BACKGROUND:Complete coronary-artery revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the preferred strategy for identifying nonculprit lesions that warrant treatment remains uncertain. METHODS:In this international, randomized trial, we assigned patients with STEMI and multivessel disease in whom the culprit lesion had been successfully treated to undergo complete coronary-artery revascularization guided by functional coronary angiography (physiology-guided group) or by conventional angiography (angiography-guided group). The primary outcome was a composite of death from any cause, myocardial infarction, cerebrovascular accident (stroke or transient ischemic attack), or ischemia-driven revascularization, assessed in a time-to-event analysis. The primary safety outcome was a composite of contrast-associated acute kidney injury or major bleeding. RESULTS:A total of 1823 patients underwent randomization; 913 were assigned to the physiology-guided group and 910 assigned to the angiography-guided group. The median age of the patients was 66 years (interquartile range, 58 to 76), and 24% were women. At a median follow-up of 17.9 months, a primary-outcome event had occurred in 81 patients (8.9%) in the physiology-guided group and in 125 patients (13.7%) in the angiography-guided group (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.83; P<0.001). A primary-safety-outcome event occurred in 42 patients (4.6%) in the physiology-guided group and in 65 patients (7.1%) in the angiography-guided group (hazard ratio, 0.63; 95% CI, 0.43 to 0.93; P = 0.02). CONCLUSIONS:In patients with STEMI and multivessel coronary artery disease, a strategy of complete coronary-artery revascularization guided by functional coronary angiography resulted in a lower risk of a primary-outcome event (death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization) than a strategy guided by conventional angiography. (Funded by the Italian Health Ministry and others; AIR-STEMI ClinicalTrials.gov number, NCT05818475.).

Graphical AbstractCentral Illustration. Primary endpoint was a composite of cardiac death, MI, or definite/probable stent thrombosis. BP-EES: biodegradable-polymer everolimus-eluting stent; CI: confidence interval; CV: cardiovascular; DAPT: dual antiplatelet therapy; HBR: high bleeding risk; HR: hazard ratio; MI: myocardial infarction; PCI: percutaneous coronary intervention; TLF: target lesion failure.For image description, please refer to the figure legend and surrounding text.

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.

No data are available on the pharmacodynamic and pharmacokinetic profile of a low dose of ticagrelor as alternative to its standard dose during the early phase after acute coronary syndrome (ACS) according to diabetic status. We reported a post-hoc analysis of a randomized, crossover trial (NCT04739384) comparing ticagrelor 60 vs. 90 mg in elderly patients with ACS according to the presence or absence of diabetes. The primary endpoint was the pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA) at 14 days after treatment with ticagrelor 60 or 90 mg twice daily. Out of 50 patients, 24 (48 What is the key research question? What is new? How might this study influence clinical practice?

BACKGROUND:Complex percutaneous coronary intervention (PCI) is increasingly performed among patients undergoing myocardial revascularisation. AIMS:We conducted a systematic review and meta-analysis to evaluate the association between complex PCI and the risk of ischaemic and bleeding outcomes. METHODS:Hazard ratios (HRs) were pooled using a random-effects model within a Bayesian framework. The primary analysis was restricted to studies providing adjusted risk estimates, whereas the secondary analysis included unadjusted risk estimates. The primary outcomes were myocardial infarction and major bleeding. The secondary outcomes were all-cause death, stent thrombosis, cardiovascular death, target lesion or vessel revascularisation, and stroke. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for prognostic studies was used to determine the level of certainty in the association between complex PCI and the risk of events. RESULTS:We included 290,039 patients, of whom 94,633 (33%) underwent complex PCI. Compared with non-complex PCI, patients undergoing complex PCI had a higher risk of myocardial infarction (adjusted HR 1.71, 95% credible interval [CrI]: 1.49-1.96), major bleeding (adjusted HR 1.24, 95% CrI: 1.14-1.35), all-cause death (adjusted HR 1.21, 95% CrI: 1.12-1.32), cardiovascular death (adjusted HR 1.29, 95% CrI: 1.15-1.46), stent thrombosis (adjusted HR 1.76, 95% CrI: 1.49-2.14), target lesion or vessel revascularisation (adjusted HR 1.99, 95% CrI: 1.58-2.50), and stroke (adjusted HR 1.21, 95% CrI: 1.03-1.42). The posterior probability of a higher risk associated with complex versus non-complex PCI was >99% for all study outcomes. Except for stroke (which was low certainty), the certainty of evidence was moderate to high for all other outcomes. Secondary analysis, including unadjusted risk estimates, provided consistent results. CONCLUSIONS:Patients undergoing complex PCI have an increased risk of both ischaemic and bleeding events compared with patients undergoing non-complex PCI (PROSPERO: CRD420250656254).

BACKGROUND:Patients at high bleeding risk (HBR) presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI) have competing hazards of ischemic and bleeding events. In unselected ACS populations, trials of unguided de-escalation of P2Y12 inhibition reduce bleeding without excess ischemia; however, HBR patients were largely underrepresented in these studies. Comparative evidence across multiple de-escalation regimens in this vulnerable cohort is currently lacking. STUDY DESIGN:DESC-HBR is a prospective, multicenter, randomized, open-label trial with blinded endpoint adjudication enrolling 200 HBR patients (PRECISE-DAPT ≥25 or ARC-HBR criteria) at 30 ± 7 days after ACS-PCI. Following one month of dual antiplatelet therapy (DAPT) with prasugrel 10 mg once daily or ticagrelor 90 mg twice daily, on a background of aspirin 100 mg, patients are randomized (1: 1:1:1) to clopidogrel 75 mg once daily, prasugrel 5 mg once daily, ticagrelor 60 mg twice daily, or continuation of full-dose potent therapy. The primary endpoint is the proportion of patients achieving optimal platelet reactivity (VerifyNow PRU 85-208) at 14 ± 2 days post-randomization, 2-h after maintenance dose. Key secondary outcomes include BARC bleeding, net adverse clinical events, quality of life and adherence. Pharmacodynamic profiling incorporates VerifyNow and Total Thrombus Formation Analysis (T-TAS). A total sample of 200 patients allows >80% power to detect superiority of each de-escalation arm versus control (α = 0.017). CONCLUSIONS:DESC-HBR is the first randomized trial directly comparing multiple P2Y12 inhibitor de-escalation strategies in HBR patients post-ACS. By integrating pharmacodynamic, clinical, and patient-reported outcomes, it will provide information to guide individualized antiplatelet strategies balancing ischemic protection and bleeding mitigation in HBR patients. CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER:NCT05903976, EudraCT 2023-000029-10.

BACKGROUND:The role of beta-blockers in the management of uncomplicated arterial hypertension remains a subject of clinical debate. While beta-blockers are established cornerstones for heart failure and post-myocardial infarction care, their independent efficacy in reducing major adverse cardiovascular events (MACE) in patients without these compelling indications is less clear. This study aimed to evaluate the association between beta-blocker use and MACE in a real-world hypertensive population without prevalent cardiovascular diseases. METHODS:We analyzed 6,702 hypertensive patients from the Campania Salute Network (CSN) registry without prevalent coronary or cerebrovascular disease, valvular heart disease, or heart failure. The association between beta-blocker use and MACE was assessed using three statistical approaches: multivariable-adjusted Cox proportional hazards regression, propensity score matching (PSM), and overlap weighting (OW). An intention-to-treat (ITT) analysis was performed based on baseline prescription, and an exploratory per-protocol (PP) sensitivity analysis was conducted to evaluate the role of sustained treatment adherence. RESULTS:At baseline, 18.1% (n=1,247) of patients were receiving a beta-blocker. Over a median follow-up of 52 months, 308 MACE (4.5%) occurred. After multivariable adjustment and weighting, beta-blocker use was not associated with a lower risk of MACE in the ITT population (Adjusted hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.86-1.52; PSM HR 1.18, 95% CI 0.82-1.70; OW HR 1.10, 95% CI 0.82-1.46). In the exploratory PP sensitivity analysis, even among adherent patients, beta-blocker therapy was not associated with a lower risk of MACE. Conversely, adherence to renin-angiotensin system inhibitors and statins was associated with a lower risk of MACE. Beta-blocker users also exhibited a higher prevalence of metabolic risk factors, including elevated triglycerides, glycemia, and uric acid levels. CONCLUSIONS:In patients with uncomplicated hypertension, beta-blocker use was not associated with a lower risk of MACE, regardless of treatment adherence. These findings are consistent with clinical guidelines that prioritize non-beta-blocker regimens and recommend using beta-blockers in the presence of compelling indications.

Chronic coronary syndromes (CCS) are the most common clinical manifestation of coronary atherosclerosis. Coronary computed tomography angiography (CCTA) is a recent innovation in non-invasive cardiac imaging. It is the only anatomical imaging method that allows direct visualization of the coronary lumen, vessel walls, and atherosclerotic plaques, offering high sensitivity and a strong negative predictive value. CCTA is particularly useful in identifying or ruling out coronary atherosclerosis in the context of CCS and serves as an excellent filter for invasive coronary angiography. Compared to other non-invasive functional imaging tests (stress echocardiography, single photon emission computed tomography, magnetic resonance imaging, positron emission tomography), CCTA provides detailed characterization of both obstructive and non-obstructive plaques, enabling accurate risk stratification and guiding therapy. Recent advances in computed tomography technology and imaging techniques further extend the use of CCTA beyond plaque and stenosis evaluation, offering also functional lesion information. This consensus document aims to detail the technical aspects of CCTA and illustrate its role in optimizing CCS diagnostic and therapeutic management, enhancing precision medicine and personalized patient care.

BACKGROUND:In high-bleeding-risk (HBR) patients undergoing percutaneous coronary intervention (PCI), shortening dual antiplatelet therapy (DAPT) is essential, but the optimal approach in those requiring oral anticoagulation (OAC) is uncertain. We evaluated a 1-month dual antithrombotic regimen in HBR patients with and without OAC indication in a prespecified sub-analysis of the POEM trial. METHOD:POEM enrolled HBR patients treated with a bioresorbable polymer everolimus-eluting stent. Patients were stratified by OAC indication: the non-OAC group (n = 281) received 1-month DAPT followed by single antiplatelet therapy; the OAC group (n = 158) received 1-month OAC plus a P2Y12 inhibitor followed by OAC monotherapy. Time-to-event outcomes were analyzed using the log-rank test, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression models. The primary analysis was conducted according to the intention-to-treat principle. A per-protocol analysis, excluding patients with DAPT duration >1 month, was performed as a sensitivity analysis. RESULTS:At 1 year, the primary endpoint, a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis, occurred in 6.1% of the non-OAC group versus 2.6% of the OAC group (HR 0.41, 95% CI 0.14-1.22; P = .097). Secondary ischemic outcomes were similar. BARC type 3-5 bleeding was infrequent (2.6% vs 1.3%; P = .369). The per-protocol analysis showed consistent results. CONCLUSIONS:In HBR patients after PCI, transition to OAC monotherapy at 1 month was associated with low ischemic and bleeding risks, comparable to single antiplatelet therapy. These findings support early OAC monotherapy as a feasible strategy warranting randomized investigation. TRIAL REGISTRATION:EudraCT Number: 2016-004510-99; clinicaltrials.gov: NCT03112707.

OBJECTIVE:To evaluate sex related differences in the treatment effect of antithrombotic therapy in patients with established coronary artery disease. DESIGN:Systematic review and meta-analysis. DATA SOURCES:Ovid Medline and Embase databases from inception to April 2025. INCLUSION CRITERIA:Included studies were randomised controlled trials reporting sex stratified outcomes, including ischaemic and major bleeding events, and comparing any experimental versus control antithrombotic strategy in coronary artery disease. DATA EXTRACTION AND SYNTHESIS:Two reviewers extracted data and assessed the risk of bias. To avoid ecological bias, a within trial framework was developed to evaluate sex related heterogeneity in the treatment effect of antithrombotic therapies. Sex specific risk estimates were reported as hazard ratios with 95% confidence intervals, whereas trial level ratios of hazard ratios were pooled with an inverse variance model. RESULTS:A total of 33 trials enrolling 274 433 participants, of which 72 601 (median proportion 25%) were women, were included. Patients were enrolled between 1999 and 2025. A total of 6018 deaths occurred in 187 580 patients across 22 trials (3064 deaths in patients using more intensive antithrombotic therapies and 2954 in those using less intensive therapies). The relative risk of all cause death was comparable for more intensive versus less intensive antithrombotic therapies in both women and men, without sex based interaction (interaction hazard ratio 1.06, 95% confidence interval 0.94 to 1.19; P for interaction=0.33; I2=0.00%; P for heterogeneity=0.76). 7558 myocardial infarctions occurred among 172 504 patients. More intensive antithrombotic therapies were associated with a reduced risk of myocardial infarction by ~15% in both men and women (interaction hazard ratio 1.05, 0.95 to 1.17; P for interaction=0.36; I2=14.05%; P for heterogeneity=0.28). Conversely, major bleeding was significantly increased by ~40% for more intensive versus less intensive antithrombotic therapies irrespective of sex (interaction hazard ratio 0.99, 0.86 to 1.15; P for interaction=0.93; I2=33.56%; P for heterogeneity=0.05). Overall, 4003 major bleeding events occurred (2384 in patients using more intensive therapies and 1619 in those using less intensive therapies). CONCLUSIONS:Antithrombotic therapies in patients with established coronary artery disease provided consistent efficacy and safety outcomes in women and men. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42024560908.

BACKGROUND:Few data are available on polymer-free drug-eluting stents in patients undergoing percutaneous coronary intervention (PCI). AIMS:We aimed to determine the efficacy and safety of a polymer-free amphilimus-eluting stent (AES), using a reservoir-based technology for drug delivery, compared with a biodegradable-polymer everolimus-eluting stent (EES). METHODS:This was a randomised, investigator-initiated, assessor-blind, non-inferiority trial conducted at 14 hospitals in Italy (ClinicalTrials.gov: NCT04135989). All-comer patients undergoing PCI were randomly assigned to either polymer-free AES or biodegradable-polymer EES. The primary endpoint was a device-oriented composite endpoint, including cardiovascular death, target vessel myocardial infarction, or target lesion revascularisation at 1-year follow-up. RESULTS:Between January 2020 and June 2022, a total of 2,107 patients with 3,042 coronary lesions were randomised to polymer-free AES (1,051 patients) or biodegradable-polymer EES (1,056 patients). At 1-year follow-up, the primary endpoint occurred in 86 (8.2%) patients randomised to polymer-free AES and 76 (7.2%) patients randomised to biodegradable-polymer EES (risk difference 1%, upper limit of the 1-sided 95% confidence interval [CI] of 2.9%; p for non-inferiority=0.041). There were no significant differences in the incidence of the components of the primary endpoint between groups. However, definite or probable stent thrombosis occurred more frequently in patients randomised to polymer-free stents (1.0% vs 0.3%; hazard ratio 3.72, 95% CI: 1.04-13.33; p=0.044) due to an increased risk of early stent thrombosis within 30 day Conclusions: In all-comer patients undergoing PCI, polymer-free AES were non-inferior to biodegradable-polymer EES at 1-year follow-up in terms of a device-oriented composite endpoint despite being associated with an increased risk of early stent thrombosis.

Intravascular optical coherence tomography (IVOCT) is emerging as an effective imaging technique for accurately characterizing coronary atherosclerotic plaques. This technique provides detailed information on plaque morphology and composition, enabling the identification of high-risk features associated with coronary artery disease and adverse cardiovascular events. However, despite advancements in imaging technology and image assessment, the adoption of IVOCT in clinical practice remains limited. Manual plaque assessment by experts is time-consuming, prone to errors, and affected by high inter-observer variability. To increase productivity, precision, and reproducibility, researchers are increasingly integrating artificial intelligence (AI)-based techniques into IVOCT analysis pipelines. Machine learning algorithms, trained on labelled datasets, have demonstrated robust classification of various plaque types. Deep learning models, particularly convolutional neural networks, further improve performance by enabling automatic feature extraction. This reduces the reliance on predefined criteria, which often require domain-specific expertise, and allow for more flexible and comprehensive plaque characterization. AI-driven approaches aim to facilitate the integration of IVOCT into routine clinical practice, potentially transforming this technique from a research tool into a powerful aid for clinical decision-making. This narrative review aims to (i) provide a comprehensive overview of AI-based methods for analyzing IVOCT images of coronary arteries, with a focus on plaque characterization, and (ii) explore the clinical translation of AI to IVOCT, highlighting AI-powered tools for plaque characterization currently intended for commercial and/or clinical use. While these technologies represent significant progress, current solutions remain limited in the range of plaque features these methods can assess. Additionally, many of these solutions are confined to specific regulatory or research settings. Therefore, this review highlights the need for further advancements in AI-based IVOCT analysis, emphasizing the importance of additional validation and improved integration with clinical systems to enhance plaque characterization, support clinical decision-making, and advance risk prediction.

OBJECTIVES:Valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) has gained popularity as a less invasive alternative to a redo surgical aortic valve replacement (redo-SAVR); which one is the preferred technique in these cases, however, remains a topic of debate, as the available data refer to retrospective studies with few patients or limited follow-up. The present metanalysis aimed to compare the short-term and long-term outcomes of the two techniques in the setting of a failed surgical bioprosthesis. METHODS:PubMed, MEDLINE, and Embase were searched on 10 November 2023 yielding 355 results (PROSPERO ID: CRD42023490612), of which 27 were suitable for meta-analysis. The primary outcomes were short-term and long-term all-causes and cardiovascular mortality. Logarithmic risk ratio (Log RR) and mean difference were used for categorical and continuous data, respectively. RESULTS:Both redo-SAVR and ViV-TAVI exhibited similar procedural and short-term mortality. However, ViV-TAVI demonstrated lower 1-year mortality [RR: 0.74, 95% confidence interval (CI) (0.57-0.96), P = 0.02], acute kidney injury (RR: 0.47, P < 0.001), bleeding (RR: 0.44, P < 0.001), stroke (RR: 0.70, P < 0.05), and new pacemaker implantation (RR: 0.69, P < 0.05). Conversely, redo-SAVR demonstrated more favorable mean postoperative aortic valve gradients [mean difference 2.59, 95% CI (0.86-4.31), P < 0.01]. CONCLUSION:Short-term mortality was similar between the groups, but ViV-TAVI showed better survival at 1 year as well as reduced rates of acute kidney injury, bleeding, stroke, and pacemaker implantation. However, redo-SAVR leads to a better hemodynamic profile. Even if collected data come from retrospective studies, the present results could help to guide the choice of the best approach case-by-case according to the patient's clinical profile.