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.

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.

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.

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.

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.

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.

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.

Aspirin for the Primary Prevention of Vascular Ischemic Events: An Updated Systematic Review and Meta-analysis to Support Shared Decision-Making.

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.

Contexte: Depuis la publication, en 2010, des lignes directrices canadiennes sur les agents antiplaquettaires, plusieurs importants essais contrôlés randomisés (ECR) ont été menés pour évaluer le rôle de l'aspirine (AAS) en prévention primaire. Nous avons comparé l'effet de l'AAS à la non-utilisation de l'AAS sur les événements ischémiques et hémorragiques chez des patients présentant une maladie cardiovasculaire athéroscléreuse (MCVAS) connue. Méthodologie: Nous avons mis à jour une revue systématique et une méta-analyse déjà publiées en effectuant une recherche dans les bases de données MEDLINE, Embase et CENTRAL jusqu'en mars 2023. Nous avons inclus les ECR ayant porté sur la prévention primaire de la MCVAS chez les patients et comparé l'AAS et la non-utilisation de l'AAS. Nous avons évalué le risque de biais à l'aide de l'outil RoB de Cochrane, et le degré de certitude des données probantes au moyen des critères GRADE. Le principal critère d'évaluation de l'efficacité était les événements cardiovasculaires indésirables majeurs (ECIM; décès, infarctus du myocarde ou accident vasculaire cérébral). Les principaux critères d'évaluation de l'innocuité étaient les hémorragies intracrâniennes (HIC) et les saignements extracrâniens majeurs (SECM). Nous avons utilisé un modèle à effets aléatoires afin de générer les rapports de risque (RR) et les intervalles de confiance (IC) à 95 % regroupés. Résultats: Nous avons inclus 14 ECR (n = 167 587) associés à un faible risque de biais et dont le suivi médian était de 5 ans. Comparativement à la non-utilisation d'AAS, l'AAS a réduit les ECIM (RR : 0,90; IC à 95 % : 0,86-0,94), mais était associé à un risque plus élevé d'HIC (RR : 1,33; IC à 95 % : 1,13-1,56) et de SECM (RR : 1,67; IC à 95 % : 1,36-2,06). Les estimations de l'effet étaient constantes dans les sous-groupes définis au préalable selon l'âge, le sexe et le diabète. Conclusion: En prévention primaire, l'AAS est associé à une réduction systématique des ECIM, mais au détriment de manifestations hémorragiques majeures. Les valeurs et les préférences du patient doivent être prises en compte lorsqu'on envisage l'AAS en prévention primaire.

Complete Revascularization vs Culprit Lesion-Only Percutaneous Coronary Intervention for Angina-Related Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction: Results From the COMPLETE Randomized Clinical Trial.

Importance: In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown. Objective: To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD. Design, Setting, and Participants: This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021. Interventions: Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization. Main Outcomes and Measures: Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end. Results: Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02). Conclusions and Relevance: In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.

Cardiovascular and Renal Implications of Myocardial Infarction in the ISCHEMIA-CKD Trial.

BACKGROUND: ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) reported an initial invasive treatment strategy did not reduce the risk of death or nonfatal myocardial infarction (MI) compared with a conservative treatment strategy in patients with advanced chronic kidney disease, stable coronary disease, and moderate or severe myocardial ischemia. The cumulative frequency of different MI type after randomization and subsequent prognosis have not been reported. METHODS: MI classification was based on the Third Universal Definition for MI. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary MI definition used cTn (cardiac troponin); both definitions included elevated biomarker-only events with higher thresholds than nonprocedural MIs. The cumulative frequency of MI type according to treatment strategy was determined. The association of MI with subsequent all-cause death and new dialysis initiation was assessed by treating MI as a time-dependent covariate. RESULTS: The 3-year incidence of type 1 or 2 MI with the primary MI definition was 11.2% in invasive treatment strategy and 13.6% in conservative treatment strategy (hazard ratio [HR], 0.66 [95% CI, 0.42-1.02]). Procedural MIs were more frequent in invasive treatment strategy and accounted for 9.8% and 28.3% of all MIs with the primary and secondary MI definitions, respectively. Patients had an increased risk of all-cause death after type 1 MI (adjusted HR, 4.35 [95% CI, 2.73-6.93]) and after procedural MI with the primary (adjusted HR, 2.75 [95% CI, 0.99-7.60]) and secondary MI definitions (adjusted HR, 2.91 [95% CI, 1.73-4.88]). Dialysis initiation was increased after a type 1 MI (HR, 6.45 [95% CI, 2.59-16.08]) compared with patients without an MI. CONCLUSIONS: In ISCHEMIA-CKD, the invasive treatment strategy had higher rates of procedural MIs, particularly with the secondary MI definition, and lower rates of type 1 and 2 MIs. Procedural MIs, type 1 MIs, and type 2 MIs were associated with increased risk of subsequent death. Type 1 MI increased the risk of dialysis initiation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01985360.

The Evolution of Anticoagulation for Percutaneous Coronary Intervention: A 40-Year Journey.

The selection of antithrombotic strategies continue to be of utmost importance during percutaneous coronary intervention (PCI) and have evolved over the past 40 years. Although the backbone of therapy during PCI continues to be a combination of oral antiplatelets and parenteral anticoagulants, a variety of different approaches have been tested over time. In particular, different choices of anticoagulation management have been tested in the stable ischemic heart disease and acute coronary syndrome setting. Evaluation of alternative regimens in the quest to balance ischemic and bleeding risk have undoubtedly improved patient care with PCI. In the current review we highlight the evolution of evidence-based therapeutic options over the past 40 years from the beginning of coronary angioplasty to contemporary PCI. We provide insight into future therapeutic options and provide a contemporary overview of anticoagulation choices for patients who require PCI on the basis of up-to-date evidence balancing ischemic and bleeding risk and according to clinical presentation.