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Background: Patients experiencing myocardial infarction (MI) remain at high risk of future major adverse cardiovascular events (MACE). While low-dose colchicine and spironolactone have been shown to decrease post-MI MACE, more data are required to confirm their safety and efficacy in an unselected post-MI population. Therefore, we initiated the CLEAR SYNERGY (OASIS 9) trial to address these uncertainties., Methods: The CLEAR SYNERGY trial is a 2 × 2 factorial randomized controlled trial of low-dose colchicine 0.5 mg daily versus placebo and spironolactone 25 mg daily versus placebo in 7,062 post-MI participants who were within 72 hours of the index percutaneous coronary intervention (PCI). We blinded participants, healthcare providers, research personnel, and outcome adjudicators to treatment allocation. The primary outcome for colchicine is the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The coprimary outcomes for spironolactone are (1) the composite of the total numbers of cardiovascular death or new or worsening heart failure and (2) the first occurrence of the composite of cardiovascular death, new or worsening heart failure, recurrent MI or stroke. We finished recruitment with 7,062 participants from 104 centers in 14 countries on November 8, 2022, and plan to present the results in the fall of 2024., Conclusions: CLEAR SYNERGY is a large international randomized controlled trial that will inform the effects of low-dose colchicine and spironolactone in largely unselected post-MI patients who undergo PCI. (ClinicalTrials.gov Identifier: NCT03048825)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear., Objectives: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI., Methods: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI., Results: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment., Conclusions: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment., Competing Interests: Funding Support and Author Disclosures This trial was led by the Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION) Study Group, an Academic Research Organization based at Pitié-Salpêtrière Hospital in Paris, France. It was sponsored by Assistance Publique-Hôpitaux de Paris and was funded by an unrestricted grant from AstraZeneca. AstraZeneca was not involved in the data collection, analysis, or in the writing of the manuscript. The Steering Committee oversaw the conduct of the trial in collaboration with representatives of the study sponsor. The trial was monitored by an independent Data and Safety Monitoring Board. Data were collected and analyzed according to the predefined statistical analysis plan by academic statisticians of the ACTION group. Drs Silvain and Montalescot had full access to the data and final responsibility for the decision to submit for publication. There was no medical writing support. Dr Manzo-Silberman has received consulting fees from Bayer, Organon, and Exeltis; has received lecture fees from Bayer, BMS, Exeltis Organon, and Terumo; and has served on the adjudication board for a study for Biotronik. Dr Beygui has received consulting and lecture fees from AstraZeneca, Bristol Myers Squibb, Medtronic, Biosensors, Boston Scientific; and has received institutional research grants from Medtronic, Biosensors, Acist, and Boston Scientific. Dr Cayla has received speaker or congress fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport CRM, Pfizer, and Sanofi; and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport CRM, Pfizer, and Sanofi. Dr Rangé has received speaker and/or consulting fees from Abbott, Biotronik, and Microport. Dr Motovska has received consulting, speaker, investigator and advisory board fees from AstraZeneca, Boehringer Ingelheim, and Idorsia. Dr Zeitouni has received research grants from Federation Française de Cardiologie and Institut Servier; and has received honoraria from BMS/Pfizer, Bayer, AstraZeneca, and Novo Nordisk. Dr Vicaut has received consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards Lifesciences, Pfizer, Sanofi, and Novartis. Dr Montalescot has received consulting or speaker fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, and Terumo. Dr Silvain has received consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, Sanofi Aventis France, Abbott Medical France, SAS, and Zoll; and is a stockholder of 4P-Pharma. 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.)

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent (Boston Scientific Corporation, Marlborough, Massachusetts) in patients with ST-elevation myocardial infarction (STEMI). The only drug-eluting stent approved for treatment of STEMI by the Food and Drug Administration is the Taxus stent (Boston Scientific) which is no longer commercially available, so further data are needed. The CLEAR (Colchicine and spironolactone in patients with myocardial infarction) SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (n = 7,000), comparing colchicine versus placebo and spironolactone versus placebo. The primary outcome for the SYNERGY stent registry is major adverse cardiac events (MACE) as defined by cardiovascular death, recurrent MI, or unplanned ischemia-driven target vessel revascularization within 12 months. We estimated a MACE rate of 6.3% at 12 months after primary percutaneous coronary intervention for STEMI based on the Thrombectomy vs percutaneous coronary intervention alone in STEMI (TOTAL) trial. Success was defined as upper bound of confidence interval (CI) to be less than the performance goal of 9.45%. Overall, 733 patients were enrolled from 8 countries with a mean age 60 years, 19.4% diabetes mellitus, 41.3% anterior MI, and median door-to-balloon time of 72 minutes. The MACE rate was 4.8% (95% CI 3.2 to 6.3%) at 12 months which met the success criteria against performance goal of 9.45%. The rates of cardiovascular death, recurrent MI, or target vessel revascularization were 2.7%, 1.9%, 1.0%, respectively. The rates of acute definite stent thrombosis were 0.3%, subacute 0.4%, late 0.4%, and cumulative stent thrombosis of 1.1% at 12 months. In conclusion, the SYNERGY stent in STEMI performed well and was successful compared with the performance goal based on previous trials., Competing Interests: Declaration of competing interest Dr. Jolly reports financial support was provided by Boston Scientific Corp. Dr. Jolly reports financial support was provided by Canadian Institutes of Health Research. Dr. Sabate reports consulting for Abbott Vascular and iVascular. Natalia Pinilla-Echeverri reports consulting for Conavi, Amgen, Bayer, and Novartis; financial support provided by Abbott Vascular; and an advisory board position at Philips. Dr. Mehta reports consulting for and financial support provided by Abbott, Amgen, Bristol-Myers Squibb, HLS Therapeutics, Janssen, Merck, Novartis, and Novo Nordisk. The remaining authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. 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.

Aims: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry., Methods and Results: In total, 1075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialized centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1 year. The mean age was 68 years and 260 (25%) were women. 13.5%, 30.9%, and 55.6% had one-vessel, two-vessel, and three-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0%. 54.2% of the patients had cardiac arrest before admission. Thrombolysis in myocardial infarction (TIMI) 3 patency of the infarct vessel after percutaneous coronary intervention was achieved in 83.6% of all patients. Mechanical circulatory support was applied in one-third of patients. Total mortality after 30 days and 1 year was 47.6% and 52.9%. Mortality after 1 year was highest in patients with LM coronary artery stenosis (63.5%), followed by three-vessel (56.6%), two-vessel (49.8%), and one-vessel CAD (38.6%), respectively. Mechanical complications were rare (21/1008; 2.1%) but associated with a high mortality of 66.7% after 1 year., Conclusion: In specialized centres in Europe, short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depends on the extent of CAD. Therefore, there is still a need for improvement of care to improve the prognosis of infarct-related CS., Competing Interests: Conflict of interest: None declared., (© 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: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice., Methods: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days., Results: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83])., Conclusions: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180., Competing Interests: Disclosures Dr Yan was funded by grants from the National Natural Science Foundation of China (82100260) and Beijing Hospitals Authority Youth Program (QML20210605). Dr X. Wang was funded by grants from National Key Research & Development Program of China (2022YFC2505600), Beijing Nova Program (Z201100006820087), Interdisciplinary Cooperation Project of Beijing Nova Program (Z211100002121165), and Natural Science Foundation of Beijing, China (7222046). Dr Ma reports honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, Bayer, and AstraZeneca for giving lectures. Dr Vicaut reports consulting fees from Abbott and Bristol-Myers Squibb. Dr Montalescot reports research grants to the institution or consulting or lecture 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. Dr Nie was funded by Beijing Hospitals Authority Clinical Medicine Development of Special Funding support (grant ZLRK202318), National Natural Science Foundation of China (grant 82270258), and Beijing Municipal Science & Technology Commission, China (grant Z221100003522027), and reports research grants to the institution from Boston Scientific, Abbott, Jiangsu Hengrui Pharmaceuticals, China Resources Sanjiu Medical & Pharmaceuticals, and East China Pharmaceuticals. The other authors have no conflicts of interest to declare.

Background: The effect of administering a crushed prasugrel loading dose is uncertain in patients presenting with a large myocardial infarction and ST-segment elevation myocardial infarction (STEMI)., Aims: The aim of this study was to investigate if patients with a large myocardial infarction may benefit from prehospital administration of a crushed prasugrel loading dose., Methods: Patients from the CompareCrush trial with an available ambulance electrocardiography (ECG) were included in the study. An independent core laboratory confirmed a prehospital large myocardial area. We compared pre- and postprocedural angiographic markers, including Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, high thrombus burden, and myocardial blush grade 3, in STEMI patients with and without a prehospital large myocardial area., Results: Ambulance ECG was available for 532 patients, of whom 331 patients were identified with a prehospital large myocardial area at risk. Crushed prasugrel significantly improved postprocedural TIMI 3 flow rates in STEMI patients with a prehospital large myocardial area at risk (92% vs 79%, odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.50-6.00) but not in STEMI patients without a prehospital large myocardial area at risk (91% vs 95%, OR 0.47, 95% CI: 0.14-1.57; p interaction =0.009)., Conclusions: Administration of crushed prasugrel may improve postprocedural TIMI 3 flow in STEMI patients with signs of a large myocardial area at risk on the ambulance ECG. The practice of crushing tablets of prasugrel loading dose might, therefore, represent a safe, fast and cost-effective strategy to improve myocardial reperfusion in this high-risk STEMI subgroup undergoing primary percutaneous coronary intervention.

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: 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.)

Background: Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI., Study Design: APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power., Conclusion: The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone., Clinicaltrials: gov Identifier: NCT05077683., Competing Interests: Disclosures EP has received fees for lectures and/or consulting: Amgen, Astra-Zeneca, BMS, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, MSD, Novartis, Pfizer, The Medicine Company, Sanofi, Saint Jude Medical, Servier, Siemens. BAYER is a sponsor of the trial., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI., Methods: The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups., Results: Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04)., Conclusions: In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Early and complete restoration of target vessel patency in ST-elevation myocardial infarction (STEMI) is associated with improved outcomes. Oral P2Y 12 inhibitors have failed to demonstrate either improved patency or reduced mortality when administered in the prehospital setting. Thus, there is a need for antiplatelet agents that achieve prompt and potent platelet inhibition, and that restore patency in the prehospital setting. Zalunfiban, a novel subcutaneously administered glycoprotein IIb/IIIa inhibitor designed for prehospital administration, has shown to achieve rapid, high-grade platelet inhibition that exceeds that of P2Y 12 inhibitors. Whether prehospital administration of zalunfiban can improve clinical outcome is unknown., Hypothesis: The present study is designed to assess the hypothesis that a single, prehospital injection of zalunfiban given in the ambulance, in addition to standard-of-care in patients with STEMI with intent to undergo primary percutaneous coronary intervention (PCI) will improve clinical outcome compared to standard-of-care with placebo., Study Design: The ongoing CELEBRATE trial (NCT04825743) is a phase 3, randomized, double-blinded, placebo-controlled, international trial. Patients with STEMI intended to undergo primary PCI will receive treatment with a single subcutaneous injection containing either zalunfiban dose 1 (0.110 mg/kg), zalunfiban dose 2 (0.130 mg/kg) or placebo, and the study drug will be administered in the ambulance before transportation to the hospital. A target of 2499 patients will be randomly assigned to one of the treatment groups in a 1:1:1 ratio, ie, to have approximately 833 evaluable patients per group. The primary efficacy outcome is a ranked 7-point scale on clinical outcomes. The primary safety outcome is severe or life-threatening bleeding according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria., Summary: The CELEBRATE trial will assess whether a single prehospital subcutaneous injection of zalunfiban in addition to standard-of-care in patients with STEMI with intent to undergo primary PCI will result in improved clinical outcome., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS)., Objectives: The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry., Methods: Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed., Results: Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6)., Conclusions: More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549)., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant agreement (602202) from the European Union Seventh Framework Program and by the German Heart Research Foundation and the German Cardiac Society. It was also supported by the German Center for Cardiovascular Research (DZHK). Dr Zeymer has received grants from the European Union within the study; has received grants and personal fees from AstraZeneca, Bayer, BMS, Daiichi-Sankyo, and Novartis; and has received personal fees from Boehringer Ingelheim, The Medicines Company, Sanofi, and Ferrer, outside the submitted work. Dr Montalescot has received research grants to the institution or consulting/lecture fees from Abbott, Amgen, Actelion, American College of Cardiology Foundation, AstraZeneca, Axis-Santé, Bayer, Boston Scientific, Boehringer Ingelheim, Bristol Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, China Heart House, Daiichi-Sankyo, Idorsia, Elsevier, Europa, Fédération Française de Cardiologie, ICAN, Lead-Up, Medtronic, Menarini, MSD, Novo Nordisk, Partners, Pfizer, Quantum Genomics, Sanofi, Servier, and WebMD. Dr Desch has received grants from the European Union during the conduct of the study. Dr Thiele has received grants to the institution from the European Union, German Cardiac Society, and German Heart Research Foundation during the conduct of the study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In-hospital cardiac arrest (IHCA) is one of the most deleterious complications of ST-segment elevation myocardial infarction (STEMI)., Objectives: We systematically analyzed the clinical characteristics of STEMI patients with IHCA, as well as predictors and treatments associated with risk of IHCA, using a nationwide database., Methods: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we stratified patients presenting with STEMI within 24 hours after symptom onset according to IHCA or no IHCA during the index hospitalization. We analyzed patients' clinical characteristics, mortality, and independent correlates of IHCA., Results: Of 40,670 STEMI patients, 2.2% (95% CI: 2.1%-2.4%) experienced IHCA. Among IHCA patients, the in-hospital mortality was 53.0% (95% CI: 49.7%-56.3%). IHCA represents 55.0% (95% CI: 51.6%-58.4%) of inpatient deaths. Age ≥75 years, female, nonsmoker, prior diabetes mellitus, prior renal failure, out-of-hospital cardiac arrest, heart rate >100 beats/min, systolic blood pressure <90 mm Hg, and Killip IV were identified as predictors of IHCA. IHCA patients were less likely to receive β-blockers and ticagrelor during the first 24 hours after first medical contact and were less likely to undergo primary percutaneous coronary intervention. After adjustment, primary percutaneous coronary intervention (adjusted HR: 0.82; 95% CI: 0.71-0.95), β-blockers (adjusted HR: 0.63; 95% CI: 0.47-0.86), and ticagrelor (adjusted HR: 0.57; 95% CI: 0.42-0.76) were associated with a reduced risk of IHCA., Conclusions: IHCA is rare in STEMI but is associated with high mortality. Multiple modifiable and unmodifiable factors are associated with its occurrence, suggesting that early intervention and rational drug treatment may improve its prognosis. (CCC Project- Acute Coronary Syndrome; NCT02306616)., Competing Interests: Funding Support and Author Disclosures The CCC-ACS project is a collaborative study of the American Heart Association and the Chinese Society of Cardiology. The American Heart Association has been funded by Pfizer and AstraZeneca for quality improvement initiatives through an independent grant. Dr Gong was funded by grants from the National Natural Science Foundation of China (81970292, 81600213), Beijing Hospitals Authority Youth Program (QML20190603), and CS Optimizing Antithrombotic Research Fund (BJUHFCSOARF201901-08). Dr Yan was supported by grants from the National Natural Science Foundation of China (82100260) and Beijing Hospitals Authority Youth Program (QML20210605). Dr Ma has received honoraria from Bristol Myers Squibb, Pfizer, Johnson and Johnson, Boehringer Ingelheim, Bayer, and AstraZeneca for giving lectures. Dr Montalescot has received research grants to the institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell-Prothera, Europa, IRIS-Servier, Novartis, Medtronic, Merck Sharp & Dohme, Pfizer, Quantum Genomics, and Sanofi. Dr Nie was funded by Natural Science Foundation of Beijing, China (7191002), National Key Research and Development Program of China (2020YFC2004800), National Natural Science Foundation of China (81670222), the Capital Health Research and Development of Special Fund (2018-1-2061), and Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20180601); and has received research grants to the institution from Boston Scientific, Abbott, Jiangsu Hengrui, China Resources Sanjiu, and Huadong Medicine. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with ST-segment elevation myocardial infarction (STEMI) who have multivessel disease, the FLOWER-MI trial found no significant clinical benefit to fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared to angiography-guided PCI., Aims: Our aim was to estimate the cost-effectiveness and cost-utility of FFR-guided PCI, the secondary endpoint of the FLOWER-MI trial., Methods: Costs, major adverse cardiovascular events (composite of all-cause death, non-fatal myocardial infarction [MI], and unplanned hospitalisation leading to urgent revascularisation), and quality-adjusted life years were calculated in both groups. The incremental cost-effectiveness and cost-utility ratios were estimated. Uncertainty was explored by probabilistic bootstrapping. The analysis was conducted from the perspective of the health care provider with a time horizon of one year., Results: At one year, the average cost per patient was 7,560€ (±2,218) in the FFR-guided group and 7,089€ (±1,991) in the angiography-guided group (p-value<0.01). The point estimates for the incremental cost-effectiveness and cost-utility ratios found that the angiography-guided strategy was cost saving and improved outcomes, with a probabilistic sensitivity analysis confirming dominance., Conclusions: The FFR-guided strategy at one year is unlikely to be cost effective compared to the angiography-guided strategy on both clinical and quality of life outcomes.

Objectives: This study sought to assess the association between postprocedural anticoagulation (PPAC) use and several clinical outcomes., Background: PPAC after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI) may prevent recurrent ischemic events but may increase the risk of bleeding. No consensus has been reached on PPAC use., Methods: Using data from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome registry, conducted between 2014 and 2019, we stratified all STEMI patients who underwent pPCI according to the use of PPAC or not. Inverse probability of treatment weighting and a Cox proportional hazards model with hospital as random effect were used to analyze differences in in-hospital clinical outcomes: the primary efficacy endpoint was mortality and the primary safety endpoint was major bleeding., Results: Of 34,826 evaluable patients, 26,272 (75.4%) were treated with PPAC and were on average younger, more stable at admission with lower bleeding risk score, more likely to have comorbidities and multivessel disease, and more often treated within 12 hours of symptom onset than those without PPAC. After inverse probability of treatment weighting adjustment for baseline differences, PPAC was associated with significantly reduced risk of in-hospital mortality (0.9% vs 1.8%; HR: 0.62; 95% CI: 0.43-0.89; P < 0.001) and a nonsignificant difference in risk of in-hospital major bleeding (2.5% vs 2.2%; HR: 1.05; 95% CI: 0.83-1.32; P = 0.14)., Conclusions: PPAC in STEMI patients after pPCI was associated with reduced mortality without increasing major bleeding complications. Dedicated randomized trials with contemporary STEMI management are needed to confirm these findings., Competing Interests: Funding Support and Author Disclosures The Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome project is a collaborative study of the American Heart Association and the Chinese Society of Cardiology. The American Heart Association has been funded by Pfizer and AstraZeneca for quality improvement initiatives through an independent grant. Dr Yan was funded by grants from the National Natural Science Foundation of China (No. 82100260), the Fund for Beijing Science and Technology Development of TCM (No. QN2018-01), and the Beijing Municipal Administration of Hospitals Incubating Program (No. PZ2019005). Dr Gong was funded by grants from the National Natural Science Foundation of China (Nos. 81970292 and 81600213), Beijing Hospitals Authority Youth Program (No. QML20190603), and CS Optimizing Antithrombotic Research Fund (No. BJUHFCSOARF201901-08). Dr Wang was funded by Beijing Nova Program (No. Z201100006820087). Dr Ma has received lecture honoraria from Bristol Myers Squibb, Pfizer, Johnson and Johnson, Boehringer Ingelheim, Bayer, and AstraZeneca. Dr Montalescot has received institutional research grants or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CellProthera, Europa, IRIS-Servier, Novartis, Medtronic, Merck Sharp & Dohme, Pfizer, Quantum Genomics, and Sanofi. Dr Nie has received institutional research grants from Boston Scientific, Abbott, Jiangsu Hengrui, China Resources Sanjiu, and Huadong Medicine. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with ST-segment-elevation myocardial infarction and multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions guided by fractional flow reserve (FFR) is superior to treatment of the culprit lesion alone. Whether deferring nonculprit PCI is safe in this specific context is questionable. We aimed to assess clinical outcomes at 1 year in ST-segment-elevation myocardial infarction patients with multivessel coronary artery disease and an FFR-guided strategy for nonculprit lesions, according to whether or not ≥1 PCI was performed., Methods: Outcomes were analyzed in patients of the randomized FLOWER-MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) trial in whom, after successful primary PCI, nonculprit lesions were assessed using FFR. The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization with urgent revascularization at 1 year., Results: Among 1171 patients enrolled in this study, 586 were assigned to the FFR-guided group: 388 (66%) of them had ≥1 PCI, and 198 (34%) had no PCI. Mean FFR before decision (ie, PCI or not) of nonculprit lesions was 0.75±0.10 and 0.88±0.06, respectively. During follow-up, a primary outcome event occurred in 16 of 388 patients (4.1%) in patients with PCI and in 16 of 198 patients (8.1%) in patients without PCI (adjusted hazard ratio, 0.42 [95% CI, 0.20-0.88]; P =0.02)., Conclusions: In patients with ST-segment-elevation myocardial infarction undergoing complete revascularization guided by FFR measurement, those with ≥1 PCI had lower event rates at 1 year, compared with patients with deferred PCI, suggesting that deferring lesions judged relevant by visual estimation but with FFR >0.80 may not be optimal in this context. Future randomized studies are needed to confirm these data. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954. Graphic Abstract: A graphic abstract is available for this article.

Background Little is known about the impact of center volume on outcomes in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to investigate the association between center volume, treatment strategies, and subsequent outcome in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results In this subanalysis of the randomized CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, study sites were categorized based on the annual volume of acute myocardial infarction complicated by cardiogenic shock into low-/intermediate-/high-volume centers (<50; 50-100; and >100 cases/y). Subjects from the study/compulsory registry with available volume data were included. Baseline/procedural characteristics, overall treatment, and 1-year all-cause mortality were compared across categories. n=1032 patients were included in this study (537 treated at low-volume, 240 at intermediate-volume, and 255 at high-volume centers). Baseline risk profile of patients across the volume categories was similar, although high-volume centers included a larger number of older patients. Low-/intermediate-volume centers had more resuscitated patients (57.5%/58.8% versus 42.2%; P <0.01), and more patients on mechanical ventilation in comparison to high-volume centers. There were no differences in reperfusion success despite considerable differences in adjunctive pharmacological/device therapies. There was no difference in 1-year all-cause mortality across volume categories (51.1% versus 56.5% versus 54.4%; P =0.34). Conclusions In this study of patients with acute myocardial infarction complicated by cardiogenic shock, considerable differences in adjunctive medical and mechanical support therapies were observed. However, we could not detect an impact of center volume on reperfusion success or mortality.

Background: Critical culprit lesion locations (CCLL) such as left main (LM) and proximal left anterior descending (LAD) are associated with worse clinical outcome in myocardial infarction without cardiogenic shock (CS)., Aims: We aimed to assess whether CCLL identify a subgroup of patients with poorer prognosis when presenting with CS., Methods: In the CULPRIT-SHOCK trial, a core laboratory reviewed all coronary angiograms to identify CCLL. A CCLL was defined as a culprit lesion with a >70% diameter stenosis of the LM, LM equivalent (>70% diameter stenosis of both proximal LAD and proximal circumflex), proximal LAD or last remaining vessel. We evaluated the primary study endpoint of the CULPRIT-SHOCK trial according to CCLL., Results: A total of 269 (43%) out of 626 patients eligible for this analysis had a CCLL. Death or renal replacement therapy within 30 days, death within 30 days and death within one year were significantly higher in the CCLL than in the non-CCLL group (58.4% vs 43.4%, p<0.001, 55.8% vs 39.5%, p<0.001, 61.0% vs 44.5%, p<0.001, respectively). This was consistent after adjustment for baseline and angiographic characteristics. No interaction with the randomisation group (culprit lesion-only or immediate multivessel PCI) was found., Conclusions: CCLL is frequent in CS and independently associated with worse clinical outcomes irrespective of the revascularisation strategy., Trial Registration: www.clinicaltrials.gov NCT01927549.

Background: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear., Methods: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year., Results: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively., Conclusions: In patients with STEMI 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 at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.)., (Copyright © 2021 Massachusetts Medical Society.)

Objectives: This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y 12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI)., Background: Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y 12 inhibitor effect is delayed and varies according to formulation administered., Methods: The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion., Results: A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y 12 reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40)., Conclusions: Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition., Competing Interests: Funding Support and Author Disclosures The COMPARE CRUSH trial was funded by Maasstad Research B.V. (Rotterdam, the Netherlands), which received unrestricted grants from Daiichi-Sankyo and Shanghai MicroPort Medical. The funding companies were not involved in the conduct of the trial, the analysis of the data, or the drafts of the manuscripts. Dr. Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St. Jude Medical; and has received institutional research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr. Alexopoulos has received consulting fees or honoraria from AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Chiesi Hellas, Medtronic, and Pfizer. Dr. Montalescot has received research or institutional grant support or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CellProthera, Europa, IRIS-Servier, Novartis, Medtronic, MSD, Pfizer, Quantum Genomics, and Sanofi. Dr. Van Mieghem has received institutional research grant support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, Teleflex, PulseCath BV, and Daiichi-Sankyo. Dr. Smits has received research grant support from Daiichi-Sankyo and Shanghai MicroPort. Dr. Vlachojannis has received consulting fees from AstraZeneca; and research grant support from Daiichi-Sankyo and Shanghai MicroPort. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: ST-elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) are associated with a worse prognosis. However, few comparisons are available according to coronary status in the era of modern reperfusion and optimized secondary prevention., Hypothesis: We hypothesized that the difference in prognosis according to number of vessel disease in STEMI patients has reduced., Methods: All consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) within 24 h of symptoms onset between January 1, 2014 and June 30, 2016 enrolled in the CRAC (Club Régional des Angioplasticiens de la région Centre) France PCI registry were analyzed. Baseline characteristics, management, and outcomes at 1-year were analyzed according to coronary status (one-, two-, and three-VD)., Results: A total of 1886 patients (mean age 62.2 ± 14.0 year; 74% of male) were included. Patients with MVD (two or three-VD) represented 53.7%. They were older with higher cardiovascular risk factor profile. At 1 year, the rate of major adverse cardiovascular events (MACE, defined as all-cause death, stroke or re-MI) was 10%, 12%, and 12% in one-, two, and three-VD respectively (p = .28). In multivariable adjusted Cox proportional hazard regression model, two- and three-VD were not associated with higher rate of MACE compared to patients with single VD (HR, 1.09; 95%CI 0.76-1.56 for two-VD; HR, 0.74; 95%CI 0.48-1.14 for three-VD)., Conclusions: MVD still represents an important proportion of STEMI patients but their prognoses were not associated with worse clinical outcomes at 1-year compared with one-VD patients in a modern reperfusion area and secondary medication prevention., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Aims: The aim of this study was to determine the prognostic impact of pre- and post-PCI TIMI flow grade and TIMI myocardial perfusion grade (TMPG) in a well-defined group of patients with cardiogenic shock due to acute myocardial infarction., Methods and Results: Patients with infarct-related cardiogenic shock randomised into the CULPRIT-SHOCK trial were included in the angiographic predictor analysis whenever their TIMI flow grade or TMPG was available in the core lab database (96.9% of cases). A multivariable logistic regression analysis, adjusted on non-angiographic covariates, was performed to investigate whether TIMI flow grade or TMPG was independently associated with all-cause mortality or renal replacement therapy up to one year. Pre-PCI TIMI flow grade and TMPG did not impact on mortality. When analysed in separate multivariable models, post-PCI TIMI 3 flow and TMPG grade 3 were both significantly associated with reduced risk of 30-day mortality: aOR 0.61 (95% CI: 0.38-0.97, p=0.037) and 0.46 (95% CI: 0.29-0.72, p<0.001), respectively. When considered in the same multivariable model, only TMPG was significantly associated with 30-day mortality (aOR 0.38 [0.20-0.71], p=0.002), the 30-day composite of all-cause mortality and renal replacement therapy (aOR 0.34 [0.18-0.66], p=0.001) and mortality at one-year follow-up (aOR 0.46 [0.24-0.88], p=0.02)., Conclusions: Post-PCI TIMI flow grade and TMPG are associated with mortality after PCI. TMPG is a better discriminator, supporting microcirculation rather than epicardial reperfusion for prognosis estimation.

Background: Despite the overall neutral results of the GLOBAL-LEADERS trial, results from a prespecified subgroup analysis showed that patients from Western Europe had a significantly lower rate of the primary endpoint when treated with ticagrelor monotherapy. Therefore, we aimed to examine the regional disparities in patients' baseline characteristics and their response to ticagrelor monotherapy., Methods: Patients' baseline characteristics and the treatment effects of ticagrelor combined with aspirin for 1 month, followed by ticagrelor monotherapy for 23-months versus 12-months of standard dual antiplatelet therapy (DAPT) were compared according to participating countries. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at two years., Results: Significant variances in patients' baseline characteristics were found between participating countries. The primary endpoint varied significantly according to the country (P interaction  = 0.027). Patients from France (1.6% versus 5.2%, HR: 0.31, 95%CI: 0.13-0.73) and The Netherlands (2.4% versus 4.8%, HR, 0.50, 95%CI: 0.26-0.94) had lower rates of the primary endpoint when allocated to ticagrelor monotherapy, compared with the standard DAPT regimen. Of the 26 baseline and post-randomization factors explored, variance in the rate of complex PCI between countries was identified as the top contributor to this regional interaction., Conclusions: Patients' baseline characteristics varied between participating countries in the GLOBAL-LEADERS trial. There is a significant regional variance in the treatment effect of ticagrelor monotherapy, which could partly be explained by the differences in complex PCI being performed., Clinical Trial Registration: ClinicalTrials.gov (NCT01813435)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The impact of coronary artery chronic total occlusion (CTO) and its management with percutaneous coronary intervention (PCI) in the setting of myocardial infarction (MI) related cardiogenic shock (CS) remains unclear., Methods: This is a pre-specified analysis from the culprit-lesion-only PCI vs multivessel PCI in CS (CULPRIT-SHOCK) trial which randomized patients presenting with MI and multivessel disease complicated by CS to a culprit-lesion-only or immediate multivessel PCI strategy. CTO was defined by central core-laboratory evaluation. The independent associations between the presence of CTO and adverse outcomes at 30 days and 1 year were assessed using multivariate logistics models., Results: A noninfarct related CTO was present in 157 of 667 (23.5%) analyzed patients. Patients presenting with CTO had more frequent diabetes mellitus or prior PCI but less frequently presented with ST segment elevation MI as index event. The presence of CTO was associated with higher rate of death at 30 days (adjusted Odds ratio 1.63; 95% confidence interval [CI] 1.01-2.60). Rate of death at 1 year was also increased but did not reach statistical significance (adjusted Odds ratio 1.62; 95%CI 0.99-2.66). Compare to immediate multivessel PCI, a strategy of culprit-lesion-only PCI was associated with lower rates of death or renal replacement therapy at 30 days in patients with and without CTO (Odds ratio 0.79 95%CI 0.42-1.49 and Odds ratio 0.67 95%CI 0.48-0.96, respectively), without significant interaction (P = .68)., Conclusions: In patients with MI-related CS and multivessel disease, the presence of CTO is associated with adverse outcomes while a strategy of culprit-lesion-only PCI seems beneficial regardless of the presence of CTO., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated., Methods and Results: We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84-1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32-3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42-7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin)., Conclusion: Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect 'major' procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: In hemodynamically stable patients, complete revascularization (CR) following percutaneous coronary intervention (PCI) is associated with a better prognosis in chronic and acute coronary syndromes., Objectives: This study sought to assess the extent, severity, and prognostic value of remaining coronary stenoses following PCI, by using the residual SYNTAX score (rSS), in patients with cardiogenic shock (CS) related to myocardial infarction (MI)., Methods: The CULPRIT-SHOCK (Culprit Lesion Only Percutaneous Coronary Intervention [PCI] Versus Multivessel PCI in Cardiogenic Shock) trial compared a multivessel PCI (MV-PCI) strategy with a culprit lesion-only PCI (CLO-PCI) strategy in patients with multivessel coronary artery disease who presented with MI-related CS. The rSS was assessed by a central core laboratory. The study group was divided in 4 subgroups according to tertiles of rSS of the participants, thereby isolating patients with an rSS of 0 (CR). The predictive value of rSS for the 30-day primary endpoint (mortality or severe renal failure) and for 30-day and 1-year mortality was assessed using multivariate logistic regression., Results: Among the 587 patients with an rSS available, the median rSS was 9.0 (interquartile range: 3.0 to 17.0); 102 (17.4%), 100 (17.0%), 196 (33.4%), and 189 (32.2%) patients had rSS = 0, 0 < rSS ≤5, 5 < rSS ≤14, and rSS >14, respectively. CR was achieved in 75 (25.2%; 95% confidence interval [CI]: 20.3% to 30.5%) and 27 (9.3%; 95% CI: 6.2% to 13.3%) of patients treated using the MV-PCI and CLO-PCI strategies, respectively. After multiple adjustments, rSS was independently associated with 30-day mortality (adjusted odds ratio per 10 units: 1.49; 95% CI: 1.11 to 2.01) and 1-year mortality (adjusted odds ratio per 10 units: 1.52; 95% CI: 1.11 to 2.07)., Conclusions: Among patients with multivessel disease and MI-related CS, CR is achieved only in one-fourth of the patients treated using an MV-PCI strategy. and the residual SYNTAX score is independently associated with early and late mortality., Competing Interests: Author Disclosures The CULPRIT-SHOCK trial was supported by a grant agreement (602202) from the European Union Seventh Framework Program and by the German Heart Research Foundation and the German Cardiac Society. The current substudy was led by the ACTION Study Group at the Institut de Cardiologie, Hôpital de Pitié-Salpêtrière, Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France. Dr. Zeitouni has received research grants from Institut Servier, Bristol Myers Squibb/Pfizer, and Federation Française de Cardiologie. Dr. Vicaut has received personal fees from Eli Lilly; has been a consultant for Pfizer, Sanofi, LFB, Abbott, Fresenius, Medtronic, and Hexacath; is a member of the data safety monitoring board for CERC; has received lecture fees from Novartis; and has received grants from Boehringer Ingelheim and Sanofi. Dr. Zeymer has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Sanofi, Merck Sharp and Dohme, The Medicines Company, Pfizer, Daiichi-Sankyo, Eli Lilly, and Abiomed, outside the submitted work. Dr. Montalescot has received institutional research grants or consulting or lecture fees from Abbott, AIM group, Amgen, Actelion, American College of Cardiology Foundation, AstraZeneca, Axis-Santé, Bayer, Boston Scientific, Bristol Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Fréquence Médicale, ICOM, Idorsia, Elsevier, Fédération Française de Cardiologie, Fréquence Médicale, ICAN, Lead-Up, Menarini, Medtronic, Merck Sharp and Dohme, Novo-Nordisk, Pfizer, Quantum Genomics, Sanofi-Aventis, SCOR Global Life, Servier, and WebMD. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Early treatment with a potent oral platelet P2Y 12 inhibitor is recommended in patients presenting with ST-segment-elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y 12 inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown., Methods: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment-elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes., Results: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47-70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65-1.30], P =0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78-1.58], P =0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y 12 reactivity unit, differed significantly between groups (crushed, 192 [132-245] versus integral, 227 [184-254], P ≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days., Conclusions: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment-elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296540.

Importance: Myocardial infarction with a culprit lesion located in the left main or proximal left anterior descending artery compared with other coronary segments is associated with more myocardium at risk and worse clinical outcomes., Objective: To evaluate the association of culprit lesion location with outcomes of culprit-lesion-only percutaneous coronary intervention with optional staged revascularization vs immediate multivessel percutaneous coronary intervention in patients with multivessel disease, myocardial infarction, and cardiogenic shock., Design, Setting, and Participants: Post hoc analysis of the Culprit Lesion Only Coronary Intervention vs Multivessel Coronary Intervention in Cardiogenic Shock (CULPRIT-SHOCK), an investigator-initiated randomized, open-label clinical trial. Patients with multivessel disease, acute myocardial infarction, and cardiogenic shock were enrolled at 83 European centers from April 2013 through April 2017., Interventions: Patients were randomized to culprit-lesion-only percutaneous coronary intervention with optional staged revascularization or immediate multivessel percutaneous coronary intervention (1:1). For this analysis, patients were stratified by culprit lesion location in the left main or proximal left anterior descending artery group and other-culprit-lesion location group., Main Outcomes and Measures: End points included a composite of death or kidney replacement therapy at 30 days and death at 1 year., Results: The median age of the study population was 70 (interquartile range, 60-78 years) and 524 of the study participants were men (76.4%). Of the 685 patients, 33.4% constituted the left main or proximal left anterior descending artery group and 66.6% the other-culprit-lesion location group. The left main or proximal left anterior descending artery group had worse outcomes compared with the other-culprit-lesion location group (56.8% vs 47.5%; P = .02 for the composite end point at 30 days and 59.8% vs 50.1%; P = .02 for death at 1 year). In both groups, culprit-lesion-only vs immediate multivessel percutaneous coronary intervention was associated with a reduced risk of the composite end point at 30 days (49.1% vs 64.3% and 44.1% vs 50.9%; P for interaction = .27). At 1 year, culprit-lesion-only vs immediate multivessel percutaneous coronary intervention was associated with a significantly reduced risk of death in the left main or proximal left anterior descending artery but not the other-culprit-lesion location group (50.0% vs 69.6%; P = .003 and 49.8% vs 50.4%; P = .89; P for interaction = 0.02)., Conclusions and Relevance: In patients with multivessel disease with myocardial infarction and cardiogenic shock, a culprit lesion located in the left main or proximal left anterior descending artery vs other coronary segments was associated with worse outcomes. These patients may especially benefit from culprit-lesion-only percutaneous coronary intervention with optional staged revascularization, although further investigation is needed to confirm this finding., Trial Registration: ClinicalTrials.gov Identifier: NCT01927549.

Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI., Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290., Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070)., Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI., Funding: ACTION Study Group and AstraZeneca., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients., Methods: In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events., Results: At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66-2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p = 0.043, p interaction  = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56-0.99], p = 0.044, p interaction  = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29-0.82], p = 0.007, p interaction  = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29-0.82], p = 0.007, p interaction  = 0.013) in the second year., Conclusion: Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating., Clinical Trial Registration: ClinicalTrials.gov (NCT01813435).

Background: Current guidelines recommend anticoagulation therapy during primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). However, whether anticoagulation should be continued after pPCI has not been well investigated., Methods/design: The RIGHT trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in STEMI patients treated with pPCI evaluating the prolongation of anticoagulation after the procedure. Patients are randomized in a 1:1 fashion to receive either prolonged anticoagulant or matching placebo (no anticoagulation) for at least 48 hours after the procedure. When randomized to anticoagulation prolongation, the patient is assigned to intravenous unfractionated heparin (UFH) or subcutaneous enoxaparin or intravenous bivalirudin (same drug and same regimen at each center). The primary efficacy endpoint is the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) at 30 days. The primary safety endpoint is major bleeding (BARC 3-5) at 30 days. Based on a superiority design and assuming a 35% relative risk reduction (from 7% to 4.5%), 2856 patients will be enrolled, accounting for a 5% drop-out rate (α = 0.05 and power = 80%)., Conclusion: The RIGHT trial tests the hypothesis that post-procedural anticoagulation is superior to no anticoagulation in reducing ischemic events in STEMI patients undergoing pPCI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The management of patients with acute myocardial infarction complicated by cardiogenic shock is highly complex, and outcomes may depend on the time of hospital admission and subsequent intervention (ie, ON-hours versus OFF-hours). The CULPRIT-SHOCK trial (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) demonstrated superior outcome for culprit-lesion-only versus immediate multivessel percutaneous coronary intervention in patients presenting with acute myocardial infarction, multivessel disease, and cardiogenic shock. However, it is unknown whether the time of hospital admission affects the overall outcome of these high-risk patients., Methods: We analyzed patients from the CULPRIT-SHOCK trial with respect to the time of hospital admission. We divided patients in ON-hours and OFF-hours groups and further stratified them according to their individual revascularization strategy. Outcome measures consisted of a composite end point of death or renal-replacement therapy within 30 days and mortality within 1 year., Results: Out of 686 patients randomized in the CULPRIT-SHOCK trial, 444 patients (64.7%) presented during ON-hours, whereas 242 patients (35.3%) presented during OFF-hours. Death or renal-replacement therapy at 30 days occurred to a similar extent in patients admitted during ON-hours (51.0%) and OFF-hours (50.0%; P =0.80). Similarly, 1-year mortality was not affected by the time of hospital admission (54.4% ON-hours versus 51.7% OFF-hours, P =0.49). Regardless of admission time, patients had a benefit from culprit-lesion-only as compared to immediate multivessel percutaneous coronary intervention. The composite end point at 30 days occurred in 45.1% versus 57.6% of patients admitted ON-hours and in 47.7% versus 51.9% of patients admitted OFF-hours ( P interaction =0.29). Death within 1 year occurred in 49.4% versus 60.0% of patients admitted during ON-hours and in 51.4% versus 51.9% of patients admitted OFF-hours ( P interaction =0.20)., Conclusions: Among patients with myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days, and mortality at 1 year did not differ significantly according to the time of hospital admission. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01927549.

Background: The use and impact of transradial artery access (TRA) compared to transfemoral artery access (TFA) in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated by cardiogenic shock (CS) remain unclear., Methods: This is a post hoc analysis of the CULPRIT-SHOCK trial where patients presenting with MI and multivessel disease complicated by CS were randomized to a strategy of culprit-lesion-only or immediate multivessel PCI. Arterial access was left at operator's discretion. Adjudicated outcomes of interest were the composite of death or renal replacement therapy (RRT) at 30 days and 1 year. Multivariate logistic models were used to assess the association between the arterial access and outcomes., Results: Among the 673 analyzed patients, TRA and TFA were successfully performed in 118 (17.5%) and 555 (82.5%) patients, respectively. Compared to TFA, TRA was associated with a lower 30-day rate of death or RRT (37.3% vs 53.2%, adjusted odds ratio [aOR]: 0.57; 95% confidence interval [CI] 0.34-0.96), a lower 30-day rate of death (34.7% vs 49.7%; aOR: 0.56; 95% CI 0.33-0.96), and a lower 30-day rate of RRT (5.9% vs 15.9%; aOR: 0.40; 95% CI 0.16-0.97). No significant differences were observed regarding the 30-day risks of type 3 or 5 Bleeding Academic Research Consortium bleeding and stroke. The observed reduction of death or RRT and death with TRA was no longer significant at 1 year (44.9% vs 57.8%; aOR: 0.85; 95% CI 0.50-1.45 and 42.4% vs 55.5%, aOR: 0.78; 95% CI 0.46-1.32, respectively)., Conclusions: In patients undergoing PCI for acute MI complicated by CS, TRA may be associated with improved early outcomes, although the reason for this finding needs further research., Competing Interests: Disclosures Dr Zeymer reports personal fees from Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Novartis, Sanofi, MSD, The Medicines Company, Pfizer, Daiichi Sankyo, Eli Lilly, and Abiomed outside the submitted work. Dr Montalescot reports the following disclosures during the past 2 years: research grants to the institution or consulting/lecture fees from ADIR, Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, Celladon, CME Resources, Daiichi-Sankyo, Eli-Lilly, Europa, Elsevier, Fédération Française de Cardiologie, Fondazione Anna Maria Sechi per il Cuore, Gilead, ICAN, Janssen, Lead-Up, Menarini, Medtronic, MSD, Pfizer, Sanofi-Aventis, The Medicines Company, TIMI Study Group, and WebMD. Dr Windecker has received research, educational, and training grants from Amgen, Abbott, Bayer, Bristol-Myers Squibb, Boston Scientific, Biotronik, Medtronic, Edwards Lifesciences, St. Jude, and Terumo. Dr Silvain reports consulting fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, CSL Berhing, Gilead Science, and Sanofi Aventis; speaker honoraria from AstraZeneca, Amgen, Bayer, Algorythm, and Sanofi-Aventis; and travel support from Amgen, Astra-Zeneca, Bayer, and Bristol-Myer Squibb. Dr Kerneis has received research grants from Sanofi, Institut Servier, and Fédération Française de Cardiologie and consultant fees from Bayer and AstraZeneca. Dr Lattuca has received research grants from Biotronik, Daiichi-Sankyo, and Fédération Française de Cardiologie; consultant fees from Daiichi-Sankyo and Eli Lilly; and lecture fees from AstraZeneca and Novartis. Dr Michel Zeitouni has received research grants from Federation Française de Cardiologie and Institut Servier. Dr Collet has received research grants or honorarium from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli-Lilly, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD. All other authors do not report any disclosure relative to this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF., Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2 )., Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, p adj  = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, p int  = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, p int  = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int  = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int  = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF., Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy., Clinical Trial Registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435.

Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y 12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting., Methods: Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier)., Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y 12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown., Hypothesis: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose., Study Design: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours., Conclusions: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine frequency, associated factors, and impact of bleeding in infarct-related cardiogenic shock., Background: Early revascularization is associated with improved survival in patients with acute myocardial infarction complicated by cardiogenic shock. On the downside, invasive treatment and accompanying antithrombotic therapies are associated with an increased bleeding risk. Prospective data assessing the incidence, severity, risk factors, and prognostic implication of bleeding in patients with cardiogenic shock are scarce., Methods: As a pre-defined subanalysis of the CULPRIT-SHOCK (PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock) randomized trial, we examined distribution of bleeding events in 684 patients with infarct-related cardiogenic shock and compared patients with any bleeding to those without., Results: A total of 21.5% patients experienced at least 1 bleeding event until 30 days after randomization. The vast majority of bleeding (57%) occurred within the first 2 days of hospitalization. Patients with bleeding had prolonged catecholamine treatment and mechanical ventilation and there was a significant association with sepsis, peripheral ischemic complications, new atrial fibrillation, and ventricular fibrillation. In multivariable analysis, bleeding was associated with a significantly higher mortality (hazard ratio: 2.11; 95% confidence interval: 1.63 to 2.75; p < 0.0001). Treatment with active mechanical support by extracorporeal membrane oxygenation or Impella emerged as the major risk factor for bleeding., Conclusions: Risk of bleeding in infarct-related cardiogenic shock is high and associated with increased mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the prognostic value of the SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) scores in patients undergoing percutaneous coronary intervention (PCI) for multivessel coronary disease with infarct-related cardiogenic shock (CS)., Background: The prognostic value of the SYNTAX score in this high-risk setting remains unclear., Methods: The CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial was an international, open-label trial, where patients presenting with infarct-related CS and multivessel disease were randomized to a culprit-lesion-only or an immediate multivessel PCI strategy. Baseline SYNTAX score was assessed by a central core laboratory and categorized as low SYNTAX score (SS ≤22), intermediate SYNTAX score (2232). Adjudicated endpoints of interest were the 30-day risk of death or renal replacement therapy (RRT) and 1-year death. Associations between baseline SYNTAX score and outcomes were assessed using multivariate logistic regression., Results: Pre-PCI SYNTAX score was available in 624 patients, of whom 263 (42.1%), 207 (33.2%) and 154 (24.7%) presented with low, intermediate and high SYNTAX score, respectively. A stepwise increase in the incidence of adverse events was observed from low to intermediate and high SYNTAX score for the 30-day risk of death or RRT and the 1-year risk of death (p < 0.001, for all). After multiple adjustments, intermediate and high SYNTAX score remained strongly associated with 30-day risk of death or renal replacement therapy and 1-year risk of all-cause death. There was no significant interaction between SYNTAX score and the coronary revascularization strategy for any outcomes., Conclusions: In patients presenting with multivessel disease and infarct-related CS, the SYNTAX score was strongly associated with 30-day death or RRT and 1-year mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease (MVD), recent studies have demonstrated the superiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions compared to culprit lesion treatment-only therapy. FFR- and angio-guided PCI have however never been compared in STEMI patients., Trial Design: FLOWER-MI is an open-label multicenter national randomized clinical trial. The aim is to investigate FFR-guided complete revascularization in comparison to angio-guided complete revascularization in STEMI patients with successful PCI of the culprit lesion and ≥50% stenosis in at least one additional non-culprit lesion requiring PCI. Eligible patients will be randomized after successful primary PCI in a 1:1 fashion to either FFR-guided or angio-guided complete revascularization during the index procedure or a staged procedure before discharge (≤5 days). Patients assigned to FFR guidance first have FFR measured in each non-culprit vessel and only undergo PCI if FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac events, including all-cause death, non-fatal MI, and unplanned hospitalization leading to urgent revascularization at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, and 3-year outcomes. Based on estimated event rates, a sample size of 1170 patients is needed to show superiority of the FFR-guided revascularization with 80% power., Conclusion: The aim of FLOWER-MI trial is to assess whether FFR-guided complete revascularization in the acute setting is superior angio-guided complete revascularization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention., Background: Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms., Methods: CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment., Results: Detection of LOF alleles resulted in adjustment of P2Y 12 inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups., Conclusions: In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Women are more likely to suffer and die from cardiogenic shock (CS) as the most severe complication of acute myocardial infarction. Data concerning optimal management for women with CS are scarce. Aim of this study was to better define characteristics of women experiencing CS and to the influence of sex on different treatment strategies., Methods: In the CULPRIT-SHOCK trial (The Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock), patients with CS complicating acute myocardial infarction and multivessel coronary artery disease were randomly assigned to one of the following revascularization strategies: either percutaneous coronary intervention of the culprit-lesion-only or immediate multivessel percutaneous coronary intervention. Primary end point was composite of death from any cause or severe renal failure leading to renal replacement therapy within 30 days. We investigated sex-specific differences in general and according to the revascularization strategies., Results: Among all 686 randomized patients included in the analysis, 24% were women. Women were older and had more often diabetes mellitus and renal insufficiency, whereas they had less often history of previous acute myocardial infarction and smoking. After 30 days, the primary clinical end point was not significantly different between groups (56% women versus 49% men; odds ratio, 1.29 [95% CI, 0.91-1.84]; P =0.15). There was no interaction between sex and coronary revascularization strategy regarding mortality and renal failure ( P =0.11). The primary end point occurred in 56% of women treated by the culprit-lesion-only strategy versus 42% men, whereas 55% of women and 55% of men in the multivessel percutaneous coronary intervention group.interaction =0.11). The primary end point occurred in 56% of women treated by the culprit-lesion-only strategy versus 42% men, whereas 55% of women and 55% of men in the multivessel percutaneous coronary intervention group., Conclusions: Although women presented with a different risk profile, mortality and renal replacement were similar to men. Sex did not influence mortality and renal failure according to the different coronary revascularization strategies. Based on these data, women and men presenting with CS complicating acute myocardial infarction and multivessel coronary artery disease should not be treated differently. However, further randomized trials powered to address potential sex-specific differences in CS are still necessary. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549.