BACKGROUND:The universal definition of percutaneous coronary intervention (PCI)-related myocardial infarction (MI) has been substantially updated over the years, including an increase in the biomarker threshold (from 3 to 5 times the upper reference limit) and the introduction of ancillary criteria such as ischemic symptoms and electrocardiographic or angiographic complication. The impact of these changes in patients with acute coronary syndrome (ACS) remains incompletely understood. The objective of this study was to compare prognostic implications of evolving universal definitions of PCI-MI in a large cohort of patients with ACS from the MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX). METHODS:Among 6724 patients undergoing PCI in the MATRIX trial, PCI-MI was prospectively adjudicated by the second, third and fourth universal definition of MI (UDMI). The 2 co-primary end points were all-cause and cardiovascular death (from 24 hours to 1 year after PCI) in patients with non-ST-segment-elevation ACS. Hazard ratios and 95% CIs were generated for primary and secondary end points with the use of Cox proportional hazards time-to-event analyses for each MI definition. RESULTS:PCI-MI occurred in 590 patients (9%) with the second UDMI, 193 (3%) with the third UDMI, and 182 (3%) with the fourth UDMI applied in the overall ACS population. Among patients with non-ST-segment-elevation ACS, the corresponding figures were 15%, 5%, and 5%. Only PCI-MI defined by the fourth UDMI in patients with non-ST-segment-elevation ACS was associated with increased risks of all-cause (hazard ratio, 2.08 [95% CI, 1.00-4.30]; P=0.048) and cardiovascular (hazard ratio, 2.62 [95% CI, 1.03-6.65]; P=0.043) death. In patients with ST-segment-elevation myocardial infarction, PCI-MI was uncommon (1% to 4% depending on the working definition) and was not associated with increased mortality. In the absence of objective ancillary criteria (electrocardiographic and angiographic complications), isolated troponin elevations up to 20 times the upper reference limit were not associated with increased mortality risk. CONCLUSIONS:PCI-MI defined according to the fourth UDMI was associated with increased risks of 1-year mortality only in patients with non-ST-segment-elevation ACS. These data support the evolution of the universal definition of PCI-MI. REGISTRATION:URL: http://www.clinicaltrials.gov; Unique identifier: NCT01433627.

BACKGROUND:Risk stratification in acute pulmonary embolism (PE) is essential to guide clinical management, particularly regarding the need for escalated therapies. Despite the availability of several prognostic scores, their comparative performance in unselected PE populations remains uncertain. OBJECTIVES:To compare the prognostic performance of six widely used risk assessment tools for acute PE in predicting short-term outcomes. METHODS:We retrospectively collected data from 397 consecutive patients with acute PE from a single institutional registry. Six risk scores (modified Bova, modified FAST, CPES, NEWS-2, PESI, and sPESI) were calculated at admission. The primary endpoint was the composite of in-hospital PE-related death, need for rescue thrombolysis, or severe hemodynamic instability. Secondary endpoints were the individual components of the primary endpoint and all-cause mortality up to 3 months. RESULTS:The primary endpoint occurred in 48 patients (12.1%), including PE-related death in 25 (6.3%), severe hemodynamic instability in 25 (6.3%), and systemic thrombolysis in 6 (1.5%). In-hospital mortality was 13.1% (n=52), and 3-month all-cause mortality was 16.4% (n=65). The PESI score demonstrated the highest predictive performance for all outcomes (AUC for the primary endpoint: 0.84, 95% confidence interval: 0.78-0.90), followed by NEWS-2 and sPESI. PESI and NEWS-2 consistently showed the greatest improvement over ESC classification in terms of net reclassification and increased discrimination. Bootstrap-based ranking confirmed PESI as the most likely best-performing score, while modified Bova, FAST, and CPES showed inferior performance. Findings were consistent across all ESC risk strata. CONCLUSIONS:Among commonly used prognostic scores for acute PE, PESI and NEWS-2 provide superior discrimination for short-term clinical outcomes and incremental value over ESC-based stratification. These scores may aid in refining risk assessment and guiding management in acute PE.

AIMS:Patients at high bleeding risk (HBR) and acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) are at high risk of adverse outcomes. We investigated the clinical outcomes and their consistency after biodegradable polymer sirolimus-eluting (BP-SES) or durable polymer zotarolimus-eluting stent (DP-ZES) implantation in HBR patients with or without ACS. METHODS AND RESULTS:The per-protocol population of the BIOFLOW-DAPT randomized control trial (RCT) consisted of HBR patients with (n = 541) or without ACS (n = 1245) who were randomized to BP-SES or DP-ZES and underwent 1 month dual antiplatelet therapy (DAPT). The primary efficacy and safety endpoints were target lesion failure (TLF), defined as the composite endpoint of cardiac death, target vessel myocardial infarction (TV-MI), or clinically driven target lesion revascularization (cd-TLR) as well as major bleeding defined as BARC 3 or 5 (according to Bleeding Academic Research Consortium classification) and definite/probable stent thrombosis (ST). At 1 year, patients with ACS suffered from higher cardiac death rates (3.4 vs. 1.3%, log-rank P = 0.004) but similar TLF (6.8 vs. 6.7%, P = 0.992), TV-MI (2.8 vs. 4.5%, P = 0.100), cd-TLR (1.4 vs. 2.1%, P = 0.300), major bleeding (4.2 vs. 3.1%, P = 0.266), and ST (0.2 vs. 0.9%, P = 0.098) compared with no ACS patients. The rate of TLF and of all secondary endpoints was consistent with BP-SES or DP-ZES across ACS strata. CONCLUSION:HBR patients with ACS are at higher risk of cardiac death than those without ACS and experience a consistent outcome with BP-SES or DP-ZES followed by 1 month DAPT at 1 year follow-up. CLINICAL TRIAL REGISTRATION:NCT04137510.

BACKGROUND:Patients are at increased risk for recurrent ischemic events after an acute coronary syndrome event. Milvexian, an oral factor XIa inhibitor, may reduce the risk of major adverse clinical events with minimal bleeding risk. METHODS:In this phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of milvexian when added to standard antiplatelet therapy within 7 days after an acute coronary syndrome event. Patients were assigned in a 1:1 ratio to receive oral milvexian (25 mg twice daily) or matched placebo. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke as evaluated in a time-to-event analysis. The principal safety outcome was Bleeding Academic Research Consortium (BARC) type 3c or 5 bleeding (intracranial or intraocular bleeding that compromises vision or fatal bleeding). RESULTS:After a planned interim analysis that was based on 556 adjudicated efficacy end points, the trial was terminated for futility. A total of 14,194 patients had been enrolled, with 7094 assigned to receive milvexian and 7100 to receive placebo. After a median follow-up of 12.2 months, a primary efficacy outcome event had occurred in 384 patients (5.4%) in the milvexian group and in 365 patients (5.1%) in the placebo group (hazard ratio, 1.05; 95% confidence interval, 0.91 to 1.21; P = 0.50). BARC type 3c or 5 bleeding occurred in 23 patients (0.3%) in the milvexian group and in 22 patients (0.3%) in the placebo group (P = 0.88). CONCLUSIONS:Among patients with a recent acute coronary syndrome event, milvexian did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke but did not increase the risk of intracranial or fatal bleeding, as compared with placebo. (Funded by Janssen Research and Development and Bristol Myers Squibb; LIBREXIA ACS ClinicalTrials.gov number, NCT05754957.).

This systematic review and meta-analysis evaluates the safety and efficacy of abbreviated dual antiplatelet therapy durations in patients at high bleeding risk undergoing percutaneous coronary intervention. QuestionAmong patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI), is an abbreviated dual antiplatelet therapy (DAPT) regimen safer and as effective as standard DAPT duration?FindingsIn this systematic review and meta-analysis of 14 randomized clinical trials, including 11 398 patients at HBR, abbreviated DAPT (1-month to 3-month) was associated with significantly lower bleeding risk compared with standard DAPT (6-month to 12-month). In comparisons with standard DAPT, abbreviated regimens were not associated with an increase in major adverse cardiovascular events, and an increased risk of major adverse cardiovascular events was observed with 1 vs 3 months of DAPT in the single trial comparing these 2 regimens, but the network estimate was nonsignificant.MeaningIn this meta-analysis, abbreviated DAPT was associated with less bleeding and, at least for 3-month regimens, was not associated with an increase in ischemic risk in patients at HBR undergoing PCI. ImportanceThe optimal duration of dual antiplatelet therapy (DAPT) in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) remains uncertain.ObjectivesTo evaluate the safety and efficacy of abbreviated DAPT durations in patients at HBR undergoing PCI.Data SourcesPubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to October 26, 2025.Study SelectionRandomized clinical trials (RCTs) comparing abbreviated (ie, 1- to 3-month) vs standard (ie, 6- to 12-month) DAPT durations in patients at HBR without an indication for oral anticoagulation.Data Extraction and SynthesisA pairwise meta-analysis was performed to compare abbreviated (ie, 1-month to 3-month) vs standard (ie, >= 6-month) DAPT durations. A frequentist network meta-analysis was performed to compare 1-month, 3-month, and standard DAPT.Main Outcomes and MeasuresThe coprimary safety and efficacy end points were major or clinically relevant nonmajor bleeding (MCRB) and major adverse cardiovascular events (MACE; ie, a composite of cardiovascular death, myocardial infarction, or stroke).ResultsA total of 14 RCTs encompassing 11 398 patients at HBR (mean [range] age, 74.7 [68.6-80.0] years; 39.1% female and 60.9% male) were included. Compared with standard DAPT, abbreviated DAPT was associated with lower MCRB (risk ratio [RR], 0.71; 95% CI, 0.55-0.92; P = .009) and major bleeding (RR, 0.76; 95% CI, 0.59-0.99; P = .04). The risks of MACE (RR, 0.97; 95% CI, 0.81-1.16; P = .76) and its individual components did not differ between abbreviated and standard regimens. An increased risk of MACE was observed with 1-month vs 3-month DAPT in the single trial comparing these regimens, but the network estimate was nonsignificant (RR, 1.28; 95% CI, 0.96-1.72).Conclusions and RelevanceIn this systematic review and meta-analysis, for patients at HBR undergoing PCI, abbreviated DAPT was associated with a lower risk of bleeding and, at least for 3-month regimens, was not associated with an increase in fatal or nonfatal ischemic cardiovascular or cerebrovascular events compared with standard 6- to 12-month DAPT.

AIMS:In patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI), abbreviated dual antiplatelet therapy (DAPT) has been shown to reduce bleeding without increasing ischemic risk. However, the optimal duration in specific subgroups, particularly anemic patients, remains unclear and was the focus of this analysis. METHODS:This study included 3,364 HBR patients from three prospective trials in the XIENCE Short DAPT Program who underwent PCI with cobalt-chromium everolimus-eluting stents. Anemia was defined as Hb <11 g/dL. The primary endpoint was all-cause death or myocardial infarction; secondary endpoints included BARC 2-5 and 3-5 bleeding. Outcomes by DAPT duration (1 vs 3 months), defined according to study protocol, were assessed using propensity score stratification. RESULTS:Anemia was present in 514 patients (15.3%). At 1 year, anemic patients experienced higher rates of both ischemic and bleeding events compared with non-anemic patients. Among anemic patients, ischemic outcomes were similar with 1- and 3-month DAPT (15.7% vs 16.3%; adjusted hazard ratio [adjHR] 0.94, 95% confidence interval [CI] 0.59-1.52; p=0.807), whereas 1-month DAPT was associated with a lower incidence of major bleeding (6.1% vs 11.1%; adjHR 0.49, 95% CI 0.24-1.00; p=0.050). In non-anemic patients, ischemic and bleeding outcomes were similar irrespective of DAPT duration. CONCLUSIONS:Among HBR patients undergoing PCI, abbreviated DAPT was associated with comparable ischemic outcomes regardless of anemia status. In patients with baseline anemia, 1-month DAPT was associated with lower major bleeding without an apparent ischemic trade-off.

Acute myocardial infarction (AMI) remains a major cause of cardiovascular illness and death. Advanced imaging techniques, particularly cardiac magnetic resonance (CMR), have become essential in assessing tissue alterations within the infarcted zone. The CMR published reports focus primarily on evaluating infarct size and the peri-infarct region in the context of AMI. Recent evidence highlights that the noninfarcted myocardium (NIM) surrounding the infarct sustains functional, structural, and inflammatory changes due to ischemic injury. CMR can detect significant changes in the NIM, such as inflammation, interstitial expansion, and altered myocardial deformation. These findings indicate that the NIM is not merely passive but is actively involved in the progression of heart disease after AMI. Targeting the NIM with novel therapeutic strategies, such as antiinflammatory and antifibrotic treatments, shows promise for improving patient outcomes. This review aims to define the role and imaging criteria for exploring the NIM after AMI and to highlight its emerging significance as a tool for risk stratification and a potential therapeutic target.

BACKGROUND:Patients with myocardial infarction and large thrombus burden face greater infarct size and higher mortality, yet no effective therapy exists for this high-risk subgroup. OBJECTIVES:To investigate the effects of stent-retriever thrombectomy in addition to conventional percutaneous coronary intervention (PCI) versus conventional PCI alone on infarct size. METHODS:In this open-label, multicenter, superiority trial, 160 patients with ST-segment elevation myocardial infarction and large thrombus burden at angiography (TIMI thrombus grade ≥3 in infarct-related artery) were consented and 156 randomly assigned to undergo stent-retriever thrombectomy followed by conventional PCI or conventional PCI alone. Primary outcome was infarct size extension assessed by area under the curve (AUC) for creatine kinase (CK)-MB. Safety outcome was major adverse cardiovascular events (MACE; comprising cardiovascular death, nonfatal myocardial infarction, nonfatal stroke), at 3 and 30 days. RESULTS:Infarct size (CK-MB AUC) was lower in the stent-retriever group (n=78) versus the conventional group (n=76) (3965 IU/L·h; interquartile range [IQR] 2480-5092 versus 5250; IQR 3506-7449; difference -1359, 95% CI -2231 to -522; p=0.001). At exploratory cardiac magnetic resonance findings, infarct size was lower in the stent-retriever group (n=64; left ventricle, 17%; IQR 11-28) versus the conventional PCI group (n=59; 28.0%; IQR 18-33; difference -7.0, 95% CI -12 to -2.0), whereas left ventricular volumes and ejection fraction did not differ. There was no MACE at 3 days and 1 at 30 days in the stent-retriever group versus 2 and 3, respectively, in the conventional PCI group. CONCLUSIONS:Stent-retriever thrombectomy followed by conventional PCI in patients with large thrombus burden undergoing primary PCI ≤8 hours of symptom onset was associated with reduced infarct size versus conventional PCI alone.

Antiplatelet therapy is the cornerstone of treatment in patients with established atherosclerotic disease. The use of a single antiplatelet agent is commonly recommended for the long-term management of these patients. Although aspirin has represented the mainstay of antiplatelet therapy for decades, emerging evidence suggests that P2Y₁₂ inhibitors may be more than just a viable alternative to aspirin and may be preferred over aspirin. This review examines the current evidence comparing the efficacy and safety of aspirin vs P2Y12 inhibitors in reducing cardiovascular events in patients with atherosclerotic disease. Special attention is given to the practical challenges and considerations surrounding the use of aspirin vs P2Y12 inhibitor monotherapy, including interindividual variability in drug response, side effects, costs, and real-world implementation. By evaluating the strengths and limitations of these treatment options, this article aims to guide clinicians in optimizing the selection of single antiplatelet strategies for long-term secondary prevention in patients with atherosclerotic disease.

BACKGROUND:Understanding the concomitant evolution of bleeding vs ischemic risk after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) treated with 1-month dual antiplatelet therapy (DAPT) would help optimize dynamic treatment strategies. OBJECTIVES:The aim of this study was to describe the timing of bleeding and ischemic events during 1 year after PCI in this population. METHODS:Timings of major bleeding events and of major adverse cardiovascular events (MACE) were analyzed in patient-level data from 7 prospective studies including HBR patients treated with PCI and 1-month DAPT. RESULTS:Among 7,266 patients (mean age 76 ± 9.0 years, 31.5% women), Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding occurred in 284 (4.0%), with 73 (1.0%) occurring ≤30 days after and 211 (2.9%) >30 days after index PCI. MACE occurred in 433 patients (6.0%), among which 64 (0.9%) occurred ≤30 days after index PCI and 369 (5.1%) after 30 days. During the first 30 days, there was no significant difference between rates of MACE and BARC types 3 to 5 bleeding events (22.3% vs 25.7%; P = 0.407). However, MACE rates were significantly higher than rates of BARC types 3 to 5 bleeding between 31 and 90 days (7.2% vs 4.9%; P = 0.024) and between 91 and 365 days (5.3% vs 3.1%; P < 0.001) CONCLUSIONS: Among HBR patients undergoing PCI treated with 1-month DAPT, the risk for major bleeding and MACE is highest in the first 30 days. MACE remain consistently more frequent than bleeding after the first month, when event rates stabilize over time while on single antiplatelet therapy.

AIMS:Cangrelor is approved for oral P2Y12 inhibitor naïve patients undergoing percutaneous coronary intervention (PCI). Pharmacodynamic (PD) investigations in different clinical settings, using various assays, have shown contrasting data in terms of entity of platelet inhibition and rates of high residual platelet reactivity (HRPR). We assessed the PD effects in patients with or without ST elevation myocardial infarction (STEMI) receiving cangrelor during PCI. METHODS AND RESULTS:The PharmacOdynaMic effects of cangrelor in PatiEnts wIth acute or chronIc coronary syndrome undergoing percutaneous coronary intervention (POMPEII) registry (NCT04790032) is an investigator-initiated, prospective study assessing PD at four time points with three assays. From March 2021 to June 2024, 126 patients naïve from oral P2Y12 inhibitors underwent PCI with cangrelor [32 with STEMI and 94 without (NSTE-ACS = 30, CCS = 64)]. All STEMI patients switched from cangrelor to ticagrelor, while most patients without STEMI switched to clopidogrel. Inhibition of platelet aggregation (IPA%) during cangrelor infusion was lower in patients with STEMI compared with those without STEMI (LTA 20-μM-ADP 51.5 ± 16.2% vs. 59.7 ± 16.2%; P = 0.017). Conversely, after switching from cangrelor to an oral P2Y12 inhibitor, IPA was greater in patients with STEMI compared with those without STEMI. Rates of HRPR were consistent with lower platelet inhibition in STEMI during cangrelor and greater after its discontinuation compared with patients without STEMI. Within STEMI patients, cangrelor-induced IPA was lower compared with ticagrelor-induced IPA (P = 0.036). CONCLUSION:Cangrelor-induced platelet inhibition was lower in patients with STEMI compared with those without STEMI and was lower than that induced by ticagrelor among STEMI patients. The switch from cangrelor to an oral P2Y12 inhibitor exposed patients without STEMI to greater HRPR compared with those with STEMI.

AIMS:Guidelines recommend immediate invasive management for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients meeting very high-risk (VHR) criteria. Whether these criteria identify occlusion myocardial infarction (OMI) and expedite reperfusion is uncertain. METHODS AND RESULTS:This post-hoc analysis included 2979 NSTE-ACS patients undergoing percutaneous coronary intervention (PCI) in the MATRIX programme with available culprit-lesion flow. OMI was defined as culprit-vessel TIMI flow 0-1. We evaluated European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) VHR criteria for OMI detection and time from first medical contact (FMC) to PCI. OMI occurred in 592 patients (19.9%). At least one VHR criterion was present in 52.9% according to ESC and 14.1% according to ACC/AHA definitions. Among patients with OMI, only 58.1% fulfilled ESC and 24.1% ACC/AHA criteria. Median FMC-to-PCI time was shorter in patients fulfilling ESC criteria (27.0 vs. 40.5 h) or ACC/AHA VHR criteria (12.2 vs. 69.9 h; both P < 0.001). Nevertheless, PCI within 2 h occurred in only 2.6% and 7.7% of patients meeting ESC and ACC/AHA criteria, respectively, and in 3.6% of patients with OMI. Even among OMI patients fulfilling VHR criteria, timely reperfusion within 2 h occurred only 4.7% and 9.9%. CONCLUSION:Guideline-directed VHR criteria had limited sensitivity for OMI and rarely translated into guideline-recommended immediate PCI. Current NSTE-ACS classification and triage strategies require reconsideration to improve recognition and timely reperfusion of acute coronary occlusion.

Drug eluting stents (DES) are the standard treatment for percutaneous coronary intervention (PCI) in real-world clinical practice. However, the implantation of DES is associated with significant limitations, such as the development of neo-atherosclerosis and a persistent risk of stent failure during mid- and long-term follow-up. Currently, dual antiplatelet therapy (DAPT) after stent implantation is required for at least 1 month, with the majority of patients receiving DAPT treatment for 6 to 12 months, which carries an inherent increased risk of bleeding complications. Drug-coated balloons (DCB) are alternative to DES in some lesion settings, such as in-stent restenosis or small coronary artery disease (CAD), with promising initial results also in other clinical or lesion settings, such as acute coronary syndromes, de novo lesions and complex CAD. Although the safety of DCB has been shown in several studies, the optimal regimen and duration of antiplatelet therapy (APT) after DCB treatment remain unclear. In this study, we review the current evidence on protocol-mandated antiplatelet therapies across DCB studies and propose an antiplatelet algorithm for patients with CAD treated with DCB.

Bleeding is a prevalent and frequently serious complication of anticoagulant therapy. The use of oral anticoagulants to prevent thrombotic events in common cardiovascular conditions, such as atrial fibrillation, exposes patients to an increased risk of bleeding which is associated with morbidity and mortality. The consequences of bleeding extend well beyond the acute event, affecting treatment adherence, long-term management decisions, and increasing the risk of ischaemic events when anticoagulation is discontinued. Optimizing the balance between thrombotic and bleeding risk requires expertise in risk stratification, preventive strategies, acute management, and the appropriate timing of anticoagulation resumption after haemostasis. This review summarizes the epidemiology and clinical impact of bleeding in patients receiving oral anticoagulant therapy and provides contemporary, patient-centred flowcharts for acute management and safe resumption of treatment. Future efforts should focus on refining risk prediction, individualizing anticoagulant regimens, and improving access to targeted reversal agents to further improve patient outcomes.