Over the past two decades, approaches to managing patients with coronary artery disease have improved substantially with advances in percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery, pharmacological secondary prevention, anti-anginal agents and lifestyle interventions. Accordingly, clinical management choices in non-acute myocardial ischaemic syndromes (NAMIS) remain a timely and important topic. The risks and benefits of an invasive strategy combined with optimal medical therapy (OMT) versus a conservative strategy of OMT alone should be discussed with patients to facilitate shared clinical decision making. The findings from high-quality, randomized, controlled trials in the era of modern OMT form an essential platform for these informed conversations. In totality, the evidence from randomized, controlled trials supports OMT as the first-line therapeutic approach in patients with NAMIS, whereas selected patients at high anatomical risk or those with persistent anginal symptoms despite initial OMT often derive further symptom relief from invasive therapy with PCI. In patients with high-risk NAMIS, including those with multivessel disease and diabetes mellitus, CABG surgery improves survival, whereas the benefit is less clear for PCI. In this Review, we discuss the findings from contemporary trials evaluating outcomes in patients with NAMIS treated invasively or conservatively with OMT alone, and we conclude with proposed management pathways.

BACKGROUND:The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS:The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS:Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS:In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION:ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

BACKGROUND:Studies comparing treatment strategies based on initiation timing-such as starting PCSK9 inhibitor (PCSK9i) therapy sooner versus later after a myocardial infarction (MI)-are prone to immortal time bias. Clone-censor-weight methods can address these issues and allow the researcher to emulate a trial in which patients are assigned to protocols dictating when PCSK9i is initiated. This study aimed to evaluate the comparability of patients in a clone-censor-weight setup who initiated a PCSK9i within 12 months post-MI versus non-initiators. METHODS:We included adult patients hospitalized for MI in Sweden (2015-2021) and followed them for 3 years. We considered two treatment strategies: initiating PCSK9i within 12 months versus not initiating PCSK9i during the same period. We applied the clone-censor-weight method to address immortal time bias and assessed remaining bias using covariate balance metrics and negative control outcomes. RESULTS:The primary study sample included 38  627 episodes of MI, with 561 (1.5%) initiating PCSK9i treatment within 12 months. These patients were younger, had higher baseline LDL-C levels, and were more frequently treated with ezetimibe during their post-MI follow-up compared to non-initiators. Although clone-censor-weight estimation was free of immortal time bias, it faced challenges in achieving adequate balance of covariates due to the high rates of censoring (relatively small number of people initiating a PCSK9i in the first year) and strong association between covariates and censoring. Truncation of weights provided more stable estimates but at the expense of some covariate imbalances. CONCLUSIONS:The clone-censor-weight method is a promising approach that allows researchers to answer questions about the effect of treatment policies. But practical guidance is needed to address problems that arise from small, highly imbalanced groups, which is common with most newly introduced treatments.

BACKGROUND:The ISCHEMIA trial randomized participants with chronic coronary disease and moderate or severe ischemia by site assessment to an initial invasive strategy plus guideline-directed medical therapy (GDMT) or to an initial conservative strategy of GDMT alone. This secondary analysis examines the association of pre-randomization ischemia severity, from stress testing assessed by a core laboratory, and anatomic severity of coronary artery disease (CAD), assessed by coronary computed tomography angiography (CCTA), with 1-year health status outcomes. METHODS:The associations of ischemia and CAD severity with 1-year health status were assessed using proportional odds models, adjusted for age, sex, and baseline health status and stratified by baseline angina; Seattle Angina Questionnaire (SAQ) Angina Frequency [AF] score < 100 (and angina) vs. 100 (no angina). RESULTS:Among 4,558 participants with baseline and 1-year SAQ assessments, 2936 (64.4%) had baseline angina. Among these, ischemia was categorized as no/mild (363), moderate (986) and severe (1587). Among participants reporting angina at baseline, those with severe baseline ischemia had more frequent angina compared with those having less ischemia (SAQ AF, 70.6 vs 73.0, p=0.029). However, the adjusted odds ratio for better 1-year overall health status, assessed by the SAQ Summary Score, was 1.29 (95% CI, CI 1.05-1.59, p=0.007) for participants with severe vs. those with less baseline ischemia. No differences in 1-year health status were observed by CAD severity or in asymptomatic patients categorized by ischemia or CAD severity. CONCLUSIONS:Among participants with baseline angina in the ISCHEMIA trial, severe ischemia was independently associated with more frequent angina at baseline and at 1 year, but also with better 1-year overall health status compared with less ischemia. Anatomic CAD severity was not associated with angina severity.

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.

Purpose The Zoī cohort is a prospective longitudinal cohort study, designed to advance personalised prevention by systematically screening for undiagnosed or asymptomatic conditions, identifying early risk markers and predicting future disease risks. Participants Recruitment takes place in a dedicated prevention-focused health centre. Adults aged 18 years and older are enrolled either as paying customers or through company-sponsored programmes. This manuscript presents the design of the cohort and the characteristics of the first 1000 participants (67.5% male, mean age 51.1 years, high education levels). The cohort exhibits a healthy volunteer bias, with lower smoking and obesity rates and higher educational attainment than the general French population, which limits generalisability. Findings to date Data collection is conducted in a standardised environment and combines over 500 self-reported items, clinical examinations, extensive biomarker profiling (196 biomarkers) and multimodal imaging (vascular, breast, abdominal and pelvic ultrasound, full-body composition, retinal scan). For several major diseases, risk is further estimated through established clinical prediction models. Despite lower obesity and smoking rates than the general population, almost half (45.6%) of those who reported no ongoing diseases had at least one undiagnosed chronic condition, most frequently hypertension and hypercholesterolaemia. Male sex and older age were significantly associated with disease unawareness (p<0.05). These findings highlight a discrepancy between self-reported and objectively measured health status, even in a health-conscious population. Future plans Longitudinal follow-up is collected via yearly re-evaluations and through a dedicated application. The cohort is designed as a deeply phenotyped, longitudinal resource to support interdisciplinary research collaborations, the development and validation of early risk stratification models and the evaluation of preventive interventions.

BACKGROUND AND AIMS:Sex differences in the longitudinal evolution of low-density lipoprotein cholesterol (LDL-C) management among patients with chronic coronary syndromes (CCS) are not well known. METHODS:In the international CLARIFY registry, which included patients with CCS, LDL-C levels were monitored annually over the 5-year follow-up period. The analysis included patients with available LDL-C measurement at baseline. Target LDL-C was set at 100 mg/dL, in line with prevailing recommendations at enrolment. Sex-specific differences in LDL-C were adjusted for age and geographical region. Impact of longitudinal LDL-C was assessed using mean LDL-C up to the primary outcome of interest or last follow-up defined as cardiovascular (CV) death or MI during 5-year follow-up, evaluated using multivariable analysis. RESULTS:Of 32,376 patients in the initial cohort, women were less likely to have LDL-C measurement available at baseline (aOR 1.12, 95%CI 1.06-1.18, p<0.001). Of the 21,925 patients with LDL-C measurement at baseline, 21.6% were women. At inclusion, women were less likely to receive statins (82.7% vs. 85.4%, p<0.001) and more likely to fail reaching the LDL-C target (45.6% vs. 37.4%; aOR 1.47, 95%CI 1.38-1.58, p<0.001). This disparity persisted across the 5-year follow-up (p<0.001 for every year). Overall, women were more likely than men to never reach the target LDL-C during follow-up (20.7% vs. 15.8%; aOR 1.44, 95% CI 1.32-1.56, p<0.001). Higher mean LDL-C during follow-up was associated with an increased risk of the primary outcome (aHR 1.06 per 10 mg/dL increase, 95% CI 1.04-1.07, p<0.001). CONCLUSION:Women with CCS were less likely to have LDL-C measurement available at baseline, to receive lipid-lowering drugs and consistently exhibited poorer LDL-C control than men over the 5-year follow-up. Given the association of LDL-C and adverse CV outcomes, targeted interventions to close the sex gap in secondary prevention are needed.

BACKGROUND AND AIMS:After acute coronary syndrome (ACS), high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels have been associated with risk of major adverse cardiovascular events (MACE). Whether the prognostic information provided by hsCRP and IL-6 is independent and complementary after ACS is unclear. METHODS:The ODYSSEY OUTCOMES trial compared alirocumab with placebo in post-ACS patients on optimized statin therapy. In post hoc analyses, the relation between log-transformed hsCRP and IL-6 levels and risk of MACE and all-cause death was assessed in proportional hazards models. RESULTS:A total of 11 817 patients had baseline hsCRP and IL-6 data; 1306 had a MACE primary endpoint and 458 died. Median hsCRP, IL-6, and low-density lipoprotein cholesterol (LDL-C) were 1.54 mg/L, 5.00 pg/ml, and 86 mg/dl, respectively. hsCRP and IL-6 had moderate correlation (r = 0.52). In models for one biomarker adjusted for the other biomarker, treatment assignment, age, sex, diabetes, LDL-C, and time since index ACS, hsCRP was a significant independent predictor of MACE (P < .0001) and IL-6 was not (P = .21); both independently predicted death (P < .0001 for hsCRP and P = .0003 for IL-6). Relationships did not depend on treatment (all Pinteraction > .25). When dichotomized at 2 mg/L (hsCRP) and 5 pg/ml (IL-6), risks of MACE and death were significantly elevated when both, but not when one marker was elevated. CONCLUSIONS:In patients with recent ACS, hsCRP independently predicted MACE, while both hsCRP and IL-6 predicted death. Together, the two markers provided complementary prognostic information. hsCRP conveys independent information on inflammatory risk beyond that provided by IL-6.

Importance:Anterior acute myocardial infarction is associated with increased risk of left ventricular (LV) thrombus. The benefit and risk of adding an oral anticoagulant to dual antiplatelet therapy (DAPT) in preventing LV thrombus remain uncertain. Objective:To determine whether the addition of low-dose rivaroxaban to DAPT reduces the incidence of LV thrombus at 1 month in patients with anterior ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants:This multicenter, open-label, blinded-end point randomized clinical trial was performed in 29 centers in France. The trial was nested in the ongoing FRENCHIE (French Cohort of Myocardial Infarction Evaluation) registry. Between October 2021 and January 2023, patients with anterior STEMI were enrolled. The last date of participant follow-up was in March 2023. Data analysis was performed from September 2024 to July 2025. Interventions:Patients were randomized to receive either DAPT plus rivaroxaban, 2.5 mg, twice daily for 4 weeks (n = 283) or DAPT alone (aspirin ≤100 mg per day and either clopidogrel, 75 mg per day, or ticagrelor, 90 mg twice a day [n = 277]), as soon as possible following completion of the initial percutaneous coronary intervention or angiography procedure. Main Outcomes and Measures:The primary end point was presence of LV thrombus on contrast-enhanced cardiac magnetic resonance imaging at 1 month. Results:Among 560 patients with anterior STEMI enrolled (mean [SD] age, 61.1 [11.6] years; 121 female patients [21.6%]), LV thrombus was detected in 38 patients (13.7%) receiving rivaroxaban and 47 patients (16.6%) with DAPT alone (difference, -2.9%; 95% CI, -8.9% to 3.2%; P = .34). No difference was observed between the 2 groups regarding the largest diameter of LV thrombus or the incidence of major adverse cardiovascular events. The incidence of major bleeding events (Bleeding Academic Research Consortium [BARC] ≥type 2) was also comparable (4 [1.5%] with DAPT plus rivaroxaban vs 2 [0.7%] with DAPT alone; difference, 0.7%; 95% CI, -1.3% to 3.1%), whereas minor bleeding events (BARC type 1) occurred more frequently in the DAPT plus rivaroxaban group (45 [16.4%] vs 20 [7.2%]; difference, 9.3%; 95% CI, 3.6%-14.8%). Conclusions and Relevance:In this multicenter randomized clinical trial among patients with anterior STEMI, the addition of low-dose rivaroxaban to DAPT did not demonstrate a statistically significant reduction in LV thrombus formation at 1 month but did increase minor bleeding. Given the limited power of the study, these findings should be interpreted with caution, as a modest effect cannot be excluded. Trial Registration:ClinicalTrials.gov Identifier: NCT05077683.

OBJECTIVE:Sotagliflozin, a dual sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor, improves kidney and heart failure (HF) outcomes through incompletely understood mechanisms. Soluble urokinase plasminogen activator receptor (suPAR), an immune-derived glycoprotein, is implicated in kidney and cardiovascular disease pathogenesis. We investigated whether sotagliflozin reduces suPAR levels; whether baseline suPAR predicts cardiovascular outcomes; and whether baseline suPAR modifies sotagliflozin's treatment effect. RESEARCH DESIGN AND METHODS:We measured suPAR levels at baseline and at 1-year follow-up in a subset of patients from the SOLOIST-WHF (Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening HF) trial, which evaluated sotagliflozin's effect on the composite outcome of cardiovascular death, HF hospitalization, and urgent HF visits in patients with type 2 diabetes and worsening HF. Cox proportional hazards modeling assessed associations between baseline suPAR and outcomes and tested for treatment-by-suPAR interaction. Analysis of covariance (ANCOVA) compared changes in suPAR between treatment groups. RESULTS:In the main SOLOIST-WHF trial, sotagliflozin reduced the primary composite outcome (HR 0.67, 95% CI 0.52-0.85). In this ancillary analysis (n = 815 with available samples), the median baseline suPAR level was 4.7 ng/mL (IQR 3.7-6.1). SuPAR levels decreased similarly in both treatment groups at 1 year: sotagliflozin (n = 97, -6.2%, 95% CI [-12.0, -0.04]) vs placebo (n = 101, -7.9%, 95% CI [-13.5-2.0]; P = 0.69). Baseline suPAR was strongly associated with the primary outcome in a graded, dose-response manner, independent of treatment, systolic function, kidney function, and NT-proBNP levels: adjusted hazard ratio 2.21 (95% CI 1.36-3.60) for the fourth quartile (>6.06 ng/mL) vs the first quartile (≤3.67 ng/mL). The treatment effect of sotagliflozin was consistent across suPAR quartiles (P interaction = 0.90). CONCLUSIONS:The cardiovascular benefits of sotagliflozin are unlikely to be related to suPAR reduction, because sotagliflozin did not significantly alter suPAR levels, and treatment efficacy was consistent across suPAR strata. However, suPAR remains a strong, independent predictor of HF outcomes. Further studies are needed to determine whether suPAR-targeted therapies can improve HF outcomes.