Y, subtype 12 (P2Y12) 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) P2Y12 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 P2Y12 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 P2Y12 inhibitor was associated with a decrease in incidence of major bleeding without increasing thrombotic outcomes in ACS patients post-percutaneous coronary intervention.

Contexte: Équilibrer les effets de la bithérapie antiplaquettaire (BTAP) à l'ère des puissants inhibiteurs du récepteur purinergique de type Y, sous-type 12 (P2Y12) demeure un défi dans la prise en charge du syndrome coronarien aigu (SCA). Méthodologie: Nous avons procédé à un examen systématique et à une méta-analyse, tout d'abord en recherchant les revues systématiques publiées entre 2019 et 2022, puis en mettant à jour la recherche la plus complète de ces revues jusqu'en novembre 2022. Nous avons inclus des essais contrôlés randomisés (ECR) menés chez des patients ayant subi un SCA traité par intervention coronarienne percutanée qui comparaient i) une BTAP comportant du ticagrélor à une BTAP à base de prasugrel, et ii) les stratégies de réduction graduelle de la dose de l'inhibiteur de P2Y12. Les résultats d'intérêt comprenaient les événements cardiovasculaires indésirables majeurs (ECIM), les décès toutes causes confondues, les thromboses de l'endoprothèse et les saignements majeurs. Nous avons estimé les rapports de risques (RR) et les intervalles de confiance (IC) à 95 % à l'aide d'un modèle à effets aléatoires. Résultats: Huit ECR (n = 5 571) ont comparé le ticagrélor au prasugrel. Le ticagrélor était associé à un risque accru d'ECIM comparativement au prasugrel (RR de 1,23, IC à 95 % de 1,01 à 1,49, certitude modérée), sans différence significative quant au décès, à la thrombose de l'endoprothèse ou au saignement majeur. Dans deux ECR (n = 3 343) comparant la réduction graduelle de la BTAP à base de clopidogrel après 1 mois à la poursuite de la BTAP comportant un inhibiteur puissant de P2Y12, la réduction graduelle de la dose de clopidogrel n'a pas modifié de manière significative la fréquence des ECIM, des décès ou des thromboses de l'endoprothèse, mais a réduit celle des saignements majeurs (RR de 0,51, IC à 95 % de 0,28 à 0,92, certitude élevée). L'effet de la réduction graduelle de la dose de prasugrel n'a pas été concluant pour tous les résultats sur la base d'un seul essai. Conclusions: Si l'on se fie aux données probantes de faible certitude, le ticagrélor a été associé à une augmentation des ECIM comparativement au prasugrel, tandis que la réduction graduelle de la dose de clopidogrel après 1 mois d'administration d'un puissant inhibiteur de P2Y12 a été associée à une diminution de la fréquence des saignements majeurs sans augmentation des événements thrombotiques chez les patients ayant subi une intervention coronarienne percutanée pour traiter un SCA.

Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Disease With Recent or Remote Events: Systematic Review and Meta-analysis.

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.

Contexte: La question du traitement antithrombotique optimal chez les personnes présentant une fibrillation auriculaire (FA) et une coronaropathie demeure controversée. Méthodologie: Nous avons réalisé une revue systématique et une méta-analyse pour synthétiser les essais contrôlés randomisés ayant comparé i) la bithérapie (anticoagulant oral et antiplaquettaire) et la trithérapie (anticoagulant oral et bithérapie antiplaquettaire) après une intervention coronarienne percutanée (ICP) ou un syndrome coronarien aigu (SCA), et ii) un anticoagulant oral en monothérapie et la bithérapie au moins 1 an après une ICP ou un SCA. Nous avons procédé en 2 temps, d'abord en répertoriant les revues systématiques publiées entre 2019 et 2022 sur ces 2 questions cliniques, puis en effectuant la recherche la plus exhaustive possible pour trouver d'autres essais contrôlés randomisés publiés jusqu'en octobre 2022. Les paramètres qui nous intéressaient étaient les événements cardiovasculaires indésirables majeurs (ECIM), le décès, la thrombose de l'endoprothèse et l'hémorragie majeure. Nous avons estimé les rapports de risques (RR) et les intervalles de confiance (IC) à 95 % à l'aide d'un modèle à effets aléatoires. Résultats: D'après 6 essais contrôlés randomisés (n = 10 435), la bithérapie a réduit les hémorragies majeures (RR : 0,62; IC à 95 % : 0,52 à 0,73) et augmenté les thromboses de l'endoprothèse (RR : 1,55; IC à 95 % : 1,02 à 2,36), comparativement à la trithérapie après une ICP ou un SCA ayant fait l'objet d'une prise en charge médicale, tandis qu'aucune différence significative n'a été observée quant aux ECIM et aux décès. Dans 2 essais contrôlés randomisés (n = 2 905), un anticoagulant oral en monothérapie a réduit les hémorragies majeures (RR : 0,66; IC à 95 % : 0,49 à 0,91) comparativement à la bithérapie chez des patients présentant une FA après une ICP ou un SCA plus lointain, sans différence significative quant aux ECIM et aux décès. Conclusions: Chez les patients présentant une FA et une coronaropathie, l'utilisation d'un traitement antithrombotique moins agressif (bithérapie après un ICP ou un SCA, et anticoagulant oral en monothérapie après une ICP ou un SCA plus lointain) réduit les hémorragies majeures, mais s'accompagne d'une augmentation des thromboses de l'endoprothèse en cas d'ICP récente. Ces résultats plaident en faveur d'une stratégie antithrombotique minimaliste, mais personnalisée chez ces patients.

Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI.

BACKGROUND: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI. OBJECTIVES: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI. METHODS: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo. RESULTS: The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis). CONCLUSIONS: Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.

Outcomes of management strategies in patients with prior coronary artery bypass grafting presenting with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass grafting (CABG) presenting with an acute coronary syndrome (ACS) have poor outcomes and the optimal treatment strategy for this population is unknown. METHODS: Using linked administrative databases, we examined patients with an ACS between 2008 and 2019, identifying patients with prior CABG. Patients were categorized by ACS presentation type and treatment strategy. Our primary outcome was the composite of death and recurrent myocardial infarction at one year. RESULTS: Of 54,641 patients who presented with an ACS, 1670 (3.1%) had a history of prior CABG. Of those, 11.0% presented with an ST-elevation myocardial infarction (STEMI) of which, 15.3% were treated medically, 31.1% underwent angiography but were treated medically, 22.4% with fibrinolytic therapy and 31.1% with primary PCI. The primary outcome rate was the highest (36.8%) in patients who did not undergo angiography and was similar in the primary PCI (20.8%) and fibrinolytic group (21.9%). In patients presenting with a non-ST elevation acute coronary syndrome (NSTE-ACS) (89.0%), 33.2% were treated medically, 38.5% underwent angiography but were treated medically and 28.2% were treated with PCI. Compared to those who underwent PCI, patients treated conservatively demonstrated a higher risk of the composite outcome (14.8% vs 27.3%; adjusted hazard ratio 1.70, 95% confidence interval 1.22-2.37). CONCLUSIONS: Patients with prior CABG presenting with an ACS are often treated conservatively without PCI, which is associated with a higher risk of adverse events.

Applicability and impact of the COMPASS trial in a Canadian population of patients with atherosclerotic disease.

BACKGROUND AND AIMS: In the COMPASS trial, low-dose rivaroxaban with aspirin improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the potential clinical implications of this therapy in a generalizable population. METHODS AND RESULTS: A retrospective cohort of adults with ASVCD was formed using healthcare administrative databases in Alberta, Canada (population 4.4 million). Patients with a new diagnosis between 2008 and 2019 formed the epidemiological cohort (n = 224,600) and those with long-term follow-up (>5 years) formed the outcomes cohort (n = 232,460). The primary outcome of major adverse cardiovascular events (MACE) was assessed and categorized based on the COMPASS trial eligibility. In the outcomes cohort, 77% had only coronary artery disease, 15% had only peripheral artery disease, and 8% had both. Of those, 37% met the COMPASS trial eligibility criteria, 36% met exclusion criteria and 27% did not meet inclusion criteria. Over a median of 7.8 years, the COMPASS exclusion group demonstrated the highest rate of MACE (5.9 per 100 person-years), following by the eligible group and the group that did not meet COMPASS inclusion criteria (3.1 and 1.4 per 100 person-years respectively). The expected net clinical benefit of antithrombotic therapy in the eligible group was 5.6 fewer events per 1000 person-years. CONCLUSIONS: In a real-world population of 4.4 million adults, there are roughly 20,000 new cases of ASVCD diagnosed yearly, with ∼40% being eligible for the addition of low-dose rivaroxaban therapy to antiplatelet therapy. The theoretical implementation of dual antithrombotic treatment in this population could result in a substantial reduction in cardiovascular morbidity and mortality.

Reperfusion in Patients With ST-Segment-Elevation Myocardial Infarction With Cardiogenic Shock and Prolonged Interhospital Transport Times.

BACKGROUND: In patients with ST-segment-elevation myocardial infarction complicated by cardiogenic shock, primary percutaneous coronary intervention (pPCI) is the preferred revascularization option. Little is known about the efficacy and safety of a pharmacoinvasive approach for patients with cardiogenic shock presenting to a non-PCI hospital with prolonged interhospital transport times. METHODS: In a retrospective analysis of geographically extensive ST-segment-elevation myocardial infarction network (2006-2021), 426 patients with cardiogenic shock and ST-segment-elevation myocardial infarction presented to a non-PCI-capable hospital and underwent reperfusion therapy (53.8% pharmacoinvasive and 46.2% pPCI). The primary clinical outcome was a composite of in-hospital mortality, renal failure requiring dialysis, cardiac arrest, or mechanical circulatory support, and the primary safety outcome was major bleeding defined as an intracranial hemorrhage or bleeding that required transfusion was compared in an inverse probability weighted model. The electrocardiographic reperfusion outcome of interest was the worst residual ST-segment-elevation. RESULTS: Patients with pharmacoinvasive treatment had longer median interhospital transport (3 hours versus 1 hour) and shorter median symptom-onset-to-reperfusion (125 minute-to-needle versus 419 minute-to-balloon) times. ST-segment resolution ≥50% on the postfibrinolysis ECG was 56.6%. Postcatheterization, worst lead residual ST-segment-elevation <1 mm (57.3% versus 46.3%; P=0.01) was higher in the pharmacoinvasive compared with the pPCI cohort, but no differences were observed in the worst lead ST-segment-elevation resolution ≥50% (77.4% versus 81.8%; P=0.57). The primary clinical end point was lower in the pharmacoinvasive cohort (35.2% versus 57.0%; inverse probability weighted odds ratio, 0.44 [95% CI, 0.26-0.72]; P<0.01) compared with patients who received pPCI. An interaction between interhospital transfer time and reperfusion strategy with all-cause mortality was observed, favoring a pharmacoinvasive approach with transfer times >60 minutes. The incidence of the primary safety outcome was 10.1% in the pharmacoinvasive arm versus 18.7% in pPCI (adjusted odds ratio, 0.41 [95% CI, 0.14-1.09]; P=0.08). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction presenting with cardiogenic shock and prolonged interhospital transport times, a pharmacoinvasive approach was associated with improved electrocardiographic reperfusion and a lower rate of death, dialysis, or mechanical circulatory support without an increase in major bleeding.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

Effects of complete revascularization according to age in patients with ST-segment elevation myocardial infarction and multivessel disease (COMPLETE-AGE).

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown. METHODS: COMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only PCI. In this prespecified subgroup analysis, treatment effect according to age (≥65 years vs <65 years) was determined for the first coprimary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second coprimary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6-44.3 months). RESULTS: Of 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both coprimary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first coprimary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI, 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI, 0.54-0.96)(interaction P = .74). The second coprimary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI, 0.43-0.74) and < 65 years (HR 0.48, 95% CI, 0.37-0.61 (interaction P = .37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated). CONCLUSIONS: In patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology 2023 Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Psychosocial Factors of Women Presenting With Myocardial Infarction With or Without Obstructive Coronary Arteries.

BACKGROUND: Women with myocardial infarction (MI) are more likely to have elevated stress levels and depression than men with MI. OBJECTIVES: We investigated psychosocial factors in women with myocardial infarction with nonobstructive coronary arteries (MINOCA) and those with MI and obstructive coronary artery disease (CAD). METHODS: Women with MI enrolled in a multicenter study and completed measures of perceived stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-2) at the time of MI (baseline) and 2 months later. Stress, depression, and changes over time were compared between MI subtypes. RESULTS: We included 172 MINOCA and 314 MI-CAD patients. Women with MINOCA were younger (age 59.4 years vs 64.2 years; P < 0.001) and more diverse than those with MI-CAD. Women with MINOCA were less likely to have high stress (Perceived Stress Scale-4 ≥6) at the time of MI (51.0% vs 63.0%; P = 0.021) and at 2 months post-MI (32.5% vs 46.3%; P = 0.019) than women with MI-CAD. There was no difference in elevated depressive symptoms (Patient Health Questionnaire-2 ≥2) at the time of MI (36% vs 43%; P = 0.229) or at 2 months post-MI (39% vs 40%; P = 0.999). No differences in the rate of 2-month decline in stress and depression scores were observed between groups. CONCLUSIONS: Stress and depression are common among women at the time of and 2 months after MI. MINOCA patients were less likely to report high stress compared with MI-CAD patients, but the frequency of elevated depressive symptoms did not differ between the 2 groups. Stress and depressive symptoms decreased in both MI-CAD and MINOCA patients over time.

Short dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk patients: Systematic review and meta-analysis.

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.

STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02777580.

Comparative Analysis of Patients With STEMI and COVID-19 Between Canada and the United States.

Background: Important health care differences exist between the United States (US) and Canada, which may have been exacerbated during the pandemic. We compared clinical characteristics, treatment strategies, and clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 (STEMI-COVID) treated in the US and Canada. Methods: The North American COVID-19 Myocardial Infarction registry is a prospective, investigator-initiated study enrolling patients with STEMI with confirmed or suspected COVID-19 in the US and Canada. The primary end point was in-hospital mortality. Additionally, we explored associations between vaccination and clinical outcomes. Results: Of 853 patients with STEMI-COVID, 112 (13%) were enrolled in Canada, and compared with the US, patients in Canada were more likely to present with chest pain and less likely to have a history of heart failure, stroke/transient ischemic attack, pulmonary infiltrates or renal failure. In both countries, the primary percutaneous coronary intervention was the dominant reperfusion strategy, with no difference in door-to-balloon times; fibrinolysis was used less frequently in the US than in Canada. The adjusted in-hospital mortality was not different between the 2 countries (relative risk [RR], 1.0; 95% CI, 0.46-2.72; P = 1.0). However, the risk of in-hospital mortality was significantly higher in unvaccinated compared with vaccinated patients with STEMI-COVID (RR, 4.7; 95% CI, 1.7-11.53; P = .015). Conclusions: Notable differences in morbidities and reperfusion strategies were evident between patients with STEMI-COVID in the US compared with Canada. No differences were noted for in-hospital mortality. Vaccination, regardless of region, appeared to associate with a lower risk of in-hospital mortality strongly.

Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.