BACKGROUND:Contemporary guidelines by the European Society for Cardiology and American College of Cardiology/American Heart Association for the treatment of non-acute myocardial ischaemic syndromes dispute the value of revascularisation and differ in their recommendation to perform revascularisation. A Bayesian network meta-analysis was performed, evaluating the strength of evidence for the comparative incremental effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) over medical therapy on long-term outcomes. METHODS:A hierarchical Bayesian network meta-analysis was designed (PROSPERO CRD42024541215, date 20 May 2024), including randomised controlled trials (RCTs) published between 2005 and 10 June 2025, which consisted of three initial treatment modalities: optimal medical therapy (OMT), PCI+OMT and CABG+OMT. The primary outcome was all-cause mortality at maximum follow-up; secondary outcomes were trates of the rates of myocardial infarction, stroke and re-revascularisation at maximum follow-up, expressed in HRs and 95% credible intervals (CrIs), accompanied by surface under the cumulative ranking curve (SUCRA) scores. RESULTS:10 RCTs, comprising 10 742 patients, were included. For all-cause mortality, the estimated median HR of CABG+OMT versus OMT was 0.84 (95% CrI 0.68-1.07); the HR of PCI+OMT versus OMT was 0.93 (0.79-1.16); and the HR of CABG+OMT versus PCI+OMT was 0.91 (0.71-1.13). The SUCRAs of a CABG+OMT strategy ranking as the optimal revascularisation treatment regarding mortality, myocardial infarction, stroke and re-revascularisation were 88.1%, 99.7%, 17.5% and 99.5%, respectively. Results were consistent across sensitivity analyses, including in the node-splitting models. CONCLUSIONS:This Bayesian network meta-analysis found that an initial CABG (+OMT) revascularisation strategy was associated with higher probabilities of optimal outcomes, with the exception of stroke, compared with an initial PCI (+OMT) revascularisation strategy, although CrIs overlapped, suggesting that some uncertainty remains. PROSPERO REGISTRATION NUMBER:CRD42024541215.

BACKGROUND:In ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), an invasive strategy demonstrated better health status outcomes than a conservative strategy in patients with chronic coronary disease (CCD). Some previous studies have shown greater health status benefits with coronary artery bypass grafting (CABG) than percutaneous coronary intervention (PCI). Whether the health status benefits of invasive management in ISCHEMIA were driven primarily by participants treated with CABG is unknown. METHODS:The aim of this analysis was to describe the health status outcomes of participants treated with a conservative strategy (n=2232) compared with invasively managed participants treated with PCI (n=1198) or CABG (n=340) in ISCHEMIA. The Seattle Angina Questionnaire-7 summary score (SAQ-SS) and angina frequency score (SAQ-AF) were the primary outcomes, with higher scores indicating better health status. Proportional odds models comparing 1- and 3-year outcomes were fit, adjusting for demographic, clinical, and angiographic characteristics. RESULTS:SAQ-SS in the conservative, PCI, and CABG groups increased by 9.9±18.1, 15.7±19.3, and 16.1±19.1 points at 1 year and 11.5±20.2, 16.5±21.8, and 15.0±19.4 points at 3 years, respectively. Freedom from angina in the conservative, PCI, and CABG groups was noted in 61.4%, 73.3%, and 82.4% at 1 year and 70.4%, 76.1%, 81.4% at 3 years, respectively. In risk-adjusted analyses, PCI and CABG were each associated with a higher SAQ-SS and SAQ-AF at 1 and 3 years compared with conservative management. SAQ-AF was higher with CABG than PCI at 1 year (odds ratio, 1.54 [95% CI, 1.03, 2.31]), but no differences between CABG and PCI were observed in SAQ-SS (odds ratio, 1.11 [95% CI, 0.78, 1.57]) or SAQ-AF (odds ratio, 0.94 [95% CI, 0.58, 1.54]) at 3 years. CONCLUSIONS:In ISCHEMIA, both PCI and CABG were associated with better 3-year health status than conservative management. Better angina relief with CABG than PCI was seen at 1, but not 3, years. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Graphical AbstractSummary of the top 10 papers in 2024 in ischaemic heart disease. AI, artificial intelligence; AI-QCT, atherosclerosis imaging–quantitative computed tomography; ANOCA, angina with non-obstructed coronary arteries; EF, ejection fraction; FAI, fat attenuation index; FFR, fractional flow reserve; HF, heart failure; LRP, lipid-rich plaque; MACE, major adverse cardiovascular events; MLA, minimal lumen area; PB, plaque burden; PCI, percutaneous coronary intervention; QoL, quality of life; TCFA, thin cap fibroatheroma.Open in new tabDownload slide

BACKGROUND:Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain. OBJECTIVES:This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes. METHODS:This was an observational study of participants with CCD in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. The primary outcome was cardiovascular (CV) death or myocardial infarction (MI). GDMT goals were systolic blood pressure (SBP) <130 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, not smoking, and antiplatelet therapy. Frequency of GDMT goals met at baseline and during follow-up is described. Bayesian joint modeling for longitudinal goal status and time-to-event analyses characterized the relative importance of specific GDMT goal attainment and timing with CV death/MI. RESULTS:All 5,179 ISCHEMIA participants were included. Among 4,914 participants with complete data on all 4 GDMT goals at baseline, 386 (9%), 2,073 (42%), 1,843 (38%), and 612 (12%) met 0-1, 2, 3, and 4 GDMT goals, respectively. The 4-year cumulative event rate for CV death/MI was highest for participants who attained no GDMT goals (24.5%; 95% credible interval [CrI]: 13.5%-42.2%) and lowest for those who attained all goals at baseline and remained at goal during follow-up (8.7%; 95% CrI: 6.7%-10.9%). SBP goal attainment was associated with a significant absolute event reduction in CV death/MI (-5.1%; 95% CrI: -11.3% to -1.0%), followed by antiplatelet therapy (-11.2%; 95% CrI: -29.1% to 0.8%), achieving low-density lipoprotein cholesterol <70 mg/dL (-2.0%; 95% CrI: -6.0% to 2.4%), and not smoking (-1.7%; 95% CrI: -9.3% to 4.2%). Ten millimeters of mercury lower SBP during follow-up was associated with 10% relative risk reduction of CV death/MI (RR [relative risk] = 0.90; 95% CrI: 0.82-0.98), after adjusting for other GDMT goals and baseline characteristics. CONCLUSIONS:Among participants with CCD, early attainment and maintenance of GDMT goals, especially SBP, were associated with fewer cardiovascular events. Compared with no GDMT goals at target, having all 4 GDMT goals at target at baseline was associated with an absolute 16% fewer CV deaths and MIs. (ISCHEMIA [International Study of Comparative Health Effectiveness With Medical and Invasive Approaches]; NCT01471522).

Patients with stable coronary artery disease (CAD) involving ≥50% stenosis in the left main coronary artery almost invariably undergo revascularisation. However, there is lack of evidence from contemporary randomised controlled clinical trials (RCTs) supporting the superiority of this approach versus an initial strategy of intensive, multifaceted optimal medical therapy (OMT) directed at dyslipidaemic, hypertensive, thrombotic, metabolic and ischaemic targets. Current clinical practice guidelines still base their recommendations on small subsets of RCTs conducted in the 1970s and early 1980s. Given the lack of survival benefit among patients with stable, multi-vessel coronary artery disease who do versus those do not undergo routine revascularisation in the era of advanced OMT, the question arises whether the current treatment recommendations for left main disease are valid. This issue is of considerable importance; while significant left main disease is found in only 8-10% of diagnostic invasive angiography cases, it is a disease entity associated with a high risk of adverse clinical events and extensive resource use. This article discusses clinical trials data as well as challenges to address this question in the contemporary era. It highlights the complexities of trial planning and execution as it relates to both feasibility and equipoise, study design, choice of trial endpoints and duration of follow-up. The authors conclude there is a compelling need for an RCT to test the hypothesis that the current practice of routine revascularisation for all patients with LMD is superior to an initial strategy of multifaceted OMT with selective use of revascularisation.

Rhythm control strategies are a key component of atrial fibrillation (AF) therapy, with recent reports suggesting racial and ethnic disparities in their utilization. We aimed to determine differences in the utilization of catheter ablation (CA), direct current cardioversion (DCCV), and anti-arrhythmic drugs (AAD) among different racial and ethnic groups. We searched PubMed/MEDLINE, EMBASE, and Cochrane Library (from inception to January 31st, 2024) for studies including adults with AF and reporting CA, DCCV, or AAD utilization rates in at least 2 racial and ethnic groups. Our primary outcome was the likelihood of Black, Hispanic, and Asian individuals undergoing each rhythm control strategy compared to White patients. Pooled estimates were calculated with a random-effects model and were reported as odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Nineteen studies were included comprising 12,598,109 patients. The pooled ORs (95% CI) of undergoing CA for Black individuals was 0.68 (95% CI 0.56 to 0.83), for Hispanic individuals was 0.72 (95% CI 0.63 to 0.82), and for Asian individuals was 0.64 (95% CI 0.48 to 0.86), compared to White individuals. The likelihood of undergoing DCCV (OR [95% CI]) was lower in Black (0.69 [95% CI 0.57 to 0.82]), Hispanic (0.67 [95% CI 0.57 to 0.80]), Asian (0.68 [95% CI 0.64 to 0.72]) patients compared to White patients. Our results identified that racial and ethnic minoritized groups with AF are significantly less likely to undergo treatment with a rhythm control strategy. In conclusion, these findings highlight a significant gap in healthcare delivery that stakeholders, healthcare systems, and clinicians should address.

BACKGROUND:In the ISCHEMIA Trial, 5,179 patients with stable coronary disease were randomized to initial invasive or conservative management. METHODS:PCI was recommended with a SYNTAX score 0 to 22 (low) and CABG with a SYNTAX score ≥33 (high). Either could be recommended for intermediate scores. The composite primary outcome was cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. There were 2 cohorts in this analysis. The descriptive cohort included patients who underwent CABG or PCI within 180 days of randomization and had no primary outcome before revascularization. The comparative cohort excluded patients with prior CABG, single vessel disease, SYNTAX score ≥ 45, and without core laboratory assessment. We focused on the intermediate (23-32) SYNTAX comparative group for which either CABG or PCI could be recommended. RESULTS:For 1,935 patients in the descriptive cohort (485 CABG, 1,450 PCI), the SYNTAX score was 27.3 ± 11.0 in the CABG group and 15.3 ± 8.6 in the PCI group, P < .0001. Most patients with low SYNTAX scores underwent PCI (87.1%), while most with high SYNTAX scores underwent CABG (72.6%). For the 1,203 patients (385 CABG, 818 PCI) in the comparative cohort, the adjusted 4-year primary event rate was 14.5% for CABG and 13.2% for PCI (difference 1.3%, 95% CI, -4.9% to 7.7%). For the 346 patients (163 CABG, 183 PCI) in the intermediate SYNTAX group, the adjusted 4-year primary event rate was 10.6% for CABG and 18.3% for PCI (difference -7.6%, 95% CI, -16.1% to 0.9%). CONCLUSIONS:Selection of revascularization method resulted in more PCI in the low SYNTAX group and more CABG in the high SYNTAX group. There was no statistical evidence of a difference between PCI and CABG in the intermediate SYNTAX group but the CIs are broad, reflecting uncertainty. CLINICAL TRIALS: GOV IDENTIFIER:NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.

OBJECTIVE:Indications for TAVI have been widened, although long-term device efficacy is still unclear. We aimed to compare the effectiveness of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) on a composite of death from any cause or stroke at 5-year follow-up according to risk profiles. METHODS:We performed a systematic literature review for randomized control trials (RCTs) comparing TAVI or SAVR. The primary endpoint was the composite of all-cause mortality or stroke at follow-up. Hazard ratios (HRs) and restricted mean survival time (RMST) differences within high, intermediate and low-risk profiles were estimated by reconstructing time-to-event data from these Kaplan-Meier curves. RESULTS:Eight trials were included (9811 participants). The incidence of composite endpoint increased concordantly with higher baseline risk profiles for both treatments. A time-variant effect was present with transcatheter superior to surgery early, as supported by a cumulative additional time-to-event of 0.77 months at 4 years driven by the high-risk group that is attenuated at 60 months. The benefit of the transcatheter approach increased over time up to 5 years in high-risk patients (RMST difference = 2.39; 95 %CI = -0.23;5.02; p-value = 0.07), while the benefit of the transcatheter approach in intermediate and low-risk patients showed a quadratic association with a smaller increase and attenuation of the observed benefit after 60 months postintervention (low-risk = 0.86; 95 %CI = -0.11,1.84; p-value 0.09; intermediate = 0.45; 95 %CI = -0.66;1.56; p-value = 0.42). CONCLUSIONS:Although an initial benefit of TAVI over SAVR, there are no significant differences at 5 years follow-up independently from the risk profile.

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

The optimal management of chronic coronary syndrome (CCS) patients has been a source of debate for several decades. Herein, we describe the evidence base comprising several landmark clinical trials including the most recent ISCHEMIA Trial, which, in aggregate, does not demonstrate a conclusive, incremental benefit of revascularization combined with optimal medical therapy (OMT) versus OMT alone in reducing prognostically-important clinical outcomes during long-term follow-up. For CCS patients with symptoms or quality of life not deemed refractory or unacceptable on medical therapy, a conservative approach to the judicious and selective use of revascularization plus OMT remains a justifiable evidence-based management strategy.

AIMS:Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIEDs) are increasingly recognized. However, uncertainty remains as to whether the risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared with cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). The study aims to synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS AND RESULTS:We searched PubMed, EMBASE, and Cochrane Library databases published until 31 October 2023. Significant post-CIED TR and MR were defined as ≥ moderate. Fifty-seven TR studies (n = 13 723 patients) and 90 MR studies (n = 14 387 patients) were included. For all CIED, the risk of post-CIED TR increased [pooled odds ratio (OR) = 2.46 and 95% CI = 1.88-3.22], while the risk of post-CIED MR reduced (OR = 0.74, 95% CI = 0.58-0.94) after 12 and 6 months of median follow-up, respectively. Right ventricular pacing via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR = 4.54, 95% CI = 3.14-6.57) and post-CIED MR (OR = 2.24, 95% CI = 1.18-4.26). Binarily, CSP did not alter TR risk (OR = 0.37, 95% CI = 0.13-1.02), but significantly reduced MR (OR = 0.15, 95% CI = 0.03-0.62). Cardiac resynchronization therapy did not significantly change TR risk (OR = 1.09, 95% CI = 0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR = 0.49, 95% CI = 0.40-0.61). There was no significant association of LP with post-CIED TR (OR = 1.15, 95% CI = 0.83-1.59) or MR (OR = 1.31, 95% CI = 0.72-2.39). Cardiac implantable electronic device-associated TR was independently predictive of all-cause mortality [pooled hazard ratio (HR) = 1.64, 95% CI = 1.40-1.90] after median of 53 months. Mitral regurgitation persisting post-CRT independently predicted all-cause mortality (HR = 2.00, 95% CI = 1.57-2.55) after 38 months. CONCLUSION:Our findings suggest that, when possible, adoption of pacing strategies that avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Background In 3146 REDUCE‐IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow‐up. Methods and Results We used participant‐level data from REDUCE‐IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in‐trial analysis was participant‐level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost‐effectiveness ratio (incremental costs divided by incremental quality‐adjusted life‐years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality‐adjusted life‐years with IPE compared with SC using in‐trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in‐trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost‐effectiveness ratio <$50 000 per quality‐adjusted life‐year gained. At a medication cost of $11.48 per day, the cost per quality‐adjusted life‐year gained was $36 208 in trial and $4135 over the lifetime. Conclusions In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost‐effective at $11.48 per day for conventional willingness‐to‐pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE‐IT USA. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Graphical AbstractOpen in new tabDownload slideThis figure summarizes the key messages in each of the 10 papers selected by the European Heart Journal Editors (ischaemic heart disease section). The three main areas discussed in this viewpoint article include: microvascular dysfunction, role of revascularization for management of obstructive coronary artery disease, and management of patients with acute coronary syndrome and clinical outcomes. ACS, acute coronary syndrome; CAD, coronary artery disease; CABG, coronary artery bypass grafting; CFR, coronary flow reserve; CMD, coronary microvascular dysfunction; LMCA, left main coronary artery; LV, left ventricle; MI, myocardial infarction; MRR, microvascular resistance reserve; OMT, optimal medical therapy; ORBITA-2, objective randomized blinded investigation with optimal medical therapy of angioplasty in stable angina; PCI, percutaneous coronary intervention.

Background Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. Methods and Results The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P=0.49), with no significant sex‐by‐treatment‐group interactions. Conclusions Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial. Registration URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.

Background: Cross-sectional Seattle Angina Questionnaire (SAQ) scores not only measure patients’ symptoms, function and quality of life, but are also associated with prognosis in chronic coronary disease (CCD). Yet, the prognostic significance of serial SAQ scores in the modern era is unknown, particularly after revascularization. Hypothesis: Serial collection of SAQ scores can provide updatable estimates of clinical risk in patients with CCD. Aims: To describe the association of serial SAQ Summary Scores (SAQ-SS) with the primary endpoint of the ISCHEMIA trial (CV death, MI, or hospitalization for heart failure, unstable angina, or resuscitated cardiac arrest), stratified by medical management and recent revascularization. Methods: Analyses were framed from the perspective of a clinician reviewing the SAQ-SS in clinic and seeking to understand whether the prior score, the current score, or the change was most prognostic of subsequent clinical events. Cox models were created using the 3-month, 6-month, and change between the 3- and 6-month SAQ-SS scores, individually, as well as those scores in combination to find the most prognostic permutation. Each model was adjusted for 17 potentially confounding covariates. We performed separate analyses for the conservative and invasive management cohorts. In the conservative group, we excluded those who underwent revascularization prior to their 6-month assessment. In the invasive group, we included only patients who were revascularized within the first three months. In both groups, we excluded patients with events prior to 6 months. Results: In both the conservatively managed (n=1965) and recent revascularization (n=1447) cohorts, unadjusted analyses estimated a 6-9% lower risk of clinical events over a median of 3.2 years for each 5-point increase in SAQ-SS score. The current SAQ-SS score was most strongly associated with clinical events, even after including the prior SAQ-SS score and all other covariates (Table). Conclusions: Routine clinical use of the SAQ provides an updatable measure of risk in patients with CCD—managed either medically or with revascularization—with the current SAQ-SS score demonstrating the strongest association with clinical events.

Background: Artificial-intelligence-enabled analysis of atherosclerotic plaque characteristics on coronary computed tomography angiography (CCTA) may improve sex-specific risk prediction of cardiovascular (CV) events. Aims: The aim of this study was to examine sex differences in CCTA-derived atherosclerotic plaque analysis in ISCHEMIA participants, and to identify any interaction between sex and the prognostic value of quantitative atherosclerosis parameters in predicting CV events. Methods: In a post-hoc analysis, atherosclerosis imaging quantitative CT (QCT) was performed on all available CCTA scans. Interaction analysis was performed to understand the impact of female sex on the relationship between QCT variables and the outcomes of CV death or myocardial infarction (MI), all-cause death, and MI alone over a median follow-up of 3.3 years. Results: Of the 3645 participants with CCTA available for analysis, mean age was 64 and 21% were female. Females had lower total, calcified, non-calcified, and low-density non-calcified plaque volume than males (p<0.001 for all, Table). Percent atheroma volume (PAV=total plaque volume /vessel volume x 100%) was associated with CV death or MI in all participants, and the association was stronger in females (univariate HR: 2.37, 95% confidence interval (CI) 1.79, 3.14, p<0.001) than men (HR: 1.70, 95% CI 1.45, 2.00, p<0.001). There was a significant interaction showing accentuated risk of CV death or MI associated with greater PAV among females vs. males (HR for female*PAV: 1.42, 95% CI 1.03, 1.95, p=0.032, Figure), mainly driven by risk for MI. Conclusions: In ISCHEMIA, females presenting with moderate or severe ischemia and obstructive CAD had less atherosclerotic plaque burden of all subtypes and less adverse plaque characteristics identified by CCTA than men. The risk associated with greater atherosclerotic burden (PAV) was higher among female participants than males for the composite outcome of CV death or MI.