American heart journal最新文献

Background: The completeness of revascularization in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) remains understudied. The SLIM trial previously demonstrated a significant reduction in a composite endpoint of all-cause death, non-fatal myocardial infarction (MI), repeat revascularization, and stroke with complete revascularization under a frequentist framework. This post-hoc Bayesian re-analysis offers a probabilistic interpretation beyond conventional significance testing.

Methods: The primary composite endpoint was analyzed as in the original trial, while secondary endpoints of the composite were evaluated individually. Analyses under multiple priors assessed robustness. The minimal clinically important difference (MCID) was defined as 5% absolute risk difference (ARD) for the composite endpoint and 1% for individual endpoints. The primary model used a weakly informative prior on the log relative risk (RR) scale within a normal-normal Bayesian framework.

Results: 478 patients were randomized (complete: n=240; culprit-only: n=238). The posterior median RR for the composite endpoint was 0.41 (95% credible interval [CrI] 0.22-0.76), corresponding to an ARD of -7.9% (95%CrI -10.4% to -3.2%). The probability of any benefit was 99.8%, and the probability of meeting the MCID was 91.2%. For repeat revascularization, the ARD was -8.3% (95%CrI -10.0% to -4.5%), with a >99.9% probability of clinically relevant benefit. For non-fatal MI, the ARD was -2.8% (95%CrI -4.2% to 0.9%), with a 94.8% probability of benefit. Results were consistent across all priors.

Conclusion: Complete revascularization provides a high probability of clinically meaningful benefit in NSTEMI patients with MVD, primarily through reductions in non-fatal MI and repeat revascularization.

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 one 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.

Introduction: Catheter-based interventions (CBI) have yielded promising data in selected patients with acute pulmonary embolism (PE). Despite growing clinical use, high-quality comparative evidence on the efficacy and safety of CBI, especially in relation to standard anticoagulation or systemic thrombolysis, is limited. As new randomized controlled trials (RCTs) rapidly accumulate, this living evidence synthesis will aim to systematically and continuously evaluate the comparative efficacy and safety of reperfusion strategies versus standard of care in patients with high- and intermediate-risk acute PE.

Methods and analysis: This living systematic review and meta-analysis will include RCTs comparing reperfusion strategies to standard of care in adult patients with high- or intermediate-risk PE. The primary analysis will pertain to trials that are powered and designed to assess hard clinical outcomes, such as death and hemodynamic deterioration. A secondary analysis will include additional studies reporting clinical outcomes, including those primarily evaluating hemodynamic or surrogate outcomes. Analyses will be stratified by PE severity (high- and intermediate-risk) and also conducted using a frequentist network meta-analysis framework. The review is ongoing, with new eligible trials added prospectively. As of the initial search on 28 May 2025, 23 RCTs are included. Thirteen additional ongoing trials were identified for future inclusion, including trials with clinical outcomes such as PEITHO-3, HI-PEITHO, PEERLESS II, PE-TRACT, and PRAGUE-26 for intermediate-risk PE, and CATCH-PE II, PERSEVERE, and TORPEDO-NL for high-risk PE.

Conclusion: This living meta-analysis will offer continuously updated, comparative evidence on reperfusion strategies for acute PE, with a focus on informing the role of catheter-based interventions in clinical decision-making.

Registration: PROSPERO: CRD420251207053. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251207053.

Background: Atrial fibrillation (AF) may progress from paroxysmal AF (PAF) to more persistent forms, but the underlaying mechanisms are not well understood. The aim of this study was to assess the association between atherosclerosis and AF progression in patients with PAF.

Methods: In this substudy of RACE V, 612 patients with PAF underwent extensive phenotyping at baseline and continuous rhythm monitoring. The association between atherosclerosis and AF progression was investigated.

Results: The median age was 64 (57-70) years, 257 (42%) were women, and the median CHA₂DS₂-VA score was 2 (1-3). At baseline, 395 (65%) patients had atherosclerosis, defined by carotid/coronary imaging and/or history of vascular disease. Patients with atherosclerosis were older, had higher waist circumference, more hypertension, and lower eGFR than patients with no atherosclerosis. During a median of 3.4 (2.8-3.7) years follow-up, 108 (18%) patients had AF progression. The presence of atherosclerosis was associated with increased progression (21% vs. 12%; p = 0.004). In univariable analyses, atherosclerosis was a determinant of AF progression (OR: 2.04; 95% CI: 1.28-3.37; p = 0.004), and the association persisted following adjustment for established risk factors (OR: 2.23; 95% CI: 1.10-4.89; p = 0.034).

Conclusions: In patients with paroxysmal AF, 65% of patients had atherosclerosis. Atherosclerosis was a determinant of AF progression after adjustment for established risk factors and comorbidities, suggesting that vascular disease may contribute directly to atrial remodelling and arrhythmia persistence.

Background: Both percutaneous left atrial appendage occlusion (LAAO) and non-vitamin K antagonist oral anticoagulants (NOACs) are noninferior to warfarin for stroke prevention in high-risk patients with atrial fibrillation (AF). However, there is limited data comparing LAAO with NOACs. The CATALYST trial compares a dual-seal LAAO device (Amplatzer™ Amulet™) to NOACs in AF patients indicated for thromboprophylaxis.

Study design: CATALYST is a prospective, multicenter, randomized controlled, open-label trial with an adaptive statistical design. Up to 2,650 AF patients with CHA₂DS₂-VASc score ≥2 (men) or ≥3 (women) will be randomly assigned to LAAO or NOAC at 123 global sites. Patients randomized to NOACs take the appropriate labeled dose with compliance monitored at each visit, while LAAO patients receive dual antiplatelet therapy followed by aspirin monotherapy for ≥12 months post-implant. Patients are followed through 5 years, with post-implant cardiac imaging at 3- and 12-months. There are three co-primary endpoints: (1) ischemic stroke, systemic embolism, or cardiovascular death through 2 years, tested for noninferiority; (2) major or clinically relevant non-major bleeding through 2 years, tested for superiority; and (3) ischemic stroke or systemic embolism through 3 years, tested for noninferiority. The following secondary endpoints will be tested if the primary endpoints are met: (1) all-bleeding, tested for noninferiority; (2) followed by testing for superiority; (3) disabling or fatal strokes, tested for superiority; all through 2 years.

Conclusions: CATALYST is evaluating the safety and effectiveness of a dual seal LAAO device compared to NOACs in patients with AF at increased risk of stroke.

Clinical trial registration: URL https://clinicaltrials.gov; Unique Identifier NCT04226547.

Aim: This study aims to use routinely collected health data and trial emulation methodology to inform the design of a pragmatic randomised controlled trial (RCT) in people requiring multivessel coronary revascularisation with severe symptomatic multivessel disease and high-risk characteristics, typically underrepresented in previous RCTs.

Methods: Hospital Episode Statistics (HES) linked to Office for National Statistics will be the main data source. The study population is patients who require multivessel myocardial revascularisation with at least one of the following high-risk characteristics: age >75 years, female, diagnosed with acute coronary syndrome, heart failure, chronic kidney disease, peripheral vascular disease, or intermediate frailty risk. The intervention procedure is coronary artery bypass grafting (CABG) and the control (reference) is percutaneous coronary intervention (PCI). Outcomes include all-cause and cardiovascular (CV) death, CV hospitalisation, major adverse cardiovascular events, and major vascular complications or bleeding within 5 years of the index procedure. This study includes three stages of statistical analyses: (1) latent class analysis (LCA) to identify mutually exclusive patient clusters (latent classes) representing different clinical phenotypes, (2) instrumental variable analysis (IVA) to estimate the average treatment effect (ATE) in the whole population and each patient cluster; and (3) repeating stage 2 in an emulated trial population obtained by matching the HES population with individual participant data from an RCT. We will then co-design the protocol for a definitive clinical trial in partnership with patients, public, and stakeholders.

Discussion: This study introduces a novel, stepwise data science framework that integrates machine learning (unsupervised learning through LCA), causal inference, and trial emulation methods applied in big data, to design a future stratified and adaptive RCT of CABG versus PCI in high-risk patients. Our proposed approach fosters new collaborations among data scientists, trial methodologists, clinicians, and patient and public representatives in complex trial designs for diverse, high-risk populations. This study represents a new framework for co-production in trials of cardiovascular interventions, which offers a scalable model and has the potential to transfer to other disease areas.

Trial registration: ClinicalTrials.gov (NCT05853536).

Background: Whereas reperfusion benefit in ST-elevation myocardial infarction (STEMI) is time-dependent, outcome data from very early primary percutaneous coronary intervention (PPCI) are limited. The STREAM-1 and -2 trials provided a unique opportunity to assess this issue. We evaluated electrocardiographic (ECG), angiographic, and clinical outcomes of early presenting STEMI patients undergoing PPCI, focusing on those treated <60 minutes of randomization.

Methods: We analyzed STEMI patients from STREAM-1 (n=1892) and STREAM-2 (n=604) trials presenting <3 hours of symptom onset who underwent PPCI. Endpoints included ECG (ST segment resolution, Q waves), angiographic (TIMI flow grade), 30-day composite of all-cause death, shock, heart failure, reinfarction, safety outcomes, and 1-year mortality.

Results: Patients undergoing PPCI <60 minutes of randomization (29.2%) were younger, more frequently male, and had shorter total ischemic times than those undergoing PPCI >60 minutes. ST resolution and TIMI flow outcomes were similar, but significantly fewer patients in the rapid PPCI group had Q waves on discharge ECG (58.2 vs. 71.9%, P <0.001). The 30-day composite outcome was lower in the <60 minutes group (10.1 versus 14.8%, RR 0.68 (95% CI 0.47-0.98) P=0.04), associated with a significant 62% reduction in cardiogenic shock (P=0.0008), and also had lower 1-year mortality (4.0 versus 7.2%; RR 0.56 (0.31-1.01), P(logrank)=0.047. After inverse probability weighted adjustment, the 30-day composite outcome and cardiogenic shock were RR 0.74 (0.50-1.08), P=0.116 and RR 0.45 (0.22-0.91), P=0.027, respectively, and the 1 year mortality was RR 0.70 (0.39-1.26), P=0.235. Safety endpoints were similar in both groups.

Conclusions: Substantial opportunity exists to improve outcomes for early-presenting STEMI patients undergoing PPCI. Establishing a first medical contact-to-PPCI time of <60 minutes provides incremental benefit.

Clinicaltrials: gov registration numbers: NCT00623623 (https://clinicaltrials.gov/study/NCT00623623), NCT02777580 (https://clinicaltrials.gov/study/NCT02777580).

Background: Transcatheter edge-to-edge repair (TEER) has emerged as an important therapy for severe mitral regurgitation. Current guidelines lack evidence-based recommendations for optimal postprocedural antithrombotic strategies, leading to heterogeneous clinical practices. And there are no randomized controlled trials (RCTs) available to compare different antithrombotic strategies following TEER.

Methods: STAR-TEER trial is an investigator-initiated, multicenter, randomized, parallel controlled, open-label trial, aiming to assess the safety and efficacy of de-escalated antithrombotic strategies with monotherapy in post-TEER patients with or without indications for oral anticoagulation (OAC) respectively. This trial plans to enroll 1,912 patients stratified into two cohorts: patients in Cohort A (requiring long-term OAC, n = 880) will be randomized 1:1 to rivaroxaban monotherapy or rivaroxaban plus clopidogrel, and patients in Cohort B (no OAC indication, n = 1,032) will be randomized 1:1 to aspirin monotherapy or aspirin plus clopidogrel. The primary outcome is all bleeding complications within 12 months post-TEER. The two key secondary outcomes are non-procedure-related bleeding within 12 months post-TEER (key secondary outcome 1) and a composite of ischemic events including all-cause mortality, stroke, systemic embolism, and myocardial infarction within 12 months post-TEER (key secondary outcome 2). A hierarchical hypothesis testing will be performed, with the primary outcome and key secondary outcome 1 tested for superiority, followed by the key secondary outcome 2 tested for noninferiority.

Conclusion: The STAR-TEER trial is the first large RCT to stratify patients based on OAC indication and compare different antithrombotic strategies following TEER in these two distinct cohorts.

Background: Elevated atherogenic lipoproteins increase risk of atherosclerotic cardiovascular disease (ASCVD), though long-term risk for adults without ASCVD who have low-normal levels has not been well described.

Methods: This study used pooled data from 16,384 individuals in three population-based prospective cohorts. At baseline all participants were without ASCVD and were not taking lipid-lowering therapy. We evaluated ASCVD events by baseline LDL-C, non-HDL-C and apoB, including low-normal values. ASCVD risk was assessed using multivariable Cox proportional hazards.

Results: The study cohort had a mean age of 52 (SD 18) years with 56.5% women, 64.7% of White race and 35.3% of Black race. Over a median follow-up of 18.8 years, unadjusted ASCVD event incidence was similar for adults with baseline LDL-C <70 mg/dL and 70-99 mg/dL, and higher with LDL-C ≥100 mg/dL; trends were similar for non-HDL-C and apoB categories. Compared to having baseline LDL-C 70-99 mg/dL, LDL-C <70 mg/dL was associated with similar ASCVD risk (adjusted HR 1.16 [95% CI 0.90-1.50]) and LDL-C ≥130 mg/dL was associated with higher risk (adjusted HR 1.31 [95% CI 1.14-1.50]) after multivariable adjustment; adults with non-HDL-C ≥160 mg/dL or apoB ≥90 mg/dL also had higher risk after multivariable adjustment.

Conclusions: Among adults without ASCVD not taking lipid-lowering therapy at baseline, ASCVD risk for adults with low-normal and high-normal LDL-C, non-HDL-C and apoB was similar, and their risk remained less than in adults with elevated lipoproteins. These findings emphasize the importance of achieving normal atherogenic lipoprotein levels for primary prevention of ASCVD from early adulthood through middle age.