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Importance: Correction of tricuspid regurgitation using tricuspid transcatheter edge-to-edge repair (T-TEER) in addition to guideline-directed optimized medical therapy (OMT) may improve clinical outcomes., Objective: To evaluate the efficacy of T-TEER + OMT vs OMT alone in patients with severe, symptomatic tricuspid regurgitation., Design, Setting, and Participants: Investigator-initiated, prospective, randomized (1:1) trial evaluating T-TEER + OMT vs OMT alone in adult patients with severe, symptomatic tricuspid regurgitation. The trial was conducted at 24 centers in France and Belgium (March 2021 to March 2023; latest follow-up in April 2024)., Intervention: Patients were randomized to T-TEER + OMT or OMT alone., Main Outcomes and Measures: The primary outcome was a composite clinical end point at 1 year comprising change in New York Heart Association class, change in patient global assessment, or occurrence of major cardiovascular events. Tricuspid regurgitation severity was the first of 6 secondary outcomes analyzed in a hierarchical closed-testing procedure, including Kansas City Cardiomyopathy Questionnaire (KCCQ) score, patient global assessment, and a composite outcome of all-cause death, tricuspid valve surgery, KCCQ score improvement, or time to hospitalization for heart failure., Results: Of 300 enrolled patients (mean age, 78 [SD, 6] years, 63.7% women), 152 were allocated to T-TEER + OMT and 148 to OMT alone. At 1 year, 109 patients (74.1%) in the T-TEER + OMT group had an improved composite score compared with 58 patients (40.6%) in the OMT-alone group. Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the OMT-alone group (P < .001). Mean overall KCCQ summary score at 1 year was 69.9 (SD, 25.5) for the T-TEER + OMT group and 55.4 (SD, 28.8) for the OMT-alone group (P < .001). The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08) (P < .001)., Conclusions and Relevance: T-TEER reduces tricuspid regurgitation severity and improves a composite score driven by improved patient-reported outcome measures in patients with severe, symptomatic tricuspid regurgitation., Trial Registration: ClinicalTrials.gov Identifier: NCT04646811.

Importance: In patients with acute myocardial infarction (MI), limited physiologic adaptation to acute anemia might lead to greater benefit from a liberal red blood cell (RBC) transfusion strategy. Data on such a possible benefit are lacking., Objectives: To compare acute anemia with chronic anemia and post-MI outcomes and estimate the differential effect of a restrictive RBC transfusion strategy compared with a liberal strategy on post-MI outcomes according to anemia acuity., Design, Setting, and Participants: A prespecified subgroup analysis of the Myocardial Ischemia and Transfusion (MINT) multicenter randomized clinical trial was conducted in 126 hospitals in 6 countries between April 26, 2017, and April 14, 2023, with 30-day follow-up and blinded adjudication of the primary outcome. The analysis included 3144 of 3504 MINT participants (89.7%) with acute MI, a hemoglobin (Hb) level less than 10 g/dL at randomization, and a first Hb measurement available on the day of or the day following hospital admission., Intervention: The MINT trial randomized participants to a restrictive (Hb <7-8 g/dL) or liberal (Hb <10 g/dL) RBC transfusion strategy. Acute anemia was defined as having a first Hb value greater than 13 g/dL (men) or 12 g/dL (women), or as having a decrease greater than or equal to 2 g/dL between the first Hb measurement and measurement at randomization. Other Hb levels were categorized as chronic anemia., Main Outcomes and Measures: The primary outcome was a composite of death or recurrent MI up to 30 days after randomization. Secondary outcomes were death, recurrent MI, cardiac death, heart failure, pulmonary complications, and major bleeding events. Intention-to-treat analysis was performed., Results: Among 3144 included participants (mean [SD] age, 72.3 [11.6] years; 1715 [54.5%] male; 1307 [41.6%] with type 1 MI), 1078 [34.3%]) had acute anemia. Acute anemia was associated with an increased risk of death or recurrent MI (adjusted risk ratio, 1.25; 95% CI, 1.05-1.48). The effect of a restrictive RBC transfusion strategy compared with a liberal strategy was similar for participants with either acute or chronic anemia for all outcomes., Conclusions and Relevance: In this secondary analysis of the MINT trial, acute anemia was associated with less favorable post-MI outcomes than chronic anemia but did not modify the effects of the randomized transfusion strategy. In patients with anemia and MI, the acuity of anemia should not influence the choice of transfusion trigger., Trial Registration: ClinicalTrials.gov Identifier: NCT02981407.

Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.

Detecting microsecond structural perturbations in biomolecules has wide relevance in biology, chemistry and medicine. Here we show how MHz repetition rates at X-ray free-electron lasers can be used to produce microsecond time-series of protein scattering with exceptionally low noise levels of 0.001%. We demonstrate the approach by examining Jɑ helix unfolding of a light-oxygen-voltage photosensory domain. This time-resolved acquisition strategy is easy to implement and widely applicable for direct observation of structural dynamics of many biochemical processes., (© 2024. The Author(s).)

Background: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI)., Methods: We used data from the randomized REALITY trial. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE): composite of all-cause death, nonrecurrent AMI, stroke, or emergency revascularization prompted by ischemia at 30 days., Results: Among 658 randomized patients, 311 (47.3%) had HF. Patients with HF had higher rates of MACE at 30 days and 1 year and higher rates of nonfatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or nonfatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF (P interaction  = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11)., Conclusions: HF is frequent in patients with AMI and anemia and is associated with higher risk of MACE (including all-cause death) and nonfatal new-onset HF. Although there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death caused by HF., Clinical Trial Registration: NCT02648113., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute heart failure (AHF) is a leading cause of hospitalization and mortality - especially in patients aged≥65 years in high-income countries - and represents a high healthcare burden. In the past decade, the epidemiology and management of heart failure (HF) has changed, with the emergence of new medical and interventional therapeutics, but up-to-date real-life data are scarce., Aims: The main objectives are to describe baseline characteristics (with an emphasis on lifestyle, cognitive status, HF knowledge and treatment adherence), management, and in-hospital and mid-term outcomes of AHF patients in France. Secondary objectives are to investigate determinants of prognosis, modalities of treatment and follow-up, and identify gaps between guidelines and real-life management., Methods: OFICA2 is a prospective multicentre observational survey that enrolled 1513 patients hospitalized for AHF in 80 participating centres in France during March and April 2021. The diagnosis of AHF was made according to the European Society of Cardiology guidelines definition. Inclusion criteria were age≥18years, health coverage and consent to participate. Detailed information was collected prospectively starting at admission. Thanks to direct linking with the French National Health Database, the anteriority up to 2years before inclusion, as well as a 3-year follow-up is specified for each patient and includes individual information on death, hospital admissions, major clinical events, drug delivery and use of reimbursed health resources., Conclusion: This cohort provides a representative snapshot on contemporary AHF, with a particular focus on self-care determinants, and will improve knowledge about AHF presentation, management and outcomes., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background and Aims: It has been reported that patients without standard modifiable cardiovascular (CV) risk factors (SMuRFs-diabetes, dyslipidaemia, hypertension, and smoking) presenting with first myocardial infarction (MI), especially women, have a higher in-hospital mortality than patients with risk factors, and possibly a lower long-term risk provided they survive the post-infarct period. This study aims to explore the long-term outcomes of SMuRF-less patients with stable coronary artery disease (CAD)., Methods: CLARIFY is an observational cohort of 32 703 outpatients with stable CAD enrolled between 2009 and 2010 in 45 countries. The baseline characteristics and clinical outcomes of patients with and without SMuRFs were compared. The primary outcome was a composite of 5-year CV death or non-fatal MI. Secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE-CV death, non-fatal MI, or non-fatal stroke)., Results: Among 22 132 patients with complete risk factor and outcome information, 977 (4.4%) were SMuRF-less. Age, sex, and time since CAD diagnosis were similar across groups. SMuRF-less patients had a lower 5-year rate of CV death or non-fatal MI (5.43% [95% CI 4.08-7.19] vs. 7.68% [95% CI 7.30-8.08], P = 0.012), all-cause mortality, and MACE. Similar results were found after adjustments. Clinical event rates increased steadily with the number of SMuRFs. The benefit of SMuRF-less status was particularly pronounced in women., Conclusions: SMuRF-less patients with stable CAD have a substantial but significantly lower 5-year rate of CV death or non-fatal MI than patients with risk factors. The risk of CV outcomes increases steadily with the number of risk factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important., Aims: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period., Methods: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies., Conclusions: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up., Methods: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577)., Results: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P =0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively., Conclusions: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954., Competing Interests: Disclosures None.

Background: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown., Objectives: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial., Methods: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel., Results: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (P interaction  = 0.47) nor the secondary endpoints., Conclusions: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel., Competing Interests: Funding Support and Author Disclosures The ALPHEUS trial was led by the ACTION Study Group, an academic research organization based at the Pitié-Salpêtrière Hospital (Paris, France). The study was sponsored by Assistance Publique-Hopitaux de Paris and was funded by an unrestricted grant from AstraZeneca. The present work was supported by a grant of the French Federation of Cardiology. Prof Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi Sankyo, Fédération Française de Cardiologie, and the Institute of CardioMetabolism and Nutrition; consulting fees from Daiichi Sankyo and Eli Lilly; and lecture fees from AstraZeneca, Medtronic, and Novartis. Prof Cayla has received consulting fees from Edwards Lifesciences, Medtronic, and Microport CRM; and lecture fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport, Medtronic, Pfizer, and Sanofi. Prof Ducrocq has received speaker and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Novo Nordisk, and Sanofi; has served on steering committees for Amgen, Novo Nordisk, and Janssen; and has been a proctor for Boston Scientific. Dr Laredo has received speaker or consulting fees from Abbott and Biotronik. Dr Kala has received consulting fees from Boston Scientific; and lecture fees from AstraZeneca, Edwards Lifesciences, Novartis, Servier, and Terumo. Prof Varenne has received research grants from Abbott and Boston Scientific; and lecture fees from Abbott, AstraZeneca, Boston Scientific, and Servier. Prof Spaulding has received consulting fees from Edwards Lifesciences, Medtronic, Sonivie, Techwald, and Valcare; has received speaker fees from Amgen and Edwards Lifesciences; and is stock shareholder of Techwald and Valcare. Prof Beygui has received consulting and lecture fees from Medtronic, Novartis, and Pfizer; and research grants from Biosensors and Medtronic. Dr Rangé has received speaker or consulting fees from Abbott and Microport. Prof Vicaut has received consulting or speaker fees from Abbott, Amgen, Bristol Myers Squibb, Celgene, LFB, Pfizer, and Sanofi. Prof Collet has received consulting and lecture fees from AstraZeneca, Boston Scientific, Bristol Myers Squibb, COR2ED, Lead-Up, Medtronic, and WebMD. Prof Montalescot has received research grants and consulting or speaker fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Prof Silvain has received research grants and consulting or speaker fees from AstraZeneca, Bayer HealthCare SAS, Abbott Medical, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, and Sanofi France; and is stock Shareholder of Pharmaseeds, Terumo, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Data on new-onset atrial fibrillation (NOAF) in patients with chronic coronary syndromes (CCS) are scarce. This study aims to describe the incidence, predictors, and impact on cardiovascular (CV) outcomes of NOAF in CCS patients., Methods: Data from the international (45 countries) CLARIFY registry (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) were used. Among 29 001 CCS outpatients without previously reported AF at baseline, patients with at least one episode of AF/flutter diagnosed during 5-year follow-up were compared with patients in sinus rhythm throughout the study., Results: The incidence rate of NOAF was 1.12 [95% confidence interval (CI) 1.06-1.18] per 100 patient-years (cumulative incidence at 5 years: 5.0%). Independent predictors of NOAF were increasing age, increasing body mass index, low estimated glomerular filtration rate, Caucasian ethnicity, alcohol intake, and low left ventricular ejection fraction, while high triglycerides were associated with lower incidence. New-onset atrial fibrillation was associated with a substantial increase in the risk of adverse outcomes, with adjusted hazard ratios of 2.01 (95% CI 1.61-2.52) for the composite of CV death, non-fatal myocardial infarction, or non-fatal stroke, 2.61 (95% CI 2.04-3.34) for CV death, 1.64 (95% CI 1.07-2.50) for non-fatal myocardial infarction, 2.27 (95% CI 1.85-2.78) for all-cause death, 8.44 (95% CI 7.05-10.10) for hospitalization for heart failure, and 4.46 (95% CI 2.85-6.99) for major bleeding., Conclusions: Among CCS patients, NOAF is common and is strongly associated with worse outcomes. Whether more intensive preventive measures and more systematic screening for AF would improve prognosis in this population deserves further investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Left atrial appendage closure (LAAC) is recommended to decrease the stroke risk in patients with atrial fibrillation and contraindications to anticoagulation. However, age-stratified data are scarce. The aim of this study was to provide information on the safety and efficacy of LAAC, with emphasis on the oldest patients., Methods: A nationwide, prospective, multicentre, observational registry was established by 53 French cardiology centres in 2018-2021. The composite primary endpoint included ischaemic stroke, systemic embolism, and unexplained or cardiovascular death. Separate analyses were done in the groups <80 years and ≥80 years., Results: Among the 1053 patients included, median age was 79.7 (73.6-84.3) years; 512 patients (48.6%) were aged ≥80 years. Procedure-related serious adverse events were non-significantly more common in octogenarians (7.0% vs 4.4% in patients aged <80 years, respectively; p=0.07). Despite a higher mean CHA 2 DS 2 -VASc score in octogenarians, the rate of thromboembolic events during the study was similar in both groups (3.0 vs 3.1/100 patient-years; p=0.85). By contrast, all-cause mortality was significantly higher in octogenarians (15.3 vs 10.1/100 patient-years, p<0.015), due to a higher rate of non-cardiovascular deaths (8.2 vs 4.9/100 patient-years, p=0.034). The rate of the primary endpoint was 8.1/100 patient-years overall with no statistically significant difference between age groups (9.4 and 7.0/100 patient-years; p=0.19)., Conclusion: Despite a higher mean CHA 2 DS 2 -VASc score in octogenarians, the rate of thromboembolic events after LAAC in this age group was similar to that in patients aged <80 years., Trial Registration Number: ClinicalTrials.gov Registry (NCT03434015)., Competing Interests: Competing interests: ET and PLC received unrestricted research grants from Boston Scientific and St Jude Medical for this study. PG is the medical director and shareholder of CERC (Cardiovascular European Research Center) and received speaker’s and advisory fees from Abbott and Boston Scientific. GR is proctor for Boston Scientific. RE is consultant and has performed proctoring for Boston Scientific and Abbott. None for all other authors., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are dated and conflicting data about the optimal timing of initiation of P2Y 12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y 12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y 12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI., Methods: The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury)., Results: Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups., Conclusions: In elective PCI, administration of the oral P2Y 12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)