High Risk Of Bleeding Research Articles

The role of comorbidities for hospital outcome of patients with severe acute pulmonary embolism treated with thrombolytic therapy

Abstract Background The association between the outcome of severe acute pulmonary embolism treated with thrombolytic therapy and the presence of common comorbidities is fairly known. Methodology In this study we investigated the influence of common comorbidities (arterial hypertension, atrial fibrillation, heart failure, coronary disease, diabetes mellitus, active malignant disease, chronic obstructive lung disease, chronic renal failure, anemia and previous stroke) to hospital mortality and the composite of major and clinically relevant non-major bleeding at 7 days from hospital admission in patients with severe acute PE treated with thrombolytic therapy enrolled in the Regional PE Registry from the 4 west-Balkan countries. Univariate and multivariable regression analysis (adjusted to age and the presence of arterial hypotension – systolic blood pressure below 90 mmHg) was used to establish association between comorbidities and hospital outcome of acute PE treated with thrombolysis. Results 2068 patients enrolled with computed tomography pulmonary angiography proven acute, symptomatic PE, and of them 645 patients had features of intermediate-high PE (right ventricle dysfunction with positive biomarkers without severe hypotension) and 283 patients had high-risk PE with arterial hypotension. Of them, 394 (42.5%) were treated with thrombolytic therapy (245 with intermediate-high and 149 with high-risk PE). Overall hospital mortality was 17.0% and the composite of major and clinically relevant non-major bleeding at 7 days was 17.5% (11.2% was major bleeding). Among all tested comorbidities, only 3-staged renal failure (OR 3.56, 95%CI 1.78-7.15, p<0.001 for creatinine clearance 30-59 ml/min compare to clearance ≥ 60 ml/min; and OR 6.01, 95%CI 2.35-15.37, p<0.001 for creatinine clearance <30 ml/min versus ≥ 60 ml/min), and the presence of either paroxysmal or chronic atrial fibrillation had significant higher risk for hospital mortality adjusted to age and the presence of arterial systolic hypotension (OR 2.11, 95% 1.03-4.29, p=0.04). Between all presented comorbidities only the presence of diabetes mellitus type 2 was independently associated with the higher risk for bleeding on thrombolytic therapy OR adjusted to age 2.03, 95%CI 1.126-3.659, p=0.019. Conclusion Creatinine clearance and atrial fibrillation were the independent predictors of hospital death and diabetes mellitus type 2 for bleeding in patients with severe acute PE who were treated with thrombolysis.

Octogenarians, nonagenarians and centenarians with myocardial infarction over time in Sweden

Abstract Background The aim of this study was to evaluate temporal changes in baseline characteristics, in-hospital management and medication at discharge in very elderly with myocardial infarction (MI). Methods Between 2003 and 2016, we included all consecutive patients 80 years or-older, with a MI, included in the nationwide SWEDEHEART registry. The study period was divided into seven equal admission periods. Outcomes included major adverse cardiac and cerebrovascular events (MACCE, including death, MI or stroke) and net adverse cardiac and cerebrovascular events (NACCE, including MACCE and bleeding). All patients had complete 1-year follow up. To evaluate any potential associations between in-hospital management/medications at discharge and clinical outcomes, we adjusted for baseline characteristics and clinical presentation using multivariable Cox regression models. Results We included 85,054 patients. Over time, the proportion of patients with comorbidities such as hypertension, diabetes mellitus, prior percutaneous coronary intervention and a previous bleeding significantly increased but patients were less likely to have a prior MI and previous heart failure (HF). On arrival, the proportion of patients with acute HF declined. Invasive management significantly increased over time as well as prescription of evidence-based medication at discharge. At 1 year, the cumulative rate of MACCE and NACCE significantly decreased. We found a significantly lower risk for death, MI and stroke and a higher risk for bleeding. The observed differences remained significant after adjustment. We found no significant interaction between infarct type and outcomes. Conclusion During the study period, the prognosis in very elderly patients with MI substantially improved. In a population that has been excluded from randomised control trials, implementation of evidence-based management for patients with a MI, seemed to be associated with the lower risk for MACCE and NACCE over time.Cumulative rate of MACCE

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

Cardiac amyloidosis and left atrial appendage closure: a multicenter retrospective study

Abstract Background Thromboembolic stroke risk remains a clinical challenge in cardiac amyloidosis (CA) patients with atrial fibrillation because of the increased prevalence of left atrial appendage thrombi irrespective of CHA2DS2-VASc score and a higher prevalence of factors that increase the risk of bleeding with anticoagulation. Left atrial appendage closure (LAAC) is an effective option in patients with atrial fibrillation and high bleeding risk; however, data describing a LAAC strategy for stroke prevention in patients with CA is limited. Among non-CA patients, procedural success and serious complication rates are around 98% and 3% respectively. Purpose In this multicenter retrospective study, we aimed to investigate whether left atrial appendage closure (LAAC) could reduce the risk of bleeding complications and ischemic cerebrovascular events in patients with CA. Methods In an international multi-center retrospective study, patients with CA that underwent LAAC were included. The diagnosis of CA was established on the basis of histologic confirmation or advanced multimodality cardiac imaging as per current consensus statements. Results A total of 28 patients (93% male; 87% ATTR-CA; 13% AL-CA; mean age 80 years) met inclusion criteria. At baseline, mean CHA2DS2-VASc and HAS-BLED scores were 4 and 3 respectively, mean left ventricular ejection fraction was 50%, and mean indexed left atrial volume was 58 mL/m2. 21% of patients had a prior history of ischemic stroke, 14% prior history of hemorrhagic stroke, 7% prior transient ischemic attack, and 54% had a prior history of major or minor bleeding. Procedural success was achieved in 26 patients (93%) with procedural complications occurring in 2 patients (vascular access site bleeding and cardiac tamponade). Regarding in-hospital and follow-up complications, 0% ischemic stroke, 0% hemorrhagic stroke, and major or minor bleeding in 4% of patients. During follow up, device thrombosis occurred in only 1 patient. Conclusion LAAC is a feasible and effective alternative to anticoagulation in patients with CA and excessive bleeding risk, with procedural success and complication rates similar to reported studies of non-CA patients.

Thirty days clinical outcomes following stent implantation with aspirin-free prasugrel monotherapy in non-ST segment elevation myocardial infarction. Interim report from ASET-Japan pilot study

Abstract Background Dual antiplatelet therapy with a P2Y12 inhibitor, in addition to aspirin, is the standard therapy after percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) to prevent ischemic cardiovascular events. The Acetyl-Salicylic Elimination Trial (ASET) pilot studies conducted in Japan in patients with NSTE-ACS investigated the safety and feasibility of a low-dose prasugrel monotherapy after PCI. Purpose To ensure the safety of the patients, enrolment in the study was implemented only after confirmation of a successful procedure. The abstract reports our interim analysis, aimed at evaluating preliminary safety and feasibility. Methods The ASET-Japan pilot study was designed to explore the feasibility and safety of a low dose of prasugrel monotherapy (3.75mg/day), without adjunctive aspirin, after optimal PCI using Everolimus eluting stent (EES) in Japanese patients with non-ST-segment elevation acute coronary syndromes. The primary endpoint in the ASET-Japan NSTE-ACS (Phase 2) is a 12-month clinical outcome. The study is currently in the follow-up phase. All the target lesions were treated with a platinum-chromium everolimus-eluting stent. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 12-month. If more than 3 events occurred, trial enrollment would have to be terminated by the data and safety monitoring board. Results One hundred one patients were enrolled after successful index PCI and completed a 30 days follow-up. The mean age was 69.1±12.3 years and 75.2% was male. The mean anatomical SYNTAX score was 7.9±4.7. Unstable angina (UAP) and NSTEMI were seen in 24.8% (25/101) and 75.2% (75/101) patients, respectively. According to the Braunwald classification, 8 percent of the patients were categorised as Class IA UAP, 48% as Class IB, 20% as Class IIB, 4% as Class IIIA and 20% as Class IIIB. In NSTEMI patients, the median (IQR) pre-procedural troponin value (cardiac Troponin T or I) was 2.79 (1.12 – 22.27) times the Upper Limit of Normal. According to the PRECISE DAPT score, 36.6% of patients were categorised as High Bleeding Risk (HBR) with scores above 25. At one month, the primary ischemic endpoints of cardiac death, target-vessel spontaneous MI or definite Stent thrombosis did not occur. Two patients (2.0%) had BARC type 3a bleeding. Conclusion Prasugrel monotherapy in the first 30 days following platinum-chromium everolimus-eluting stent deployment is a feasible and safe strategy in NSTE-ACS patients with simple anatomy and successful PCI.

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

Bioprosthetic versus mechanical prostheses in patients aged 50 to 70 years undergoing aortic valve replacement surgery: outcomes analysis from propensity score matching

Abstract Introduction Despite increasing use of bioprosthetic surgical aortic valve replacement (bAVR) in patients ≤70 years [1, 2], the relative benefits compared to mechanical valve replacement (mAVR) remain uncertain [3, 4]. Purpose The current study aims to compare mortality and other important clinical endpoints by prosthesis type for patients aged 50-70 years who received an AVR in a well-characterised Australian cohort. Methods A retrospective cohort study was designed utilising the WAVES Patient Registry and incorporating linked administrative outcome data including all patients who had an AVR in Western Australian public hospitals between 2010-2020. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, separately and combined with non-fatal myocardial infarction and non-fatal stroke (MACE), major bleeding, and days alive and out of hospital (DAOH). Outcomes were compared based on a propensity-matched analysis (including demographics, biometrics, and clinical characteristics). Results Within the initial cohort of 727 patients undergoing surgical AVR (mean age = 63 ± SD 6), a propensity-matched cohort identified 151 patients each with bAVR (mean age = 61 ± 4) and mAVR (mean age = 60 ± 5). Patients who received mAVR versus bAVR had improved all-cause survival (Hazard Ratio [HR] 0.50; 95% CI 0.25-0.99) but increased risk of major bleeding (HR 4.85; 95% CI 1.57-14.98). There were no significant differences in CV mortality (HR 0.58; 95% CI 0.19-1.74), MACE (HR 0.59; 95 % CI 0.32-1.07), or DAOH by prosthesis type (P = 0.452). Conclusions Patients aged 50-70 years who underwent mAVR had lower risk of all-cause mortality compared with bAVR, despite higher bleeding risk. Although risks of CV mortality and MACE were lower in mAVR, statistical significance was not reached, likely due to the small sample size. Larger studies are necessary to confirm these findings, which have important clinical implications.

Short vs Standard Duration Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with New-Generation Drug-Eluting Stents: A Meta- Analysis

Objective: In patients with coronary artery disease, dual antiplatelet therapy (DAPT) is recommended after percutaneous coronaryintervention, but the duration is still debated. This meta-analysis compared short-duration (1 to 3 months) to standard-time (twelve months) double antiplatelet treatment in patients who received coronary intervention with new generation drug eluting Stent.Methodology: To conduct this examination, we methodically looked at PubMed, Cochrane CENTRAL, Embase, and Web of Sciencedatabases for randomized controlled trials, evaluating varying durations of double antiplatelet treatment following new generation stents implantation from July to September 2023. Seven randomized controlled trials were included witha total of 22,945 patients. The primary efficacy endpoint was the incidence of Major adverse cardiovascular events, such as cardiac mortality, heart attack, stent coagulation, and target vessel revascularization; while the safety endpoint was the incidence major bleeding. Secondary endpoints were major adverse cardiovascular and cerebro-vascular complications, any bleeding, and net adverse cardiovascular incidence for a year after stent implantation.Results: Short-time DAPT was linked to a significantly less incidence of major bleeding (0.8% vs 1.5%), any bleeding (2.5% vs 4.2%)and NACE (2.5% vs 4.2%) compared to standard duration of DAPT. No significant variation was noticed among the two groups regarding major adverse cardiovascular events (4.1% vs. 4.2%) and acute cardiovascular and cerebrovascular incidents (4.7% vs. 4.8%). Short-duration DAPT in patients with acute coronary syndrome was linked with decreased risk of bleeding and net adverse cardiovascular events.Conclusion: Short-duration (1- or 3-month) DAPT significantly lowers bleeding risk and reduces net clinical adverse events without increasing ischemic risk, making it a reasonable choice for people with new-generation drug eluting stents, particularly those with highbleeding risk or recent surgery.

Post-PCI anticoagulation with unfractionated heparin in acute coronary syndrome: insight from the STOPDAPT-3 trial

Abstract Background The guidelines recommend the post-procedural anticoagulation should be discontinued after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) except for the specific indications.(1) However, these guideline recommendations were not well supported by data, and therefore, post-PCI parental anticoagulation has been commonly implemented in patients with ACS in the previous studies.(2-5) Purpose To clarify the preference and clinical situations of post-PCI unfractionated heparin (UFH) in ACS patients and to explore the influence of post-PCI UFH on cardiovascular and bleeding outcomes. Methods STOPDAPT-3 trial is a randomized controlled trial to demonstrate the efficacy and safety of the aspirin-free prasugrel monotherapy strategy compared to the conventional dual antiplatelet therapy after PCI in patients with high-bleeding risk or ACS.(6) Data on periprocedural heparin use and its doses were vigorously collected. The current study population was the ACS patients enrolled in the STOPDAPT-3 without use of mechanical circulatory support devices. The two co-primary endpoints were the bleeding outcome defined as the BARC 3 or 5 criteria and the cardiovascular outcome defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Outcomes were assessed at 30 days from index PCI. Results Among 4088 ACS study patients, 2339 (57.2%) patients received post-PCI UFH. Median dose of UFH was 7.1 (IQR 6.0-8.8) units/kg/hour and the median duration was 25 (IQR 24-48) hours. As many as 57.7% of patients received 10000 units/day of heparin after PCI irrespective of body weight. STEMI patients more frequently received post-PCI UFH compared to NSTE-ACS (72.3% and 38.8%, P<0.001) and the patients with intraprocedural adverse angiographic findings such as thrombus, slow-flow, no-reflow, or final TIMI flow <=2 also more frequently received post-PCI UFH than those without (67.6% and 47.5%, P<0.001). Post-PCI UFH was associated with a significantly increased risk of bleeding endpoint (4.75% and 2.52%, adjusted HR 1.69 [95%CI 1.15-2.46], P=0.007) and a numerically increased risk of cardiovascular endpoint (3.16% and 1.72%, adjusted HR 1.56 [95%CI 0.98-2.46], P=0.06). Even in the patients with intraprocedural adverse angiographic findings, post-PCI UFH did not show a clear benefit for cardiovascular endpoint (3.15% and 1.72%, adjusted HR 1.73 [95%CI 0.88-3.41]. P=0.11). Conclusion(s) Post-PCI anticoagulation with UFH was frequently implemented in ACS patients enrolled in the latest large Japanese clinical trial. Post-PCI UFH use was associated with harm in terms of bleeding without a benefit in reducing cardiovascular events.

Respective impact of bleeding and ischemic complications of mortality after percutaneous coronary interventions: substudy from the FRANCE-PCI registry

Abstract Background Patients undergoing percutaneous coronary interventions (PCI) remain at high risk of both bleeding and ischemic events, both burdened with high morbimortality. The respective impact of both type of complications in contemporary PCI, however, remains unclear. Purpose To evaluate and compare the respective impact of ischemic and bleeding complications on mortality after PCI Methods The FRANCE PCI is an ongoing registry of consecutive French patients undergoing PCI and monitored for one year thereafter. Patients presenting with complications after the index PCI were categorized as ischemic complications in case of stent thrombosis, myocardial infarction, stroke or unplanned revascularization, as hemorrhagic complications in case of bleeding BARC ≥3 or as ischemic and hemorrhagic when both types of events occurred in the same patients. The impact of ischemic and hemorrhagic complications on mortality was evaluated separately for the index hospitalization and the 12-months follow-up after hospital discharge, using multivariate logistic model and Cox proportional hazards model, respectively. The multivariate Cox model was developed using complications as time-dependent variables and estimating the hazard ratios (HRs) over 3 periods of time (0 to 8 weeks, 8 to 24 weeks, and 24 to 52 weeks). Consequently, the proportional hazard assumption, tested using the Schoenfeld test, was met for each period. Multiple imputations were performed for missing data on covariates. Results A total of 54,599 patients, with a median age of 69 [60.0-78.0] years, 75.0% male, underwent PCI in 30 centers between 2014 and 2020, in an elective setting for 47% of the cases. During the index hospitalization, an ischemic and hemorrhagic complications occurred in 610 (1.1% 95%CI 1.0-1.2) and 531 (1.0% 95%CI 0.9-1.1) patients, respectively, while the mortality rate was 2.1% 95%CI 2.0-2.2. The association between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality was aOR 8.4 95%CI 6.4-10.9, aOR 10.3 95%CI 8.1-13.2 and aOR 13.2 95%CI 7.0-24.7, respectively. Among the 51,738 patients alive and not lost-to-follow-up after discharge, an ischemic and hemorrhagic complications occurred in 2,727 (5.3% 95%CI 5.1-5.5) and 1,022 (2.0% 95%CI 1.9-2.1) patients, respectively, while the mortality incidence was 3.8% 95%CI 3.6-4.0. The associations between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality according to the periods of time are detailed in Table 1 and Figure 1. Conclusion Both ischemic and hemorrhagic complications after PCI are associated with increased risk of mortality. The risk is particularly increased during the early period after the index PCI and diminishes over time, albeit faster after ischemic complications alone, compared to hemorrhagic events alone or the association of ischemic and hemorrhagic complications.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

The comparison of short-term dual antiplatelet therapy versus standard dual antiplatelet therapy in elderly patients with coronary artery disease who underwent percutaneous coronary intervention

Abstract Introduction Elderly patients are likely to have more underlying risk factors for bleeding and the bleeding risk increases with age although dual anti-platelet therapy (DAPT) is mandatory for patients who underwent percutaneous coronary intervention (PCI) for prevention of ischemic events. Therefore, elderly patients aged 75 or older are included as minor criteria for high bleeding risk, as defined by the Academic Research Consortium for High Bleeding Risk criteria. However, only limited data have been investigated of optimal duration of DAPT for patients aged 75 or older. Purpose The aim of this study is to evaluate optimal DAPT duration for elderly patients aged 75 and older. Methods We selected 1,571 patients aged 75 and older with coronary artery disease (CAD) from the pooled database among the 5 randomized controlled trials related to DAPT duration after PCI. DAPT was consisted of clopidogrel or ticagrelor in addition to aspirin. Short-term DAPT duration was defined as 1 to 3months, and standard DAPT duration was defined as 6 to 12months after PCI. Primary outcomes were net clinical adverse outcomes (NACE), composite of major cardiovascular and cerebrovascular adverse outcomes (MACCE) and TIMI major bleeding at 1 year. The inversed probability of treatment weighting (IPTW) analysis was performed to minimize selection bias effects of pooled database. Results The NACE was not significantly different between the short-term DAPT group (3.9%) and standard DAPT group (7.6%) (HR: 0.69, 95% CI: 0.46-1.04; p=0.076) (Figure A). Moreover, MACCE was not different in both groups. However, the significant reduction of bleeding risk was observed in short-term DAPT group (1.4%) than standard DAPT group (3.4%) (hazard ratio (HR): 0.40, 95% confidential interval (CI): 0.19-0.83; p=0.015) (Figure B). These results were consistent after multivariable Cox regression analysis and IPTW analysis. Conclusions Short-term DAPT duration (1 to 3months) was found to be superior to standard DAPT duration (6 to 12months) in terms of bleeding outcomes without the increased ischemic outcomes in patients aged 75 or older with CAD who underwent PCI.

A prospective study of a novel pocket compression device to reduce pocket hematoma after cardiac implantable electronic device implantation in a high bleeding risk population

Abstract Background Pocket hematoma (PH) is one of the most common complications after cardiovascular implantable electronic device (CIED) implantation resulting in an up to 9 times higher risk for CIED infections.(1) Different preventive strategies have been proposed with mixed results. Current standard of care consists of preventive elastic adhesive tape leaving 2 major disadvantages: unpredictable pressure on the pocket and inability to visually assess the pocket with the bandage applied. Aim To evaluate the safety and effectiveness of a novel pocket compression device in patients undergoing CIED implantation in a high bleeding population. Material and methods This randomized controlled trial included 32 patients in the study group (pocket compression device) and 33 in the control group (elastic adhesive tape). The studied pocket compression device contains an inflatable compartment to modify the degree of pocket compression which is transparent facilitating pocket evaluation. The primary outcome was the incidence of various grades of PH. The secondary outcomes comprised the incidence of pressure lesion, pain score (0-10) and endocarditis during follow-up. Results There were no clinical or procedural differences between groups (age 78.01±9.71, heart failure 53.8%, kidney failure 20.0% and on antithrombotic drugs 49.2%). There were significantly less pocket hematomas in the study group (1/32 (3.1%) vs 20/33 (60.6%), P<0.001). Most pocket hematomas were grade I for which watchful waiting was applied (1/32 (3.1%) vs 17/33 (51.6%), P<0.001). Grade II and grade III PH only occurred in the control group (respectively 1/33 and 2/33) resulting in hospitalization prolongation and longer interruption of antithrombotic drugs >24hours. Two control patients eventually received the study device to control PH. None underwent reoperation. Pressure lesions did not occur. Patients in the study group had lower pain scores at application (0.75±1.12 vs 1.80±1.38, P=0.009), after 2 hours (0.81±1.36 vs 1.94±1.50, P=0.002) and the next day (0.38±0.91 vs 1.06±1.634, P=0.042). None of the patients experienced endocarditis during mean follow-up of 1 year. Conclusion The use of a pocket compression device in patients undergoing CIED implantation in a high bleeding population leads to less PH and postoperative pain in comparison to conventional elastic adhesive tape.bandage study

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.

Efficacy and safety of long-term edoxaban treatment for low body weight cancer patients with isolated distal deep vein thrombosis: a post-hoc subgroup analysis of the ONCO DVT study

Abstract Background Low body weight is known to be a bleeding risk in the anticoagulation treatment. ONCO DVT study revealed that 12-month edoxaban treatment for cancer patients with isolated distal deep vein thrombosis (DVT) reduced a composite outcome of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death compared with 3-month edoxaban treatment. However, the efficacy and safety of long-term edoxaban treatment for cancer patients with low body weight is unclear. Purpose In this subgroup analysis, we assessed the efficacy and safety of 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT. Methods We conducted a post-hoc subgroup analysis of the ONCO DVT study in the low body weight patients. ONCO DVT study was a multicenter, open-label, adjudicator-blinded, randomized clinical trial. Cancer patients with isolated distal DVT were assigned to 12-month or 3-month edoxaban treatment. The primary endpoint was a composite outcome of a symptomatic recurrent VTE or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months. We enrolled patients who met low body weight defined in Japanese Version of High Bleeding Risk criteria (<55 kg for men, <50 kg for women) and evaluated the efficacy and safety of 12-month edoxaban treatment using logistic regression models and log-rank test. Results Among 601 patients in the intention-to-treat population of ONCO DVT study, 322 patients (53.6%) met low body weight: 151 patients were in 12-month edoxaban group and 171 patients were in 3-month edoxaban group. The body weight was similar between two group (47.1±5.2 kg in 12-month edoxaban group vs. 46.9±5.4 kg in 3-month edoxaban group; P=0.77). All of them used a lower dose edoxaban (30 mg once daily) following the dose reduction criteria. 12-month edoxaban group had lower rates of the primary endpoint compared with 3-month edoxaban group (2 patients (1.3%) vs. 10 patients (5.8%); Odds ratio 0.22 [95% CI, 0.05–1.00]; Log-rank P=0.036). There was no significant difference in the major secondary endpoint of major bleeding (12 patients (7.9%) in 12-month edoxaban group vs. 16 patients (9.4%) in 3-month edoxaban group; Odds ratio 0.83 [95% CI, 0.38–1.83]; Log-rank P=0.65). All clinically relevant bleeding events occurred in 22 patients (14.6%) in 12-month edoxaban group and in 27 patients (15.8%) in 3-month edoxaban group (Odds ratio 1.40 [0.90–2.19]; Log rank P=0.13), resulting in the comparable risk of bleeding in the 12-month edoxaban group. Conclusions Our study suggests that 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT prevents recurrent VTE or VTE-related death without increasing the risk of bleeding compared to 3-month edoxaban treatment.primary endpointsecondary endpoint

Clinical implications of hepatorenal function in patients undergoing percutaneous coronary intervention: insights from the SAKURA PCI2 registry

Abstract Background Hepatorenal function is a prognostic predictor for heart failure, cardiac surgery, and transcatheter intervention for structural heart disease. However, the clinical implications of hepatorenal function assessed by the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score is still unclear in patients undergoing percutaneous coronary intervention (PCI). Purpose This study aimed to clarify the association between clinical prognosis and the MELD-XI score. Methods We analyzed 993 patients who underwent PCI from June 2020 to July 2022 in the SAKURA PCI2 registry, a prospective multicenter registry. Patients were stratified into high (>10) or low (≤10) MELD-XI scores. Primary outcome was defined as 2-year major adverse cardio or cerebrovascular event (MACCE), including all-cause death, ischemic stroke, and non-fatal myocardial infarction. Secondary outcome was defined as major bleeding according to the Bleeding Academic Research Consortium 3 or 5. Results Of study participating patients, 253 patients (25.5%) were stratified into a high MELD-XI score group and had a higher prevalence of the high bleeding risk than patients with a low MELD-XI score (92.5% vs. 53.7%, p<0.01). Patients with a high MELD-XI score were associated with MACCE (13.1% vs. 2.7%, p<0.01; adjusted HR 3.78, 95%CI 1.78-8.03, p<0.01) and major bleeding (4.0% vs. 1.3%, p<0.01: unadjusted HR 3.32, 95%CI 1.35-8.18, p=0.01). Moreover, these associations remained consistent in patients with chronic and acute coronary syndrome (MACCE, p for interaction=0.89; major bleeding; p for interaction=0.64). Conclusion A high MELD-XI score was associated with an increased risk of MACCE and major bleeding within two years. Therefore, the MELD-XI score could provide information for risk stratification in patients undergoing PCI.Outcomes

Risk stratification using the academic research consortium high bleeding risk criteria in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Previous studies have reported that the academic research consortium high bleeding risk (ARC-HBR) criteria are useful to predict the risk of bleeding events in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). However, there are few studies investigating the predictive value of the ARC-HBR criteria in patients with atrial fibrillation (AF) undergoing PCI. Purpose The purpose of this study was to investigate whether the ARC-HBR criteria can be applied to long-term risk stratification in patients with AF undergoing PCI. Methods Patients with AF undergoing PCI at 15 institutions between January 2015 and March 2021 were enrolled. The ARC-HBR score was calculated by assigning 1 point for each major criterion and 0.5 points for each minor criterion. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stent thrombosis, and stroke) and major bleeding events (BARC 3 or 5), were evaluated. Results A total of 723 patients were included in this analysis. The best cut-off values of J-HBR score determined by ROC curve analysis to predict MACE and major bleeding events were both 3.0. Of 723 patients, 161 (22.3%) had ARC-HBR score ≥3.0. In Kaplan-Meier curve analyses, the incidence of MACE as well as major bleeding events was significantly higher (log-rank p<0.001 and p=0.010) in patients with ARC-HBR score ≥3.0 compared to those with ARC-HBR score <3 (Figure 1). Conclusion The ARC-HBR score may be useful in assessing the risk of MACE, including thrombotic events, as well as bleeding events in AF patients undergoing PCI.Figure 1

Proton pump inhibitors and cardiovascular risk: a critical review.

Proton pump inhibitors (PPI) are widely used medications for gastrointestinal disorders. Recent research suggests a potential association between long-term PPI use and increased cardiovascular (CV) risk, creating a complex clinical dilemma. This review critically evaluates the current evidence for this association, considering the limitations of observational studies and the lack of definitive confirmation from randomized controlled trials.This review delves into the reported association between PPIs and adverse CV events, examining proposed mechanisms such as drug interactions, electrolyte imbalances induced by PPIs and their potential impact on cardiac and vascular function. Evidence suggests these mechanisms converge, with varying influence depending on patient populations.Clinicians require a risk-benefit analysis for each patient considering their CV risk profile. Alternative gastrointestinal therapies should be explored for high-bleeding risk patients. Medications with lower cytochrome-P450 interaction potential may be preferable among essential PPI users. Elucidating the specific mechanisms by which PPIs might influence CV health, assessing long-term vascular effects and investigating interactions with newer anticoagulant medications are crucial for future research.

Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention.

Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort. The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability. The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Polygenic risk, aspirin and primary prevention of coronary artery disease.

Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk. We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80). The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition.