OBJECTIVES:Recent randomized controlled trials (RCTs) challenge the routine practice of keeping patients NPO ("nil per os") after midnight before diagnostic cardiac catheterization. Shorter fasting durations improve patient experience without increasing risks; however, systematic uptake into routine practice remains limited. At a high-volume cardiac care centre, patients were still being required to fast from midnight, despite emerging evidence. To assess the feasibility of shifting long‑standing practice patterns, we established a >70% adherence target for uptake of a shortened fasting protocol. METHODS:A structured quality improvement initiative using sequential Plan-Do-Study-Act (PDSA) cycles modified pre-procedural fasting protocols to permit a light meal up to 2 hours before cardiac catheterization and clear fluids until the procedure (i.e., intervention). Patient experience surveys were administered to intervention and control groups in 2 PDSA cycles, followed by a post-implementation intervention group. The primary outcome was adherence to shortened fasting protocols (>70% target). Secondary outcomes included patient comfort, satisfaction, safety events, and sustained uptake. RESULTS:Cycle 1 included 97 outpatients (37 control, 60 intervention), cycle 2 included 84 inpatients (40 control, 44 intervention), and 45 patients were in the post-implementation group. Target adherence was met (77% in cycle 1, 82% in cycle 2, and 79% at post-implementation). Patients in the intervention groups reported lower hunger (cycle 1 outpatients) and lower nausea (cycle 2 inpatients), while satisfaction scores remained consistently high across all groups. No aspiration, intubation, or escalation to higher-level care was observed. CONCLUSIONS:Shortening fasting requirements to 2 hours before cardiac catheterization was feasible to implement in a high‑volume cardiac centre.

Background:Stent failure (SF) is a complication of percutaneous coronary intervention (PCI). Objectives:This study aimed to assess the relationship of the optical coherence tomography (OCT) determined cause of SF with time since stent implantation, treatment, and outcome. Methods:This retrospective study included patients who underwent an OCT evaluation for SF from January 2013 to July 2023. In-stent findings were evaluated on OCT including tissue proliferation, tissue type, underexpansion, thrombus, and multiple stent layers. The relationship between time to presentation, treatment, and outcome was assessed. Results:Of the 309 patients who underwent an OCT-guided PCI for SF, tissue proliferation was present in 228 (74%) and absent in 81 (26%). Among patients with tissue proliferation, OCT commonly showed lipidic neointima (n = 122, 54%), thrombus (n = 81, 36%), and underexpansion (n = 71, 31%). In patients without tissue proliferation, OCT commonly identified underexpansion (n = 58, 72%), thrombus (n = 55, 68%), and uncovered struts (n = 37, 46%). The mean time to SF was 6.89 ± 5.88 years with tissue proliferation and 2.98 ± 3.75 years without (p < 0.001). Patients with tissue proliferation were more likely to be treated with repeat stenting (78% vs. 60%, p < 0.001). Lipidic neointimal tissue and >1 layer of stent were predictors of target SF recurrence during a median 3 years of follow-up. Conclusion:In a large series of OCT-guided treatments of SF, tissue proliferation was more common, occurred later after stent implantation, and was more likely to be treated with repeat stenting than no-tissue proliferation. Lipidic neointimal tissue and >1 layer of stent were significant predictors of target SF during follow-up.

Optimal long term antithrombotic treatment in high-risk chronic coronary syndrome (CCS) patients remains uncertain. Both ticagrelor (60 mg BID) and low-dose rivaroxaban (2.5 mg BID) in addition to low-dose aspirin resulted in significant reductions in major cardiovascular events in high-risk patients at the expense of increased bleeding risk. We aimed to compare the effects of both strategies on bleeding time, fibrin clot lysis time and inflammatory biomarkers in CCS patients with history of acute coronary syndrome. Twenty aspirin-treated patients were recruited into a randomized crossover study to receive ticagrelor 60 mg BID in 1 week and rivaroxaban 2.5 mg BID in the other with a 2-week washout period in between. Outcome measures were determined at the start and end of each treatment week. Two-way ANOVA was used to determine difference in treatment effect. Data are presented as mean ± SD. At baseline, there was no significant difference in any studied outcome measure. Bleeding time was significantly longer with ticagrelor compared to rivaroxaban (Ticagrelor: 897 ± 481secs vs. Rivaroxaban: 440 ± 184 secs; p = .0001). Fibrin clot lysis time was not impacted by ticagrelor but significantly dropped post treatment with rivaroxaban (Ticagrelor: 5743 ± 2590 secs vs. Rivaroxaban: 4309 ± 2308 secs; p = .0049). Neither treatment had an impact on levels of high-sensitivity CRP or white cell count. In conclusion, ticagrelor 60 mg BID has greater impact on bleeding time compared to rivaroxaban 2.5 mg BID. Whereas rivaroxaban, positively modulates fibrin clots, rendering them more prone to lysis.

Aims:In the complete revascularization with multivessel PCI for myocardial infarction (COMPLETE) trial, staged complete revascularization in patients with ST-segment-elevation myocardial infarction (MI) reduced major adverse cardiovascular events compared with culprit-only revascularization. Inclusion was based on angiographic criteria. Objectives:We modelled non-culprit virtual fractional flow reserve (vFFR) and investigated interactions between physiological lesion severity and the benefits of complete revascularization in COMPLETE. Methods and results:All suitable angiograms from COMPLETE underwent software-based 3-dimensional (3D) arterial reconstruction and analysis of 3D-quantitative coronary angiography (QCA) and vFFR using computational fluid dynamics software. Physiological lesion significance was defined as vFFR ≤0.80 and was compared with operators' visual angiographic analysis, 2D-QCA and 3D-QCA. vFFR was computed in 635 patients (710 lesions). 302 patients (48%) had ≥1 physiologically significant lesion and 333 (52%) had none. 321 (45%) lesions were physiologically significant and 389 (55%) were not. There was no statistically significant interaction between physiological lesion significance and any of the trial co-primary or key secondary clinical outcomes, or an exploratory outcome of ischaemia-driven revascularization without preceding MI (all interaction P > 0.30). 3D-QCA predicted vFFR significance more accurately than visual and 2D-QCA (concordance 73% vs. 49% vs. 59%, respectively). Conclusion:In this virtual physiological substudy of the COMPLETE trial, 52% of patients lacked any physiologically significant lesions and the benefits of complete revascularization appeared to be independent of physiological lesion significance. 3D-QCA was a better predictor of physiological significance than either 2D-QCA or operator visual analysis. Further research is warranted to compare angiography-guided and physiology-guided complete revascularization strategies.

BACKGROUND:Female patients are at greater risk of adverse events following non-ST-elevation acute coronary syndrome but less frequently receive guideline-recommended coronary angiography and revascularization. Routine invasive management benefits high-risk patients, but evidence informing the optimal timing of angiography specifically in female patients is lacking. METHODS:Medline, Web of Science, and Scopus were searched up to November 2023. Randomized controlled trials investigating early versus delayed timing of coronary angiography in patients with non-ST-elevation acute coronary syndrome were included. Individual patient data from female patients were extracted. The primary end point was a composite of all-cause mortality or myocardial infarction at 6 months. We performed a 1-stage individual patient data meta-analysis using random-effects Cox models. RESULTS:Six trials contributed individual patient data from 2257 female patients. Median time to coronary angiography was 5 hours in the early invasive group (n=1141) and 49 hours in the delayed invasive group (n=1116). Overall, there was no significant reduction in the risk of the primary end point in the early invasive group compared with the delayed group (hazard ratio, 0.79 [95% CI, 0.60-1.06]; P=0.12). Early invasive management was associated with a reduction in recurrent ischemia (hazard ratio, 0.60 [95% CI, 0.39-0.94]; P=0.025). In the prespecified subgroup analysis, high-risk female patients with Global Registry of Acute Coronary Events score >140 receiving early invasive management experienced a significantly reduced hazard for all-cause mortality or myocardial infarction at 6 months (hazard ratio, 0.65 [95% CI, 0.45-0.94]; P=0.021; Pinteraction=0.035). Similar benefits were observed for female patients with elevated cardiac biomarkers. CONCLUSIONS:Early invasive management in female patients with non-ST-elevation acute coronary syndrome, compared with delayed invasive management, was not associated with a significant reduction in the hazard for the primary end point. In prespecified subgroup analysis, high-risk female patients as assessed with Global Registry of Acute Coronary Events score >140 or elevated cardiac biomarkers experienced significant reductions in all-cause mortality or myocardial infarction at 6 months following early invasive management. REGISTRATION:URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42023468604.

BACKGROUND: Short dual antiplatelet therapy (DAPT) followed by ticagrelor monotherapy may be a valuable therapeutic option for patients with chronic coronary syndrome (CCS) and high ischaemic risk (HIR) undergoing percutaneous coronary intervention (PCI). AIMS: We aimed to compare ticagrelor monotherapy with ticagrelor-based DAPT in CCS patients with and without HIR undergoing PCI. METHODS: The present analysis included the CCS cohort of the TWILIGHT trial, which randomised PCI patients to ticagrelor alone or in combination with aspirin for 12 months after 3 months of ticagrelor-based DAPT. Patients were stratified into HIR and non-HIR based on the 2019 European Society of Cardiology (ESC) CCS guidelines definition. Outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction or stroke, and Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding at 1 year. RESULTS: Of the 2,503 CCS patients who underwent randomisation, the ESC definition classified 1,264 (50.5%) as HIR and 1,239 (49.5%) as non-HIR. HIR patients displayed a higher risk of MACCE (3.9% vs 2.3%; p=0.015) and similar rates of BARC Type 2-5 bleeding (5.1% vs 5.7%; p=0.455) as compared to non-HIR patients. Ticagrelor monotherapy and ticagrelor-based DAPT were associated with similar risks of MACCE (HIR: 4.0% vs 3.8%, hazard ratio [HR] 1.06, 95% confidence interval [CI]: 0.60-1.85; non-HIR: 2.1% vs 2.6%, HR 0.80, 95% CI: 0.38-1.66, pinteraction=0.553) and bleeding (HIR: 4.7% vs 5.7%, HR 0.82, 95% CI: 0.50-1.33; non-HIR: 4.9% vs 6.7%, HR 0.71, 95% CI: 0.44-1.14; pinteraction=0.684) in both the HIR and non-HIR groups. CONCLUSIONS: In a post hoc analysis of the TWILIGHT trial that included CCS patients undergoing PCI, ticagrelor monotherapy after 3 months of DAPT appeared to be safe and was not associated with increased risks of ischaemic or bleeding events, regardless of baseline HIR status, compared with standard ticagrelor-based DAPT. These findings suggest the potential to expand guideline recommendations for ticagrelor monotherapy in CCS.

AIMS:In standard time-to-first event analysis, early aspirin discontinuation followed by ticagrelor monotherapy has been shown to reduce bleeding without increasing ischaemic complications compared with ticagrelor plus aspirin after percutaneous coronary intervention (PCI). We evaluated whether these treatment effects are preserved when recurrent events are considered. METHODS AND RESULTS:In this TWILIGHT trial post-hoc analysis, we assessed the effects of ticagrelor monotherapy on the total number of events that occurred over the 12-month follow-up among 7119 high-risk patients randomized to aspirin or placebo in addition to ticagrelor at 3 months post-PCI if event-free and adherent to treatment. There were 391 patients with at least one Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (primary endpoint). Of those, 28 (7.2%) had a recurrent event. The total number of BARC 2, 3, or 5 bleeding events was 148 in the ticagrelor monotherapy arm compared with 278 with ticagrelor plus aspirin arm (P < 0.001). Among 272 patients with at least one key secondary ischaemic endpoint (all-cause death, myocardial infarction, or stroke), 37 (13.6%) sustained a recurrent event. Total ischaemic events were similar (155 vs. 159) in the two groups. CONCLUSION:Among selected high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy followed by ticagrelor with or without aspirin, recurrent bleeding was less common than recurrent ischaemic events over 12 months. Analysis of total events indicates that ticagrelor monotherapy continues to be more effective than ticagrelor plus aspirin in reducing bleeding without a signal of ischaemic harm.

BACKGROUND Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P=0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization).

Background Despite current antiplatelet therapy, patients remain at risk of recurrent ischemic events after acute coronary syndromes (ACS), which may reflect persistently elevated thrombin generation. Factor XIa inhibition reduces thrombin generation and may improve clinical outcomes with minimal bleeding risk. Design Librexia ACS (ClinicalTrials.gov NCT05754957) is a Phase 3, randomized, double-blind, placebo-controlled, event-driven trial to test the efficacy and safety of milvexian, an oral, selective factor XIa inhibitor, in addition to conventional antiplatelet therapy after a recent ACS. Eligibility criteria include symptoms of spontaneous ischemia, a diagnosis of ACS and cardiac biomarker elevation indicative of myonecrosis within 7 days before randomization, along with at least 2 risk-enhancing factors. Participants are randomly assigned to oral milvexian (25 mg twice daily) or a matched placebo. Randomization is stratified according to the planned duration and type of antiplatelet therapy. The primary efficacy endpoint is the time to first occurrence of the composite of cardiovascular death, myocardial infarction (MI), or ischemic stroke that will enroll approximately 16,000 patients with follow-up until 875 events are accrued. The first major secondary endpoint is time to the first occurrence of cardiovascular death, MI, ischemic stroke, major adverse limb events, and symptomatic venous thromboembolism. The principal safety endpoint is Bleeding Academic Research Consortium 3c or 5 bleeding. Summary The Librexia-ACS trial will determine the efficacy and safety of milvexian after ACS and will be the first trial to test whether factor XIa inhibition in addition to standard-of-care antiplatelet therapy reduces major adverse cardiovascular events without an increased risk of significant bleeding.

Aims:Studies investigating the timing of coronary angiography in non-ST-elevation acute coronary syndrome (NSTE-ACS) have not evaluated sex differences. This study aims to investigate the sex-related differences in outcomes of NSTE-ACS patients undergoing early or delayed invasive management. Methods and results:An individual patient data (IPD) meta-analysis was performed after systematic review of randomized controlled trials (RCTs) comparing early vs. delayed invasive strategy among NSTE-ACS patients. The primary endpoint was a composite of all-cause death or myocardial infarction (MI) at 6 months. Secondary endpoints included all-cause death, MI, recurrent ischaemia, stroke, and major bleeding. One-stage, random-effects Cox models were conducted. This meta-analysis was registered with PROSPERO (CRD42023468604). Six RCTs including 6654 patients were identified, of whom 2257 (33.9%) were females with a median age of 69 years [interquartile range (IQR) 60-76], significantly higher than males (64.5 years, IQR 55-72.1, P < 0.001). Among patients undergoing early strategy, there was no sex difference in the occurrence of the primary [Hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.83-1.41, P = 0.560] and secondary endpoints. Among patients undergoing delayed strategy, there was no difference in the occurrence of the primary endpoint (HR 1.12, 95% CI 0.88-1.43, P = 0.350). Female sex undergoing delayed strategy was associated with higher risk of recurrent ischaemia (HR 1.52, 95% CI 1.06-2.19, P = 0.023) and major bleeding (HR 1.88, 95% CI 1.22-2.87, P = 0.004) using univariable analysis but not using multivariable analysis. Conclusion:No sex-related differences in the composite of all-cause death or MI were identified among NSTE-ACS patients undergoing early and delayed invasive management.

BACKGROUND Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P=0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P=0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure.

Therapeutic anticoagulation is essential to prevent and treat venous and arterial thromboembolism. The available agents target coagulation factors involved in thrombus formation but are associated with an increased risk of bleeding. Factor XI plays a minor role in haemostasis but contributes substantially to thrombus expansion, making it an attractive target to mitigate bleeding while maintaining antithrombotic efficacy. Various novel inhibitors, including antisense oligonucleotides, monoclonal antibodies and small molecules, have been developed. Phase II trials in orthopaedic surgery showed dose-dependent reductions in venous thromboembolism without significantly increasing bleeding compared with enoxaparin. In the first phase III trial of a small-molecule inhibitor of activated factor XI in patients with atrial fibrillation, asundexian was associated with a reduction in bleeding but also a higher risk of stroke, compared with apixaban. Factor XI inhibitors appear safe and hold promise for secondary prevention in myocardial infarction and ischaemic stroke, with ongoing phase III trials assessing their broader efficacy and safety. This Review discusses the rationale, pharmacology, evidence and future directions of factor XI inhibitors across various clinical settings. Inhibition of factor XI has emerged as a promising strategy to mitigate bleeding while potentially preserving antithrombotic efficacy. In this Review, the authors comprehensively discuss the rationale, pharmacology, evidence and future directions for factor XI inhibitors across various clinical settings.

BACKGROUND:The COMPLETE trial demonstrated a reduction in cardiovascular (CV) death or new myocardial infarction (MI) after complete, rather than culprit-only, revascularisation in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). However, it is unknown whether this benefit varies according to baseline left ventricular ejection fraction (LVEF). AIMS:We aimed to determine the effects of complete versus culprit-only revascularisation according to LVEF. METHODS:Baseline LVEF was available for 2,214 of 4,041 randomised patients. The effect of both strategies on the first co-primary outcome of CV death or new MI and the second co-primary outcome of CV death, new MI, or ischaemia-driven revascularisation (IDR) was determined within the prespecified LVEF ranges of <45% (N=660) and ≥45% (N=1,554). An analysis of clinical outcomes by LVEF according to thirds was also conducted. RESULTS:Patients with LVEF <45% experienced a significantly higher incidence of the first co-primary outcome compared with those with LVEF ≥45% (4.2%/year vs 2.8%/year; hazard ratio [HR] 1.51, 95% confidence interval [CI]: 1.15-1.98; p=0.003). Compared with a culprit-only strategy, complete revascularisation consistently reduced the first co-primary outcome in patients with LVEF <45% (3.0%/year vs 5.5%/year; HR 0.55, 95% CI: 0.36-0.86) and those with LVEF ≥45% (2.4%/year vs 3.2%/year; HR 0.74, 95% CI: 0.52-1.04; interaction p=0.31). Complete revascularisation also consistently reduced the second co-primary outcome in patients with LVEF <45% (3.5%/year vs 7.3%/year; HR 0.49, 95% CI: 0.33-0.74) and those with LVEF ≥45% (2.7%/year vs 6.3%/year; HR 0.44, 95% CI: 0.33-0.60; interaction p=0.67). Consistent results were observed for both co-primary outcomes when LVEF was further stratified into categories of LVEF ≤35%, 36-49% and ≥50%. CONCLUSIONS:Among patients presenting with STEMI and MVD, those with reduced LVEF are at higher risk of ischaemic events than patients with preserved LVEF. There is a consistent benefit of complete revascularisation regardless of baseline LVEF.

Importance Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y(12 )inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y(12) inhibitor. Objective To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

BackgroundTicagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis.ObjectivesThis study sought to determine the effect of ticagrelor on limb events.MethodsPatients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline.ResultsOf 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; Pinteraction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (Pinteraction = 0.40) or TIMI major bleeding (Pinteraction = 0.3239).ConclusionsPatients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795)

Background: Transcatheter edge to edge repair (TEER) is an established treatment for patients with symptomatic severe functional MR on optimal medical therapy or severe symptomatic primary MR and high surgical risk. Renal dysfunction is associated with adverse outcomes but the threshold at which risks rise are uncertain. Aim To determine the association of estimated glomerular filtration rate (eGFR) with adverse outcomes in patients undergoing TEER for severe symptomatic mitral regurgitation (MR) in Ontario, Canada. Methods: This was a population-based retrospective cohort study using linked administrative datasets of patients who underwent TEER in Ontario, Canada, between 2011 and 2023. The key exposure was eGFR, which was modeled using restricted cubic splines. Outcomes were 1-year mortality, cardiovascular mortality (CV) and heart failure hospitalization (HF). Cause-specific hazards regression was used to model the association between eGFR and outcomes, utilizing eGFR 30ml/min/1.73m2 as the reference value. Results: We studied 2076 patients, of whom 294 (14.2%) had eGFR <30ml/min/1.73m2 and 841 (40.5%) had eGFR 30-60ml/min/1.73m2. The incidence at one year was 16.8% for all-cause mortality, 11% for CV mortality and 14.2% for HF hospitalizations. The Figure illustrates that the predicted incidence of adverse outcomes increases with lower eGFR, with subtle differences in patterns of change in risk at lower eGFR levels such that all-cause mortality and CV mortality begin to rise rapidly at eGFR values ≤30ml/min/1.73m2, while HF hospitalization increases linearly at eGFR ≤50ml/min/1.73m2. Conclusions: There was a progressive increase in all-cause, CV mortality and HF hospitalization after TEER for patients with lower eGFR, particularly those with values <30 ml/min/1.73m2. This data can inform patient discussions and guide post-procedural follow-up.

Abstract Background In the Complete Revascularization with Multivessel PCI for Myocardial Infarction (COMPLETE) trial, patients with ST-segment-elevation myocardial infarction (MI) who underwent staged revascularization of non-culprit coronary stenoses experienced fewer major adverse cardiovascular events than those who underwent a culprit-only approach (1). Inclusion was, however, based on angiographic and not physiological criteria. Purpose To analyse, using computational modelling, the physiological significance of non-culprit lesions included in the COMPLETE trial, to compare these against angiographic measures of severity, and investigate interactions between physiology and the benefits of complete revascularization. Methods Angiograms with appropriate digital imaging and communications in medicine (DICOM) data from the COMPLETE trial (n=1327) underwent software-based 3-dimensional (3D) arterial reconstruction and analysis of 3D-quantitative coronary angiography (QCA) and virtual fractional flow reserve (vFFR) using computational fluid dynamics software. Physiological lesion significance was defined as vFFR ≤0.80 and was compared with operators’ visual angiographic analysis, core-laboratory 2D-QCA and 3D-QCA. Results vFFR was computed successfully in 635 patients (710 lesions). The median vFFR was 0.82 (interquartile range 0.73–0.91). 302 patients (48%) had at least one physiologically significant lesion and 333 (52%) had none. 321 (45%) lesions were physiologically significant and 389 (55%) were not. Physiologically significant lesions were angiographically more severe than non-significant lesions according to the operator’s visual angiographic assessment (mean stenosis 80% vs. 75%, P<0.0001), 2D-QCA (69% vs. 59%, p<0.0001), and 3D-QCA (56% vs. 43, P<0.0001). Percentage lesion stenosis was significantly different when measured visually, with 2D-QCA and with 3D-QCA (80% vs 62% vs 49%, P<0.0001). vFFR was weakly correlated with operators’ visual angiographic severity (Figure 1) and 2D-QCA, but more strongly with 3D-QCA (r=-0.21, -0.21, and -0.60, respectively; all p<0.0001). 3D-QCA predicted vFFR significance more accurately than visual and 2D-QCA (concordance 73% vs 49% vs 59%, respectively). There was no statistically significant interaction between physiological lesion significance and any of the trial coprimary or key secondary clinical outcomes, or on an exploratory outcome of ischaemia-driven revascularization without preceding MI (all interactions P>0.30) (Figure 2). Conclusions In this virtual physiological substudy of the COMPLETE trial, 52% of patients lacked any physiologically-significant lesions, 3D-QCA was a better predictor of physiological significance than either 2D-QCA or operator visual analysis, and the benefits of complete revascularization appeared to be independent of physiological lesion significance. Further research is warranted to compare angiography-guided and physiology-guided complete revascularization strategies.Figure 1.Figure 2.