Risk Of Bleeding Research Articles

Peripheral artery disease, antithrombotic treatment and outcomes in European and Asian patients with atrial aibrillation: a report from 2 prospective observational registries

Abstract Background In patients with atrial fibrillation (AF), the impact of peripheral artery disease (PAD) on oral anticoagulant (OAC) therapy use and the risk of outcomes remains unclear. Objective To analyse the epidemiology of PAD in a large cohort of European and Asian AF patients, and the impact on treatment patterns and risks of adverse outcomes. Methods We analysed AF patients from two large prospective observational registries. We identified patients with PAD as reported by the investigators. Logistic regression analysis was used to assess factor associated with the presence of PAD at baseline. OAC prescription and risk of outcomes were analyzed according to the presence of PAD, using adjusted Logistic and Cox regression analyses. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Interaction analyses were also performed according to different subgroups. Results 15,497 patients with AF (mean age 68.9, SD 11.6 years; 38.6% female, 30% from Asia) were included in the analysis. PAD was found in 941 patients (6.1%), with higher prevalence among European individuals compared to Asian (8.1% vs 1.2%, p<0.001). Patients with PAD were older, more likely with permanent AF, more symptomatic and with higher thromboembolic and bleeding risk. On logistic regression analysis, European patients had 6-fold higher odds of presenting with PAD compared with Asians (Figure 1, Panel A). Other comorbidities and increasing age were associated with higher odds of prevalent PAD (Figure 1 Panel A). Conversely, female sex was associated with lower odds of having PAD at baseline. With age modelled as a continuous variable, and odds of PAD at baseline, there was a non-linear relationship, with the odds of PAD increasing almost linearly until 70 years, plateauing afterwards (Figure 1 Panel B). After adjustments, PAD was associated with lower use of OAC (OR 0.69, 95% CI 0.57-0.85). On Cox regression analysis, PAD was associated with a higher risk of the primary composite outcome (HR 1.28, 95%CI: 1.08-1.52) and all-cause death (HR 1.40, 95%CI: 1.16-1.69). A significant interaction was observed between PAD and age, with greater risks of PAD found in younger patients (<65 years) for the primary outcome (pint=0.014, Figure 2, panel A). Consistent results were observed when we analysed the interaction between PAD and age, modelled as a restricted cubic spline, where the risk of the primary outcome followed a J-curve across age, while patients without PAD showed an approximately linear relationship (pint<0.001, Figure 2, Panel B). Conclusions In patients with AF, PAD is associated with lower use of OAC and higher risk of adverse outcomes, with a greater risk seen in younger patients.Figure 1Figure 2

Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis

Abstract Introduction and purpose transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding. Methods a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed. Results 184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale. Conclusions bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.

Preclinical characterisation and first-in-human results on the tolerability and pharmacodynamic effect of REGN9933, a monoclonal antibody targeting the factor XI/activated factor XI apple 2 domain

Abstract Background/Introduction Standard-of-care anticoagulants are associated with increased bleeding risk. Genetic/pharmacological data suggest coagulation factor XI (FXI) inhibition can prevent thrombosis with minimal increased bleeding risk. We present preclinical and first-in-human (FIH) data on REGN9933, a FXI-binding monoclonal Ab. Purpose To characterise REGN9933 epitope binding sites, affinities for FXI and activated FXI (FXIa), and effect on high molecular weight kininogen (HMWK)’s interaction with FXI. Also, to assess safety, tolerability and pharmacodynamics in healthy human participants (pts). Methods Epitope binding sites mapped with cryogenic electron microscopy, binding affinities determined with plasmon resonance techniques, effect on thrombin generation assessed with a thrombin generation assay, and impact on HMWK:FXI interaction analysed using ELISAs. In the FIH, Ph 1, randomised, double-blind, single-centre study, pts received a single dose of REGN9933 intravenously (IV; 3–300 mg) or subcutaneously (SC; 100 mg & 300 mg), or placebo (PBO). Primary endpoint: incidence and severity of treatment-emergent AEs (TEAEs). Other endpoints: effect of REGN9933 on activated partial thromboplastin time (aPTT) and prothrombin time (PT) to assess intrinsic and extrinsic pathway-triggered coagulation, respectively; and FXI activity. Results REGN9933 was found to bind the FXI apple 2 domain, with subnanomolar binding affinities for FXI and FXIa at 37°C, resulting in reduced thrombin generation from the intrinsic (not extrinsic) pathway. REGN9933 competed with HMWK for FXI binding in a dose-related manner. In the Ph 1 study, 56 pts received REGN9933 (IV, n=30; SC, n=12) or PBO (n=14); 42.9% and 21.4% had ≥1 TEAE, respectively (most common with REGN9933: headache, 12%; oropharyngeal pain, 5%). No serious/severe TEAEs, or TEAEs of special interest (inc. moderate/severe bleeding) reported. Laboratory tests revealed no clinically meaningful differences in the number/type of treatment-emergent potentially clinically significant values with REGN9933 vs PBO. REGN9933 resulted in dose-dependent prolongation of aPTT; aPTT mean fold change from baseline was highest with IV 300 mg after 8 hrs (2.7) and remained >2 for 36 days (Fig 1). There was no detectable effect on PT or clinically meaningful effect on bleeding time. REGN9933 supressed FXI activity in a dose-dependent manner, with suppression to approx. the lower limit of assay quantification (5%) with IV ≥30 mg (Fig 2). Conclusion(s) REGN9933 binds the FXI apple 2 domain and inhibits HMWK:FXI interaction, preventing intrinsic pathway-triggered FXI activation. FIH data showed dose-dependent inhibition of the intrinsic coagulation pathway by REGN9933, without affecting the extrinsic or common pathways. Pharmacodynamic and safety findings support continued development of REGN9933 as an anticoagulant that may carry less bleeding risk than currently approved agents.

Cluster-specific risk factors for suboptimal thromboprophylaxis in contemporary European cohort of patients with atrial fibrillation: the EHRA-PATHS Project

Abstract Background Oral anticoagulation (OAC) is essential to optimal thromboprophylaxis in patients with atrial fibrillation (AF). Owing to bleeding risk concerns, OAC use may be challenging in clinically complex high-risk AF patients. Comorbidities might lead to suboptimal OAC use. We assessed cluster-specific risk factors for non-prescribing OAC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was constructed using data from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific risk factors for non-prescribing OAC were identified using univariate and multivariate logistic regression analyses. Results Of 18.799 patients, 2086 (11.1%) were not prescribed with OAC. Among the three clusters (see Table), OAC non-prescribing was significantly more prevalent in Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) or Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), both P<0.001, with no significant difference between Clusters 2 and 3 (P=0.161). Cluster-specific multivariable risk factors for non-prescribing OAC are shown in Table. In all three clusters AF clinical type was significantly associated with OAC non-use. In Cluster 1, OAC non-use was less likely in the presence of CHA2DS2-VASc stroke risk factors, while bleeding risk factors were predominant multivariable predictors of OAC non-use among elderly (Clusters 2 and 3). Conclusion Our findings in a large contemporary European cohort suggest that different considerations prevail in treatment decision on OAC use in AF patients in clinical practice, depending on patient’s age and AF clinical type, as well as the presence and type of underlying comorbidities. Our findings could help in formulating targeted interventions to optimize stroke prevention in different subgroups of AF patients.

Risk score guided dual antiplatelet therapy duration in patients with acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background The use of risk scores to guide the duration of dual antiplatelet therapy(DAPT) in patients with acute coronary syndrome(ACS) is recommended in current guidelines, however clinical data on the impact of its prospective use is lacking. Purpose To compare risk-score guided DAPT duration to standard of care in ACS patients. Methods Since 2015, patients with ACS are enrolled in the prospective FORCE-ACS registry. In 2018, we implemented a risk score-guided approach for DAPT duration. In this analysis, we compared patients in which DAPT duration was guided by bleeding and ischemic risk assessment using PRECISE-DAPT-scores and DAPT-scores to a standard treatment group in a 1:4 ratio. In risk score-guided patients, high bleeding risk patients(HBR) were advised short DAPT(≤6 months); patients without HBR or high ischemic risk(HIR) were advised 12 months DAPT; and patients without HBR but with HIR were advised prolonged DAPT(≥30 months). In the standard treatment group DAPT duration was left at the discretion of the treating physician. Exclusion criteria included no DAPT or oral anticoagulation at discharge or implanted bio-vascular stents. Primary outcome was a composite of all-cause mortality, myocardial infarction(MI), stent thrombosis(ST), stroke and Bleeding Academic Research Consortium(BARC) 3 or 5 bleeding; a secondary composite ischemic outcome consisted of cardiovascular mortality, MI, ST and ischemic stroke. Kaplan-Meier plots with log-rank testing and Cox proportional hazard regression after adjustment of potential confounders were performed for the primary outcome. Sensitivity analyses were performed for patients included after implementation of the risk score-guided approach and for censoring events within the first six months. Results Between 2015 and 2020 8,009 patients were enrolled in the FORCE-ACS registry, of which 5,518 patients were included for analysis. The risk-score guided group(n=1,200) more often presented with ST-elevation MI, percutaneous coronary intervention or optimal medical therapy, while standard treatment patients(n=4,318) were older, more often had prior MI, prior revascularization, received coronary artery bypass grafting or conservative management. In the risk-score guided group, 15.7% had HBR, 46.4% were without HBR or HIR, and 37.9% showed HIR without HBR. The primary outcome was 6.3%(n=75) in risk score-guided patients versus 14.8%(n=637) in the standard treatment group (adjusted hazard ratio(HR) 0.47 [95%CI 0.36–0.61], p<0.001). These results remained consistent after sensitivity analyses (fig 1B). Both the composite ischemic outcome(HR 0.54 [95%CI 0.41–0.72] p<0.001) and BARC 3 or 5 bleeding (HR 0.23 [95%CI 0.08-0.63], p=0.004) were significantly lower in risk score-guided patients compared to the standard treatment group. Conclusion In this prospective analysis, risk-score guided DAPT duration showed a significant reduction of both ischemic and bleeding events compared to standard treatment.

One-year clinical outcome of aspirin-free prasugrel monotherapy following stent implantation in patients with chronic coronary syndrome: insight from ASET-JAPAN study

Abstract Background Single antiplatelet therapy with a potent P2Y12 inhibitor without aspirin after coronary stent implantation may provide an adequate balance between ischemic and bleeding risks in selected patients. The 3-month follow-up of the Acetyl-Salicylic Elimination Trial (ASET)-Japan pilot study demonstrated the feasibility and safety of Prasugrel monotherapy without aspirin after successful percutaneous coronary intervention (PCI) in selected patients with chronic coronary syndrome (CCS). Purpose The current study aimed to evaluate the 1-year clinical outcome in the ASET-Japan. Methods The ASET-Japan pilot study was designed to demonstrate the feasibility and safety of the approved dose of prasugrel monotherapy in Japan without aspirin after optimal PCI with a platinum-chromium everolimus-eluting stent in CCS population. After successful procedure, all patients were treated with a locally approved maintenance dose of 3.75 mg/day of Prasugrel monotherapy up to 3-month. After 3-month, the choice of antiplatelet therapy was left to the discretion of the investigators. Patients were followed up to 1 year. The target lesion-related endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction (MI) >48 h after the index PCI or clinical-driven target lesion revascularisation. Patient-Oriented Composite Endpoint (POCE) was defined as a composite of all cause mortality, any stroke, any MI and any revascularisation. Spontaneous MI was defined according to Forth universal definition. The event rate was estimated by the Kaplan-Meier method. The event was adjudicated by an independent clinical event committee. Results A total of 208 patients were enrolled in the study. The average anatomical SYNTAX score was 7.96 (±4.6). After procedure, prasugrel monotherapy was immediately initiated. After 3-month, Prasugrel monotherapy was continued in 88.6% up to 1-year. Aspirin monotherapy was prescribed to 10 patients (5.0%), while 6 patients (3.0%) were on DAPT at 1-year. All-cause mortality rate was 1.49%, with no occurrence of cardiovascular death. Revascularisation occurred in 4.0% (n=8) with no occurrence of TLR, while one patient (0.5%) underwent a clinical driven target vessel revascularisation. In summary, 7 out of 8 revascularisations were non-target vessel revascularisation (6 clinically-driven non-TVR). Spontaneous non TV-MI occured in 0.5% (n=1) of patients. There was no definite/probable stent thrombosis up to 1 year. The target lesion related endpoint rate at 1-year was 0%, whereas 1-year POCE rate was 7.0% (n=14). Conclusion Discontinuation of Aspirin and Prasugrel monotherapy at a low maintenance dose of 3.75 mg/day following an angiographically successful stent deployment was feasible and safe in selected patients with CCS and low SYNTAX score. This safety profile is confirmed at 1 year while the investigators, in their large majority and at their own discretion, had maintained the prasugrel treatment.

Altered fibrin clot properties and elevated von Willebrand Factors level are associated with progression to permanent atrial fibrillation during follow-up: a cohort study

Abstract Introduction Little is known about association of prothrombotic markers and atrial fibrillation (AF) progression to permanent arrythmia (PerAF). Formation of denser and poorly lysable fibrin clots have been observed in AF including patients with sinus rhythm in association with stroke and bleeding risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF. Methods In the cohort study, in 226 anticoagulated AF patients (median age 69 years, median CHA2DS2-VASc of 3)with paroxysmal (n=83, 36.7%) or persistent (n=143, 63.3%) arrythmia we assessed at baseline plasma clot permeability (Ks), lysis time (CLT), and fibrinolysis involved proteins, including plasminogen activator inhibitor type 1 (PAI-1) along with von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months. Results PerAF was documented in 62 (27.4%, 5.7%/year) subjects. These patients were older, with larger prevalence of heart failure (HF), higher body mass index by 9.6%, more often presented persistent AF and had longer history of arrythmia by 60%. We observed by 25.7% longer CLT and similar Ks, compared with the remainders, along with higher levels of vWF by 29% and PAI-1 by 21.3%. By multivariable analysis CLT, vWF and HF were independently associated with PerAF (R2=0.697, P<0.001). A cut-off CLT value of ≥105 min had a sensitivity of 88.7% and specificity of 78.7% in prediction of PerAF (area under curve 0.892, 95% confidence interval 0.848-0.935, P<0.001). Conclusion Impaired global fibrinolysis and elevated vWF levels are independently associated with faster progression to PerAF despite anticoagulation.Figure1

Shortened versus standard duration of dual antiplatelet treatment after percutaneous coronary intervention in patients with and without chronic kidney disease: a systematic review and meta-analysis

Abstract Background Impaired renal function is an established risk factor for recurrent cardiac events. The severity of chronic kidney disease (CKD) is related with an increased risk for both ischemic and bleeding complications. As a result, the clinical implications of antithrombotic therapies may be different in patients with CKD as compared to those without. Recently, shortened duration of DAPT, namely one to three months, after percutaneous coronary intervention (PCI) has been proven as a safe and feasible strategy in various different clinical scenarios, like in high-bleeding risk patients, in acute coronary syndromes and complex PCI. However, it remains debatable whether DAPT should be shortened in patients with high ischemic and bleeding risk, such as those with CKD. Purpose The aim of our systematic review and meta-analysis is to explore the safety and efficacy of shortened therapy (1-3 months; S–DAPT) in patients without and without CKD undergoing PCI. Methods Three major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened for eligible randomized – controlled trials, or subgroup or post – hoc analyses of them. The studies should compare shortened (S–DAPT) with longer (>3 months) DAPT (L–DAPT) in patients undergoing PCI, and include data on CKD presence. The endpoints were Net Adverse Clinical Events (NACE) and Major Adverse Cardiac Events (MACE) and should be evaluated at 12 months. NACE and MACE were used as per trial defined. The effect of different DAPT regimens was assessed by calculating the risk ratio (RR) with 95% confidence interval (CI) using random-effects model (Mantel-Haenzel). Results A total of eight studies and 56,660 patients were included in our analysis; a notable proportion of patients (9.7%, N=5,466) suffered from CKD. Our analysis showed an overall benefit of S-DAPT in NACE (RR: 0.88, 95%CI: 0.81 – 0.95), which was consistent in patients with and without CKD (p-interaction=0.58). (Figure 1) No significant difference regarding MACE was observed between S-DAPT and L-DAPT (RR: 0.98, 95%CI: 0.90 – 1.06) in both patients with and without CKD (p-interaction=0.19). (Figure 2) Conclusions Our analysis showed an overall benefit of S-DAPT in NACE without any difference in MACE, with similar findings among patients with and without CKD. Thus, DAPT shortening could be a feasible and safe approach when it is required, even in patients with impaired renal function. Further randomized controlled trials focusing on patients with CKD are required for validating the previous results and exploring further benefits of abbreviated duration of DAPT.Net adverse clinical eventsMajor adverse cardiac events

Real-world implementation of a genotype-guided p2y12-inhibitor de-escalation strategy in acute coronary syndrome patients

Abstract Background CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel, may optimize the balance between ischemic and bleeding risk in ACS patients. Purpose Compare bleeding and ischemic event rates in genotyped patients versus standard care. Methods Since 2015, ACS patients in the FORCE-ACS registry received standard dual antiplatelet therapy (DAPT). Since 2021, immediate genotype-guided P2Y12-inhibitor de-escalation was applied, switching non-carriers of the loss-of-function allele CYP2C19*3 or CYP2C19*2 from ticagrelor or prasugrel to clopidogrel, while loss-of-function carriers, carrying at least one loss-of-function allele, remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction (MI) or stroke and the primary bleeding endpoint, BARC 2, 3, or 5 bleeding, were compared between genotyped those on standard DAPT after one year. Results Among 5,321 enrolled ACS patients, 406 underwent genotyping, compared with 4,915 non-genotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were non-carriers, whereas 34.7% (n=141) were loss-of-function carriers. The primary ischemic endpoint occurred in 5.2% of patients in the genotyped cohort compared to 6.9% in the standard care cohort (adjHR 0.88, 95% CI 0.56–1.38). The rate of the primary bleeding endpoint was lower in the genotyped cohort compared to the standard care cohort (4.7% vs. 9.8%; adjHR 0.50, 95% CI 0.31-0.78). Conclusion These results demonstrate the feasibility of a CYP2C19 genotype-guided P2Y12-inhibitor de-escalation strategy in a real-world ACS population. This strategy reduced bleeding events, while ischemic events were not increased as compared to a standard DAPT regime.Primary ischemic endpointBARC 2, 3 or 5 bleeding

External validation of the CA-AKI score in patients with acute coronary syndrome: A real-world cohort analysis from Asia

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is associated with long-term impairment of kidney function, the need for renal replacement therapy, and subsequent all-cause deaths. A practical risk score, the CA-AKI risk score is derived for the prediction of contrast-associated acute kidney injury. However, this novel score has not received sufficient evidence of external validation in real-world studies, especially in Asian individuals. Methods Short-term endpoints and long-term endpoints were assessed in 8,816 patients with acute coronary syndrome enrolled in a large Asia registry. Discrimination was assessed by Harrell’s C statistic, and calibration was assessed by calibration plots. The ability of the CA-AKI score to predict short-term and long-term prognosis was assessed. Results CA-AKI occurred in 5.3% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. When predicting the risk of CA-AKI, both discrimination and calibration were helpful in model 2 (C-index: 0.72; slope: 0.97) and in model 1(C-index: 0.69; slope: 1.02). The risks of 1-year all-cause mortality and 1-year bleeding were higher in CA-AKI patients (HR: 2.70 [95% CI: 2.22-3.30] and HR: 1.76 [95% CI: 1.41-2.46]; respectively). Conclusion The updated CA-AKI risk score could accurately identify patients with contrast-associated acute kidney injury, the occurrence of which is strongly associated with long-term mortality and bleeding.

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study

Abstract Aims Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective cohort of contemporary ACS patients. Methods SPUM-ACS is a prospective, multicentre study in which ACS patients between 2009 and 2017 were recruited. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE) comprised the secondary endpoints. Results A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p<0.001) and thrombus (60% vs 35%, p<0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower MACE risk (PSM adjusted HR 0.70, 95% CI 0.49-0.99) but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. When including only patients treated with potent P2Y12, the incidence of MACE was not different between the two groups, (log rank p=0.50 and PSM adjusted HR 0.94, 95% CI 0.60-1.48). In the PSM population, GPI use (HR 0.76, 95% CI 0.59-0.99, p=0.04), TIMI 3 at the end of the procedure (HR 0.16, 95% CI 0.08-0.30, p<0.001) and potent P2Y12 inhibitor use (HR 0.70, 95% CI 0.49-0.99, p=0.04) were protective independent predictors of MACE at follow-up, while oral anticoagulation at discharge (4.48, 95% CI 2.10-9.52, p<0.001), multivessel disease (HR 1.95, 95% CI 1.09-3.48, p=0.02) and KILLIP class ≥ 2 at admission (HR 1.98, 95% CI 0.99-3.95, p=0.05) were adverse independent predictors. Conclusion In ACS patients undergoing PCI and broadly treated with potent P2Y12 inhibitors, GPI use reduced the risk of MACE at 1 year, while increasing the risk of major bleedings, with a neutral effect on NACE. The routine use of these pharmacological agents should be discouraged, while in selected patients GPI use should be considered following personalized balancing between ischaemic and bleeding risk.Events in PSM populationEvents in PSM population

Impact of baseline thrombocytopenia on outcomes in hospitalizations for acute coronary syndrome and non-elective percutaneous coronary intervention: meta-analysis

Abstract Background Thrombocytopenia's impact on acute coronary syndromes (ACS) outcomes is poorly understood. A systematic review and meta-analysis aim to elucidate its influence on both short-term and long-term clinical endpoints, guiding tailored management strategies for improved patient care. Methods Our meta-analysis is registered on PROSPERO (CRD42024511832). We conducted a systematic search of PubMed and SCOPUS databases up to February 2024, utilizing keywords to identify studies on ACS or non-elective PCI populations with or without baseline thrombocytopenia (TP) reporting on in-hospital and long-term outcomes. Baseline TP was defined as a platelet count less than 150 x 10⁹/L and had to be established before hospitalization or ACS management or intervention. Binary random effects models were used to estimate pooled unadjusted odds ratios (OR) and 95% confidence intervals (CI). Sensitivity analysis was done by the leave-one-out method, and the heterogeneity was assessed with the I² statistics. Results From 2,831 identified studies, 10 were identified as eligible for inclusion in our pooled analysis and included 6,588,688 patients. Thrombocytopenia was associated with higher risks of in-hospital mortality (OR=1.89, 95% CI:1.55-2.30, p<0.01), in-hospital Major adverse cardiovascular events (MACE) (OR=1.99, 95% CI:1.63-2.43, p<0.01), and in-hospital bleeding (OR=2.62, 95% CI:1.89-3.64, p<0.01). Long-term follow-up revealed increased risks of MACE (OR=1.80, 95% CI 1.49-2.18, p<0.01), bleeding (OR=1.63, 95% CI:1.63-2.25, p<0.01), and cardiovascular mortality (OR=2.07, 95% CI:1.76-2.42, p<0.01) with thrombocytopenia. No significant difference was found in in-hospital stroke outcomes and long-term outcomes for stroke and recurrent myocardial infarction between thrombocytopenic and non-thrombocytopenic groups. Conclusion Thrombocytopenia worsens ACS outcomes. Vigilance and tailored management are crucial for mitigating its impact on patient prognosis. Further research is needed for better interventions.Secondary outcomes forest plot

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Gender and racial differences in outcomes among patients with NVAF treated with oral anticoagulants: a real-world evaluation of Medicare beneficiaries

Abstract Introduction Anticoagulation therapies are essential component of disease management for patients with atrial fibrillation (AF). Direct-acting oral anticoagulants (DOACs), such as apixaban, rivaroxaban, and dabigatran have shown greater benefit in reducing stroke/systemic embolism (SE) and bleeding risk compared to warfarin. However, few studies have assessed whether the beneficial effects of DOACs are consistent across gender and race. Purpose To assess the association between apixaban use and the risk of stroke/SE and major bleeding (MB) compared to warfarin, rivaroxaban, and dabigatran; and to determine whether the associations differ by gender and race. Methods Adult patients with AF diagnosis who initiated warfarin or a DOAC between January 1, 2013 and December 31, 2019 were identified using Medicare claims databases. Patients were classified into warfarin, apixaban, dabigatran, or rivaroxaban cohorts based on index prescription. Inverse Probability Treatment Weighting Cox proportional hazard models were used to assess the association between DOAC therapy initiation and risk of stroke/SE and MB, overall and among gender and race. Results Among a total of 1,079,540 included patients, 486,257 (45.04%) were in the apixaban cohort, 46,920 (4.35%) in the dabigatran cohort, 267,991 (24.82%) in the rivaroxaban cohort, and 278,372 (25.79%) in the warfarin cohort. Overall, the risks of stroke/SE and MB were lower for apixaban when compared with warfarin (stroke/SE: HR: 0.69 [95% confidence interval (CI): 0.65-0.74], MB: 0.59 [95% CI: 0.57-0.60]), rivaroxaban (stroke/SE: 0.88 [95% CI: 0.84-0.92], MB: 0.60 [95% CI: 0.58-0.61]) and dabigatran(stroke/SE: 0.88 [95% CI: 0.80-0.95], MB: 0.76 [95% CI: 0.72-0.80]). Among 140,587 females, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.67-0.78], MB: 0.60 [95% CI: 0.58-0.62]) and rivaroxaban (stroke/SE: 0.88 [95% CI: 0.83-0.93], MB: 0.59 [95% CI: 0.57-0.61]), but similar risk of stroke/SE was noted for apixaban compared to dabigatran (stroke/SE: 0.98 [95% CI: 0.86-1.11]). Among 137,785 males, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. Among 16,288 Black patients, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.63-0.83] MB: 0.59 [95% CI: 0.54-0.65]), also lower risk of MB was noted for apixaban as compared with rivaroxaban (MB: 0.56 [95% CI: 0.5-0.62]), but a similar risk of stroke/SE was noted compared to rivaroxaban and dabigatran, and similar risk of MB was noted compared to dabigatran. Among 247,642 White patients, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. All the results along with comparisons are displayed in the accompanying figures. Conclusion Apixaban demonstrated lower risk of stroke/SE and major bleeding when compared to warfarin, rivaroxaban, and dabigatran across most race and gender subgroups.Figure 1_Risk of stroke/SEFigure 2_Risk of Major Bleeding

Major bleeding complications and antithrombotic treatment after isolated surgical bioprosthetic aortic valve replacement

Abstract Background Despite advancements in surgical techniques and perioperative care, post-operative bleeds and stroke remain significant concerns after bioprosthetic surgical aortic valve replacement (SAVR). Purpose We assessed the incidence of short-term (30d) and long-term major bleeds and strokes and their relations to antithrombotic treatment after isolated bioprosthetic SAVR. Methods The CAREAVR study included 721 patients who underwent isolated SAVR at four Finnish university hospitals between 2002 and 2014. The day-to-day information on short-term antithrombotic treatment was available from a subgroup including 227 patients, of whom 138 (60.7%) had preoperative aspirin. Preoperative aspirin was usually discontinued the day before the index surgery. Enoxaparin 1mg/kg twice daily and vitamin K antagonist (VKA) were routinely initiated on the first postoperative day, and enoxaparin continued until the INR remained at a therapeutic level ≥ 2.0 for two days. The routine duration of VKA treatment after surgery was 3 months. Results The median follow-up time was 4.9 (interquartile range 3.0–7.0) years. During the short-term 30-day period, 31 (4.3%) patients had a major bleed, and 13 (1.8%) patients experienced a major stroke. A vast majority of the bleeding (80.6%) occurred within two days after the surgery, and the tail effect of preoperative aspirin (5-7d) was present in 51.6% of episodes, indicating unintentional triple antithrombotic therapy. During the long-term follow-up (>30d after the index surgery), 40 (5.5%) major bleeding episodes occurred, and 47 (6.5%) patients experienced a major stroke. Overall, 23 (57.5%) of the patients with major bleeding were on OAC during the event. In addition, 13 (27.7%) of the patients experiencing major stroke during the long-term follow-up were on OAC during the event. Conclusions Compared to major strokes, the incidence of perioperative major bleeds was over twofold, the majority occurring during the tail effect of preoperative aspirin. During the long-term follow-up, the risks of stroke and bleeding were equal, and the majority of bleeding episodes appeared during anticoagulation treatment.

Low rates of haemorrhagic stroke, not increased by age, renal/hepatic impairment, concomitant anti-platelet use and high CHA2DS2-VASc scores, in the 4-year follow-up of ETNA-AF-Europe

Abstract Background Balancing the risks of stroke and bleeding is necessary to optimise oral anticoagulation use in clinical practice. Concerns remain over the increased bleeding risk in patients receiving NOACs, and long-term safety data in this population are limited. Purpose To report annualised rates of haemorrhagic stroke in various sub-populations of patients with atrial fibrillation (AF) treated with edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe, a post-authorisation, observational study conducted across 776 sites from 10 European countries, assessed the risks and benefits of edoxaban use in patients with AF. Here, we present the annualised event rates of haemorrhagic stroke during the 4-year follow-up, that occurred overall (on-/off-edoxaban) and on-edoxaban, including sub-populations stratified by age, renal impairment, hepatic impairment, chronic concomitant antiplatelet use and CHA2DS2-VASc score. Patient characteristics were collected at baseline and annualised event rates were reported for outcomes. Results A total of 13,164 patients were included in the full analysis set. Baseline characteristics are reported in Table 1. The overall and on-edoxaban annualised haemorrhagic stroke rates were low (number of events, % [95% confidence interval]: 36, 0.1 [0.05;0.11] and 31, 0.1 [0.05;0.10] respectively). The overall haemorrhagic stroke rates remained low in subgroups stratified by age (<65 years: 4, 0.1 [0.00;0.11]; ≥65–75 years: 13, 0.1 [0.04;0.13]; ≥75 years: 19, 0.1 [0.05;0.12]), renal impairment (yes: 23, 0.1 [0.05;0.13]; no: 12, 0.1 [0.03;0.11]), hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 35, 0.1 [0.06;0.11]), concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.16]; no: 34, 0.1 [0.05;0.11]) and CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 28, 0.1 [0.06;0.12]; high [>4]: 7, 0.1 [0.03;0.18]) (Figure). Likewise, on-edoxaban haemorrhagic stroke rates were low irrespective of age (<65 years: 3, <0.1 [0.00;0.010; ≥65–75 years: 12, 0.1 [0.04;0.13]; ≥75 years: 16, 0.1 [0.04;0.12]); renal impairment (yes: 20, 0.1 [0.05;0.12]; no: 10, 0.1 [0.02;0.10]); hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 30, 0.1 [0.05;0.11]); chronic concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.18; no: 29, 0.1[0.05;0.10]) or CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 25, 0.1 [0.05;0.12]; High [>4]: 6, 0.1 [0.02;0.17]) (Figure). Conclusions The overall and on-edoxaban annualised rates of haemorrhagic stroke were low and were not increased by non-modifiable risk factors such as age, renal/hepatic impairment, concomitant antiplatelet use and high CHA2DS2-VASc scores during the 4-year follow-up. The overall annualised rates on-edoxaban in ETNA-AF-Europe registry are quite comparable with incidence rates reported in the literature in age-stratified populations (incidence/100 person-years: 55-64 years: 0.06 [0.04-0.07]; 65-74 years: 0.1 [0.09-0.1]; 75-84 years 0.2 [0.1-0.2]).Baseline Characteristics

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and outcomes in patients with chronic kidney disease: A report from the APHRS-AF registry

Abstract Background The Atrial Fibrillation Better Care (ABC) pathway is based on three pillars: "A" avoid stroke with oral anticoagulation, "B" better symptoms control, and "C" optimization of cardiovascular risk factors and lifestyles. This integrated approach has been associated with improved outcomes in atrial fibrillation (AF) patients, but few data are available in patients with chronic kidney disease (CKD). Purpose To investigate the correlation between chronic kidney disease, adherence to the ABC pathway, and the occurrence of adverse events in patients with AF enrolled in the Asian-Pacific Heart Rhythm Society-AF Registry. Methods Logistic regression was used to investigate factors associated with CKD, warfarin use and rhythm control strategies. Cox regression analysis adjusted for age≥75 years, paroxysmal AF, CHA2DS2VASc≥2, chronic obstructive pulmonary disease, cancer, and ABC adherence was used to calculate Hazard Ratios (HRs) and 95% Confidence Interval (CI) for the risk of primary outcomes in patients with CKD (eGFR <60 ml/min/1.73m2). Sensitivity analyses were performed in moderate (eGFR 59-30) and severe CKD (eGFR<30). Interaction analysis investigated the effect of ABC pathway based on presence or absence of CKD. Primary outcomes were the risks of all-cause death, major cardiovascular events (MACE: Cardiovascular death, acute coronary syndromes, thromboembolic events, and acute heart failure) and major bleeding. Results We included 2 578 AF patients without CKD (age 66.5±11.3 years, 32.5% females) and 1 047 AF patients with CKD (75.3±10.3 years, 40.8% females). Lower ABC pathway full adherence was observed in CKD patients (42.1% vs 29.5%, p<0.001), primarily due to low adherence to "A" and "C" criteria. Logistic regressions confirmed the lower likelihood of anticoagulation (Odds Ratio (OR) 0.61, 95%CI 0.44-0.83), a higher use of warfarin (OR 1.50, 95%CI 1.23-1.83) and lower use of rhythm control strategies (OR 0.79, 95%CI 0.66-0.94) in CKD patients. After one-year follow up, patients with CKD had a higher incidence of all-cause death (1.6% vs 7.2%, p<0.001) and MACE (3.4% vs 8.1%, p,0.001) compared to those without CKD. On Cox multivariable analysis (Figure 1, Panel A-D), CKD and ABC adherence were independently associated with the risk of all-cause death (HR 2.54, 95%CI 1.69-3.80 and HR 0.57, 95%CI 0.35-0.93, respectively) and MACE (HR 1.58, 95%CI 1.14-2.20 and HR 0.66, 95%CI 0.46-0.95, respectively). The risk of primary outcomes was the highest in those with severe CKD. No association was found with the risk of major bleeding. The interaction analysis confirmed that the beneficial effect of ABC pathway adherence on death (p int= 658) and MACE (p int= 0.568) was irrespective of CKD. Conclusion AF patients with CKD have low ABC pathway adherence and high risk of all-cause death and MACE. Efforts to improve the ABC pathway adherence in AF patients with CKD are needed to improve their long-term clinical outcomes.Figure 1.Cox regression analyses

The association between steroid use and recurrent venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background It is well known that use of oral steroids is a risk factor for development of venous thromboembolism (VTE). However, the impact of use of oral steroids on VTE recurrence has not been fully evaluated in the era of direct oral anticoagulants (DOAC), which has been a clinically relevant issue in the decision-making of anticoagulation strategies for patients who need oral steroids after VTE diagnosis. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with oral steroids after VTE diagnosis in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population were divided into 2 groups according to the use of oral steroids after VTE diagnosis; the steroid group and the non-steroid group. We compared clinical characteristics, management strategies, and outcomes including recurrent VTE, major bleeding and all-cause death, between the 2 groups. Results Patients with steroids and those without accounted for 693 (13%) and 4,504 (87%), respectively. Patients with steroids more often had chronic kidney disease (29% vs. 18%, P<0.001), autoimmune disease (50% vs. 5.4%, P<0.001), thrombocytopenia (7.7% vs 4.9%, P=0.002), and anemia (64.4% vs 54.1%, P<0.001), whereas there was no significant difference in the mean age (68.5 vs. 67.6 years old, P=0.16), the prevalence of women (62% vs 58%, P=0.06), active cancer (30% vs. 29%, P=0.42), and history of VTE (8.4% vs 6.8%, P=0.12) between the 2 groups. The cumulative 5-year incidence of discontinuation of anticoagulation therapy were not significantly different between the 2 groups (61.5% vs. 58.5%, log-rank P=0.16). The cumulative 5-year incidences of recurrent VTE nor major bleeding were not significantly different between the 2 groups (10.4% vs. 9.4%, log-rank P=0.55; 16.9% vs. 13.3%, log-rank P=0.16, respectively). Even after adjusting confounders, the risks of recurrent VTE nor major bleeding were not significantly different (adjusted hazard ratio = 0.97, 95% confidence interval = 0.65-1.45, P = 0.89; adjusted hazard ratio = 1.12, 95% confidence interval = 0.84-1.50, P = 0.44). The cumulative 5-year incidences of all-cause death was significantly different between the 2 groups (44.2% vs. 30.2%, log-rank P<0.001). Even after adjusting confounders, the risk of all-cause death remained significantly different (adjusted hazard ratio = 1.82, 95% confidence interval = 1.56-2.12, P<0.001). Conclusions Use of oral steroids after VTE diagnosis was not significantly associated with an increased risk of VTE recurrence in the DOAC Era, which might suggest that there could be no major concerns on an increased risk of recurrent VTE with oral steroids after VTE diagnosis under appropriate anticoagulation therapy.

Comparison of 600 mg VS 300 mg clopidogrel loading dose for patients with ischemic heart disease: a meta-analysis of randomized controlled trials

Abstract Background While a 600-mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300-mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether a higher clopidogrel LD regimen in primary percutaneous coronary intervention outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease. Purpose The objective of this meta-analysis is to validate current randomized trials that investigate the efficacy and safety of two clopidogrel loading regimens (600 mg vs 300 mg) in patients with ischemic heart disease treated with primary percutaneous coronary intervention. Method A systematic literature search for randomized controlled trials was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects. Result Nine randomized control studies involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only 8 studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced incidence of overall MACE (OR:0.82, 95% CI:0.74-0.91, p=0.0002), nonfatal myocardial infarction (OR:0.56; 95% CI:0.32-0.99, p = 0.15) and target vessel revascularization (OR 0.63; 95% CI 0.41 to 0.95, p = 0.03 ), without significant difference in terms of cardiac death (OR:0.89; 95% CI:0.76-1.04, p=0.15) and stroke (OR 0.92; 95% CI 0.67 to 1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR:1.27; 95% CI:1.08-1.49, p=0.005] without significant difference in minor bleeding (OR:1.05; 95% CI:0.94-1.17, p=0.35). Conclusion The administration of 600 mg of clopidogrel LD reduces the overall risk of MACE with an associated increased risk of major bleeding in patients with ischemic heart disease undergoing primary percutaneous coronary intervention.MACE OUTCOMES

Clinical impact of systemic inflammation across the spectrum of different high-sensitivity CRP values in patients undergoing percutaneous coronary intervention

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.