Abstract Background Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) carries increased risk for worse outcome. There is limited data on whether race and/or ethnicity affect outcomes. Materials and methods We included patients who underwent CTO intervention from 2012 to 2017 at The Mount Sinai Hospital (New York). Data were collected prospectively but examined retrospectively. The patients were stratified by race/ethnicity in Caucasians, African Americans, Asians and Hispanics. The primary end point was major adverse cardiac events (MACE) defined as the composite of death, myocardial infarction (MI), and target vessel revascularization (TVR) at 1 year follow-up. Secondary outcomes included individual components of the MACE (death, MI or TVR), and bleeding. Results A total 1,684 patients were included of which (49.8%) were Caucasians, 168 (10%) were African Americans, 396 (23.5%) were Asians and 281 (16.7%) were Hispanics. African Americans had the highest proportion of female patients (39%) and more often had a history of smoking (26.2%) and insulin-dependent diabetes mellitus (46.6%) compared to the other groups. They had the highest prevalence of in-stent restenosis as the target lesion (Table 1). Caucasians were older (65.9±11.1 years) with more calcified lesions and longest lesion length compared to the other groups. Asians had highest prevalence of multi-vessel coronary disease. Caucasians and Asians had higher Syntax score and more stents implanted. Procedural success was similar between the groups (Table 1). Adjusted analyses did not show any differences in clinical outcomes between groups (Table 2). Conclusion In spite of many differences between racial/ethnical groups in baseline and procedural characteristics, procedural success of CTO intervention and 1-year MACE rates were similar between groups.Procedural characteristicsAdjusted 1-year outcomes

Abstract Background Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) and low grade vascular inflammation, commonly quantified using high-sensitivity C-reactive protein (hsCRP), have been demonstrated to be causal in the development of atherosclerotic disease. Whilst recent large-scale trials have investigated the relative impact of LDL-c and inflammation on cardiovascular outcomes, there is a scarcity of data in real-world patients undergoing percutaneous coronary intervention (PCI). Purpose To investigate the relative drivers of residual risk in patients with established statin treatment undergoing PCI in a contemporary large-scale cohort. Methods From January 2012 to February 2020 patients undergoing PCI at a tertiary center were included for current analysis. Patients were categorized into 4 subgroups according to different combinations of LDL-c and hsCRP concentrations at baseline: no residual cholesterol or inflammatory risk (LDL-c <70 mg/dL + hsCRP <2 mg/L), residual cholesterol risk (LDL-c ≥70 mg/dL + hsCRP <2 mg/L), residual inflammatory risk (LDL-c <70 mg/dL + hsCRP ≥2 mg/L), and combined residual cholesterol and inflammatory risk (LDL-c ≥70 mg/dL + hsCRP ≥2 mg/L). Individuals who presented with acute myocardial infarction, neoplastic disease and hsCRP concentrations >10 mg/l were excluded. The outcome of interest was major adverse cardiac events (MACE - composite of all-cause mortality, myocardial infarction, or stroke). A univariable cox regression model was calculated. Results Overall, 10,845 patients were included. In total, 3,210 patients displayed neither cholesterol nor inflammatory risk and 3,059 individuals had elevated cholesterol risk only. In 1,839 patients an inflammatory risk was noted, whilst 2,737 patients presented with combined cholesterol and inflammatory risk. Kaplan-Meier curves for 1-year follow-up are displayed in Figure 1. Patients with residual inflammatory risk had the highest event rate of the composite endpoint (5.2%), followed by patients with combined residual risk (3.5%), individuals with residual cholesterol risk (2.3%) and persons with neither cholesterol nor inflammatory risk (2.4%; p<0.0001 for log rank test across all groups). An association with MACE was solely documented for patients with residual inflammatory risk (HR: 2.09, 95% CI: 1.52 - 2.88; p<.001), and also borderline significant for combined cholesterol and inflammatory risk (HR: 1.41, 95% CI: 1.03 - 1.95; p=0.034), whilst this was not the case for patients with elevated cholesterol risk only (see Figure 2). Conclusion In a contemporary real-world cohort of statin treated patients undergoing PCI, inflammation irrespective of LDL-c concentrations was the driver for adverse cardiovascular outcomes. This data might be helpful to further define target populations for both intensified lipid-lowering as well as anti-inflammatory treatment approaches.

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR < 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Abstract Background Systemic inflammation enhances atherosclerosis progression and is a well-established determinant of cardiovascular risk. High-sensitivity C-reactive protein (hsCRP), the most widely available biomarker of inflammation, has indeed been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). However, some heterogeneity exists in the threshold to define high hsCRP associated with increased cardiovascular risk, with the 2 and 3 mg/L cut-offs being used more commonly. Purpose We aimed to evaluate the clinical impact of systemic inflammation in patients undergoing PCI across the spectrum of baseline hsCRP values. Methods We retrospectively evaluated consecutive patients undergoing PCI with drug-eluting stent implantation from 2012 to 2022 at Mount Sinai Hospital (NY, USA). We excluded patients presenting with acute myocardial infarction or active cancer and those for whom baseline hsCRP was not available or was above 10 mg/L. Patients were stratified into three groups according to baseline hsCRP levels: <2.0, 2.0 to 3.0, and >3.0 mg/L. We estimated the risk of 12-month adverse events using the lowest hsCRP group (<2.0 mg/L) as reference. The primary endpoint was MACCE, defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACCE individual components, target vessel revascularization (TVR), stent thrombosis and bleeding. Results A total of 10,811 patients were included in the analysis. Of these, 6,210 (57.4%) had hsCRP <2.0 mg/L, 1,624 (15.0%) between 2 and 3 mg/L and 2,977 (27.6%) >3.0 mg/L. Incidence of anemia, diabetes mellitus, peripheral and cerebrovascular artery disease, atrial fibrillation and chronic kidney disease increased stepwise across hsCRP groups. Moreover, patients with higher hsCRP tended to present more frequently with unstable angina and higher baseline LDL cholesterol levels. As regards procedural variables, coronary artery disease severity and PCI complexity did not differ significantly across groups. When compared with patients with hsCRP < 2, hsCRP > 3 mg/L was associated with a greater adjusted risk of MACCE (4.9% vs 2.4%; HR 1.75 % CI 1.35 - 2.28), all-cause death (2.5% vs 0.9%, HR 2.34, 95%CI 1.57-3.47) and MI (2.5% vs 1.3%; HR 1.58 95%CI 1.11-2.26) (Figure 1). Risks of stroke, TVR, stent thrombosis and bleeding did not significantly differ across hsCRP groups (Table 1) Conclusions In patients undergoing PCI, elevated hsCRP values exceeding 3 mg/L exhibit a more robust association with the risk of MACCE and all-cause mortality, as compared with both hsCRP < 2.0 and between 2.0 and 3.0 mg/L. In this context, the use of hsCRP might improve the stratification of patients associated with higher inflammatory burden.

With an emphasis on shared decision-making in revascularisation guidelines, patients with multivessel coronary artery disease (CAD) may prefer PCI over CABG, despite Heart Team recommendations. We compared the risk of adverse events in patients with multivessel disease who undergo PCI according to patient preference or Heart team recommendations. Consecutive stable ischaemic heart disease patients undergoing catheterisation with a SYNTAX score >22 or 3-vessel CAD, and who underwent PCI following Heart Team assessment from 2013–2020 were included. Patients were divided into: a) PCI eligible by appropriate-use criteria (AUC-PCI); b) CABG-eligible but refused CABG (CABG-refusal); and c) CABG-ineligible. Primary endpoint was the composite of death, myocardial infarction or stroke at one-year. The study included 3,687 patients (AUC-PCI n=1,718 [46.6%], CABG-refusal n=1,595 [43.3%], CABG-ineligible n=374 [10.1%]). Crude rates of the primary outcome are shown in Figure 1. After multivariate risk adjustment, the risk of the primary composite outcome was significantly higher in the CABG-refusal (HR 1.67, 95%CI 1.08–3. 56, p=0.02) and CABG-ineligible patients (HR 3.26 [95%CI 1.28–3.65], p=0.004; reference group: AUC-PCI). Consistent effect sizes were seen in subgroup analyses including left main, diabetes and high SYNTAX score (>33) cohorts. In multivessel CAD patients undergoing PCI, cardiovascular event rates were significantly higher in patients that refused or were ineligible for CABG. Our findings provide real-world data to inform shared decision-making discussions in these patients.

Background Adjunctive techniques to modify calcium such as rotational atherectomy (RA) induce coronary artery trauma that may result in higher post-procedural troponin and creatinine kinase-MB (CK-MB) release. The clinical significance of these cardiac enzyme releases remains unclear. As such, we sought to examine the association of elevated cardiac enzymes with major adverse cardiac events (MACE). Methods Consecutive patients undergoing PCI with RA for chronic coronary syndromes and unstable angina between 2012 and 2019 were included. Our practice is to routinely measure pre and post-PCI troponin & CK-MB. Patients with a positive pre-PCI CK-MB or troponin were excluded. Elevated post-PCI enzymes were categorised as multiples of the enzyme normal upper reference limit (URL); Troponin: 1x-5x, 5x-35, 35x-70x, >70x, and CK-MB: 1x-3x URL, 3x-5x URL, 5x-10x URL, >10x URL. MACE was defined as all-cause mortality or MI at 1-year follow-up. Results A total of 2,697 patients (mean age 70.0 ±10.4 years, 27% female, 48% diabetic, mean SYNTAX score 19.3±11.5) met the inclusion criteria. The majority of patients presented with stable angina (57.2%), 73.9% of cases had multivessel disease, and 29.0% of cases involved a bifurcation. Troponin and CK-MB levels in excess of the URL were detected in 22.2% and 18.2% of cases, respectively. Overall 6.8% (n=184), 1.8% (n=49) and 1.2% (n=33) of patients met the 4th Universal definition of myocardial infarction (UDMI), SCAI and ARC-2 definitions of periprocedural myocardial infarction, respectively. Across troponin and CK-MB categories, there was a significant association with MACE at 1-year. An association emerged with CK-MB and troponin levels >5x the URL for each enzyme. A peak troponin of 35x-70x the URL was independently associated with an increased risk MACE at 1-year follow up (adjusted hazard ratio [AHR] of 3.68, 95%CI [1.14–11.9], p=0.03), figure 1A. No category of CK-MB release post-PCI was independently associated with MACE at 1-year follow-up, figure 1B. Conclusion Post-procedural cardiac enzyme elevation occurred in 1 in 5 patients undergoing RA. Higher levels of post-PCI troponin and CK-MB were associated with an increased risk of MACE. Increased vigilance during follow-up may be justified for this subset of patients undergoing PCI.

Abstract Background Periprocedural myocardial injury and spontaneous myocardial infarction (MI) are potential complications in patients with coronary artery disease. The prognostic impact of periprocedural myocardial injury as compared to that of spontaneous MI has not been fully assessed. Aim To assess the impact on mortality of periprocedural myocardial injury and spontaneous MI according to thresholds of troponin increase proposed in expert consensus documents. Methods Among patients undergoing PCI at a large volume center, we included those presenting with: 1) chronic coronary syndrome (CCS) with normal (≤1x upper reference level [URL]) cardiac troponin I (cTnI) at baseline and after PCI (no myocardial events); 2) CCS with normal baseline cTnI and increased (>1 URL) cTnI in the 48 hours after PCI (periprocedural myocardial injury), and 3) type I MI (spontaneous MI). Patients with missing cTnI values, patients with CCS and increased baseline cTnI (>1 URL) and patients with unstable angina were excluded. Patients with periprocedural myocardial injury and spontaneous MI were stratified in 4 groups according to the cTnI peak value: 1-5, 5-35, 35-70, >70 times (x) above the URL. The risk of all-cause death at 1-year after PCI was assessed across the cTnI strata using the group with no myocardial events as reference. The conventional cTnI was measured with the Architect methodology (Abbott, Chicago, Illinois) and the URL was 0.4 ng/mL. Results Among patients undergoing PCI between 2012 and 2019, 7602 had no myocardial events, 913 had periprocedural myocardial injury and 2192 presented with spontaneous MI. CTnI peak was 1-5x, 5-35x, 35-70x, >70x above URL in 53%, 41%, 4%, 2% of patients with periprocedural myocardial injury, respectively, and in 24%, 38%, 11%, 26% of patients with spontaneous MI, respectively (Figure 1). Rate of all-cause death was 1.4% in patients with no myocardial events. The risk of all-cause death at 1-year was increased after periprocedural myocardial injury with a peak cTnI of 35-70x URL and tended to be higher with a peak cTnI >70x URL (Figure 2). Among patients with spontaneous MI, the risk of all-cause death was significantly higher in all cTnI strata (Figure 2). Adjusted results and p-value for comparisons between periprocedural myocardial injury and spontaneous MI will be presented at ESC 2023. Conclusions All-cause death at 1-year was not increased after periprocedural myocardial injury with a peak cTnI ≤35x URL. Periprocedural myocardial injury with cTnI peak >35x URL and spontaneous MI with any cTnI elevation were associated with a similar crude risk of all-cause death.Figure 2

Abstract Background/Introduction In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban (EDX) was noninferior to vitamin K antagonists (VKAs) for preventing most adverse clinical events but was associated with increased major bleeding (MB). Presence of EDX dose reduction criteria applied in the trial (DRC; body weight ≤60 kg, CrCL 15–50 mL/min, concomitant use of selected P-glycoprotein-inhibitors) indicates a more vulnerable patient phenotype. Purpose Compare clinical outcomes after TAVI for AF patients with and without DRC stratified by anticoagulation strategy and age. Methods ENVISAGE-TAVI AF (NCT02943785) was a multicentre, open-label, randomised, controlled trial comparing EDX vs VKA in patients with AF as the indication for oral anticoagulation (OAC) after successful TAVI. In this analysis, outcomes—which included net adverse clinical events (NACE; composite all-cause death, myocardial infarction, ischaemic stroke, systemic thromboembolic event, valve thrombosis, or MB), intracranial haemorrhage, ischaemic stroke, all-cause death, cardiovascular (CV) death, non-CV death, MB bleeding, fatal MB bleeding, and major gastrointestinal bleeding (MGIB) —were compared in patients with vs without DRC, further stratified by OAC use, and age (< or ≥80 years [y]). Results Patients meeting DRC (n=637) were older, more often female, and had lower baseline CrCL than those without (n=740). In addition, these patients had significantly higher rates of NACE (P=0.0375) and all-cause death (P=0.0136). There were no differences in MB or MGIB rates between patients with vs without DRC. EDX resulted in more MB (hazard ratio [95% CI], 1.6 [1.1–2.5] and MGIB (2.6 [1.2–5.8]) than VKA only in patients without DRC. In patients aged <80 y meeting DRC, rates of all-cause death (P=0.0366) and CV death (P=0.0042) were significantly higher than those without DRC. Among patients aged <80 y, there were no differences in rates of clinical outcomes between EDX and VKA regardless of the presence or absence of DRC; Figure 1). In patients aged ≥80 y, there were no differences in rates of all-cause death, MB, or MGIB in those with or without DRC; Figure 2). Additionally in this age group, there was no difference in MB between patients on EDX and VKA both with and without DRC. However, there was more MGIB with EDX when there were no DRC. In patients aged ≥80 y with DRC, all-cause death was lower with EDX. Conclusions In this subanalysis of ENVISAGE-TAVI AF, the presence of DRC indicates a more vulnerable patient phenotype at higher risk for all-cause death after TAVI and in whom a lower EDX dose may have substantial benefits in terms of outcomes, including bleeding events, particularly in patients ≥80 y.Figure 1Figure 2

Repeat coronary revascularization is a common adverse event after successful percutaneous cor-onary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomiza-tion. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clini-cally relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confi-dence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high -risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).(c) 2023 Elsevier Inc. All rights reserved.

Abstract Background Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain at increased risk of recurrent ischemic events. An abbreviated dual antiplatelet therapy (DAPT) duration as short as 1 month has been suggested for those at high bleeding risk (HBR). Whether the benefits of 1-month DAPT are preserved in HBR patients presenting with non-ST-elevation ACS (NSTE-ACS) is subject of debate. Purpose To assess the impact of NSTE-ACS presentation on the ischemic and bleeding outcomes of HBR patients undergoing PCI with a cobalt-chromium everolimus-eluting stent followed by a 1-month versus 3-month DAPT. Methods The XIENCE Short DAPT Program encompasses three prospective, international, single-arm studies evaluating the safety and efficacy of a 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT duration. The program enrolled HBR patients who had undergone successful XIENCE stent implantation for acute or chronic coronary syndrome (excluding ST-elevation ACS). Event-free subjects discontinued DAPT at 1 or 3 months post-PCI. The primary endpoint was the composite of all-cause death or myocardial infarction (MI), while the key secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding between 1 and 12 months post-PCI. Ischemic and bleeding events associated with 1-month versus 3-month DAPT were assessed according to clinical presentation using propensity-score (PS) adjustment. Results Out of 3,364 HBR patients (n=1,392 on 1-month DAPT and n=1,972 on 3-month DAPT), 1164 (34.6%) underwent PCI for NSTE-ACS. At 12 months, the risk of death or MI was similar between 1- and 3-month DAPT in patients with (adjHR 1.12, 95% CI 0.73–1.70) and without NSTE-ACS (adjHR 0.92, 95% CI 0.65–1.29; p-interaction = 0.33). Landmark analysis between 1 and 3 months post-PCI showed significant treatment effect modification according to clinical presentation (p-interaction = 0.03) with greater benefit of 1-month DAPT in stable patients. BARC 2–5 bleeding was consistently reduced in both NSTE-ACS (adjHR 0.58, 95% CI 0.38–0.90) and stable patients (adjHR 0.86, 95% CI 0.63–1.18; p-interaction = 0.15). Conclusions Among HBR patients undergoing PCI with an everolimus-eluting stent, 1-month compared with 3-month DAPT was associated with similar 1-year risk of ischemic events and reduced bleeding, irrespective of clinical presentation. Between 1 and 3 months post-PCI, however, stable patients seemed to derive greater net benefit from 1-month DAPT compared to those with NSTE-ACS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Abstract Background The Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) randomized clinical trial demonstrated that in selected high risk patients who took ticagrelor and aspirin for 3 months after percutaneous coronary intervention (PCI), continuing ticagrelor alone was associated with significantly less bleeding events than ticagrelor plus aspirin and did not lead to ischemic harm over a period of 1 year (1). The prevalence and risk of adverse events of patients fulfilling the TWILIGHT inclusion criteria in real-world setting is unclear. Purpose To elucidate the prevalence and prognosis of patients fulfilling the TWILIGHT inclusion criteria. Methods Patients that received at least one drug eluting stent in a coronary artery at a large tertiary center (Mount Sinai Hospital, New York) were considered for inclusion. As in the TWILIGHT trial, individuals on chronic oral anticoagulation treatment, with STEMI, cardiogenic shock, on dialysis, with prior stroke, or platelet count <100,000 were excluded. Patients were stratified in two groups: 1) TWILIGHT-like patients, who met at least one clinical (age ≥65 years, female sex, established vascular disease, diabetes mellitus, estimated glomerular fraction rate <60mL/min, acute coronary syndrome with troponin increase) and one angiographic (multivessel coronary artery disease [CAD], stent length >30mm, thrombotic target lesion, bifurcation requiring 2 stents, left main or proximal left anterior descending artery lesion, atherectomy device use, SYNTAX score ≥23) TWILIGHT inclusion criterion; 2) Non-TWILIGHT-like patients, who did not fulfil at least one clinical and one angiographic TWILIGHT inclusion criterion. The primary outcome was a composite of death, myocardial infarction (MI), stroke. Secondary outcomes included bleeding, components of the primary outcome, target vessel and target lesion revascularization, stent thrombosis. All events were assessed at 1 year after PCI. Results Out of 30,470 patients undergoing PCI between 2012 and 2019, 13,236 were included in the current analysis. TWILIGHT criteria were met in 11,018 (83%) patients. Established vascular disease and multivessel CAD were the most frequently fulfilled criteria. At 1 year, TWILIGHT-like patients were at higher risk for the primary outcome (3.2% vs 1.1%, HR 2.85, 95% CI 1.83–4.44), severe bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32–2.62), all-cause death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70–7.77), myocardial infarction (1.8% vs 0.6%, HR 2.81 95% CI 1.56–5.04), TVR (7.8% vs 4.1%, HR 1.94, 95% CI 1.53–2.47), TLR (5.1% vs 1.7%, HR 2.98 95% CI 2.07–4.29). Stent thrombosis and stroke rate were generally low and did not differ between patients meeting or not the TWILIGHT inclusion criteria. Conclusion Among all-comer patients undergoing PCI, the fulfillment of the TWILIGHT inclusion criteria is frequent and is associated with a higher risk of death, ischemic and bleeding complications Funding Acknowledgement Type of funding sources: None.

Abstract Background Patients with atrial fibrillation (AF) and concomitant coronary artery disease are at increased risk for poor outcomes. Less is known about specific causes of death in this population. Methods We describe specific causes of death among patients with AF and acute coronary syndrome and/or percutaneous coronary intervention included in the AUGUSTUS trial and followed for 6 months. An independent clinical events committee, blinded to treatment assignment, adjudicated cause of death according to pre-defined criteria. The association between baseline factors and all-cause death was evaluated using Cox proportional hazards modeling. Results A total of 151 deaths occurred in 4614 patients and were adjudicated as follows: 111 (73.5%) deaths due to cardiovascular (CV) causes and 40 (26.5%) due to non-CV causes. The most common cause of CV death was sudden death (n=39 [35.1%]), followed by myocardial infarction (n=29 [26.1%]) and heart failure (n=24 [21.6%]). The most common causes of non-CV death were infection (n=11 [27.5%]), bleeding (n=8 [20.0%]), and malignancy (n=5 [12.5%]). Increasing age, African American race, history of heart failure, treatment with diuretics, and lower body weight were associated with an increased risk of all-cause death (Table). Conclusions Among patients with AF and coronary artery disease, cardiovascular causes were responsible for the majority of deaths within 6 months. Our findings provide relevant information to inform the design of future studies in this population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AUGUTUS was funded by Bristol Myers Squibb and Pfizer.

Abstract Background The TWILIGHT trial demonstrated a reduction in BARC 2, 3 or 5 (BARC-235) bleeding without an increase in ischemic events at 1-year in high-risk PCI patients randomized to placebo or aspirin (ASA) on a background of ticagrelor 3-months after PCI. However, the effect of ASA discontinuation according to baseline risk of bleeding and ischemic events remain unclear. Purpose To a) develop separate models to predict the risk of bleeding and ischemic events, and b) to assess treatment effect of ASA discontinuation across the risk strata. Methods Using the TWILIGHT patient database (N=7,119), two multivariable models, one for BARC-235 bleeding and one for CV death, nonfatal MI or nonfatal ischemic stroke (ischemic endpoint) were developed, and their predictive capacity was assessed. The effect of randomized treatment on bleeding and ischemic events across different patient risk-group categories as determined by the risk scores was investigated. Results At 1-year, 350 (5.4%) patients experienced a BARC-235 bleeding event and 258 (3.6%) experienced an ischemic event. Independent predictors of BARC-235 included haemoglobin levels at index PCI, proton-pump inhibitor non-use at discharge, age, liver disease and active smoking (c-statistic 0.64). Independent predictors of the ischemic outcome included a positive troponin ACS, prior CABG, diabetes, age, peripheral artery disease, prior PCI, a history of congestive heart failure, active smoking, the level of index PCI complexity, and prior MI (c-statistic 0.71). The risk of a BARC-235 almost doubled between patients in lower versus higher bleeding risk categories (4.3% versus 7.9%) and ischemic risk more than tripled between patients in lower versus higher ischemic risk categories (2.0% versus 7.0%) (see Figure 1). There was no evidence of a differential treatment effect for dual antiplatelet therapy versus ticagrelor monotherapy across the different risk categories of bleeding (interaction P=0.54) and ischemic risk (interaction P=0.95) (Table 1). Conclusion Individual patient bleeding and ischemic risks after PCI can both be readily characterised with good discrimination. The effect of ASA discontinuation in preventing bleeding in ticagrelor-treated patients was consistent regardless of baseline bleeding risk. There was no evidence for increased ischemic events with ASA discontinuation according to baseline ischemic risk. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AstraZenecaIcahn School of Medicine at Mount Sinai

Abstract Background Recent advances in drug eluting stents (DES) design have significantly decreased the rates of in-stent restenosis (ISR). Nonetheless, ISR remains a major problem, affecting 5–10% of patients undergoing percutaneous coronary intervention (PCI). Furthermore, PCI for ISR is often a poor prognostic factor for outcomes after the procedure. Historically, obese patients tended to have better outcomes when undergoing PCI, however it is unclear if this trend continues for the same population undergoing PCI for ISR. Purpose Investigate the outcomes of patients undergoing PCI for ISR in the overweight and normal weight population. Methods All patients undergoing PCI with DES implantation at a tertiary care center from January 2012 to December 2019 were included. Normal weight was defined as a body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than 25 kg/m2, while overweight was defined as a BMI greater than or equal to 25 kg/m2. Patients with BMI <18.5 kg/m2, underwent PCI for acute myocardial infarction (MI), or received a bare metal stent (BMS) were excluded. The primary outcome was major events (MACE), a composite of all-cause mortality, myocardial infarction (MI), and target vessel revascularization (TVR) up to one year after PCI. Secondary outcomes included individual components of the primary endpoint. Results Out of 16,234 patients with available data on BMI, 12,444 (76.7%) were overweight and 3,790 (23.3%) were normal weight. Among overweight patients, 2,879 (23.1%) underwent PCI for ISR versus 815 (21.5%) of normal weight patients. Regardless of BMI status, patients undergoing PCI for ISR had higher rates of co-morbidities such as hypertension, hyperlipidemia, and diabetes mellitus than non-ISR counterparts. At one year post PCI, both overweight and normal weight patients undergoing PCI for ISR had increased risk of MACE (overweight: 18.4% vs. 6.7%; HR 2.83; 95% CI 2.50–3.20; normal weight: 18.8% vs. 7.8%, HR 2.43, 95% CI 1.95–3.04) when compared to non-ISR counterparts, mostly driven by TVR (overweight: 16% vs. 4.6%; HR 3.58; 95% CI 3.11–4.13; normal weight: 15.2% vs. 4.1%; HR 3.69; 95% CI 2.80–4.86). However, only overweight patients undergoing PCI for ISR had higher risk of all cause mortality (2.2% vs. 1.5%; HR 1.42; 95% CI 1.03–1.95) and MI (3.0% vs. 1.3%, HR 2.22; 95% CI 1.64–2.99) when compared to non-ISR counterparts (Figure 1). Conclusions PCI for ISR was associated with increased risk of MACE, irrespective of body weight. The risks of all-cause mortality and MI in ISR vs non-ISR patients only reached statistical significance in overweight patients. Funding Acknowledgement Type of funding sources: None.