Higher Risk Of Major Bleeding Research Articles

Resultados clínicos y consumo de recursos tras sustitución valvular aórtica con prótesis biológicas o mecánicas en pacientes de 65 años o más

IntroductionCurrently in Spain, there is a gap in knowledge regarding clinical outcomes and resource utilization in patients aged ≥65years undergoing aortic valve replacement with a bioprosthesis or mechanical prosthesis. MethodsThis is a retrospective study of patients older than 65years, undergoing aortic valve replacement, isolated or in combination with coronary artery bypass grafting between 2003 and 2016. Comparison between types of prosthesis for mortality and major adverse events and were performed in a propensity score matched cohort using competitive risk analysis. Resource utilization was compared with non-parametric tests and multivariant models. Results522 patients were included (348 bioprosthesis, 174 mechanical). At long term, there were no significant differences in mortality (HR=0.848; 95%CI: 0.663-1.086), stroke (HR=1.672; 95%CI: 0.672-4.161) or valve reintervention (HR=0.454; 95%CI: 0.193-1.071). The risk for major bleeding was significantly higher for patients with a mechanical prosthesis (HR=3.171; 95%CI: 1.102-9.123; p=0.032). Regarding in-hospital resource utilization, mechanical prosthesis were associated to a higher consume. ConclusionsIn patients aged ≥65, patients with a mechanical prosthesis were at higher risk for major bleeding at follow-up. Bioprosthesis were associated with a lower in-hospital resource utilization.

Prothrombin Time-International Normalized Ratio Predicts the Outcome of Atrial Fibrillation Patients Taking Rivaroxaban.

Although direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) are considered to be safe, over or under anticoagulation and increased bleeding or thromboembolic risk are still considered individually. We aimed to investigate whether there is an association between prothrombin time and international normalized ratio (PT-INR) or activated partial thromboplastin time (aPTT) ratio, and the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding among AF patients taking rivaroxaban or dabigatran. This multi-center cohort study in Taiwan included 3192 AF patients taking rivaroxaban and 958 patients taking dabigatran for stroke prevention where data about PT-INR and aPTT were available. For patients treated with rivaroxaban, a higher INR level was not associated with a higher risk of major bleeding compared to an INR level < 1.1. The risk of IS/SE was lower for patients having an INR ≥ 1.5 compared to those with an INR < 1.1 (aHR:0.57; [95%CI: 0.37-0.87]; p = 0.01). On-label dosing of rivaroxaban and use of digoxin were independent factors associated with an INR ≥ 1.5 after taking rivaroxaban. For patients taking dabigatran, a higher aPTT ratio was not associated with a higher risk of major bleeding. The risk of IS/SE was lower for patients having an aPTT ratio of 1.1-1.2 and 1.3-1.4 than those with an aPTT ratio < 1.1. In AF patients, rivaroxaban with an INR ≥ 1.5 was associated with a lower risk of IS/SE. PT-INR or aPTT ratios were not associated with bleeding events for rivaroxaban or dabigatran. INR may help predict the outcome of AF patients who take rivaroxaban.

Hyperpolypharmacy is a predictor of mortality after left ventricular assist device (LVAD) implantation

BackgroundThe prevalence of (hyper)polypharmacy in patients on left ventricular assist device (LVAD) support and its effect on clinical outcomeis unknown. Therefore, we aimed to determine the prevalence of (hyper)polypharmacy in LVAD patients and evaluate its association with mortality and complications. Materials and methods210 patients aged ≥40 years who received a primary LVAD implantation between 2011 and 2019 were included for analysis. Polypharmacy and hyperpolypharmacy were defined as the concomitant use of 5–9 and ≥10 medications at discharge after LVAD implantation, respectively. Cause specific cox regression was used to assess the association of ≥10 medications with mortality, cardiac arrhythmia, driveline infection and major bleeding. ResultsThe median age of the patients was 57.5 years, and 35.7 % were female. The average number of discharge medications was 8.8 ± 2.3 per patient. The prevalence of patients with 5–9 medications and ≥10 medications was 62.9 % and 34.8 %, respectively. The median follow-up duration was 948 days (interquartile range 874 days). The prescription of ≥10 medications was significantly associated with a higher risk of mortality (HR 2.03; 95 % CI 1.15–3.6, p-value 0.02) adjusted for sex, age, comorbidity and stratified for device type. The prescription of ≥10 medications was not associated with a higher risk of major bleeding, cardiac arrhythmia or driveline infection. Conclusions(Hyper)polypharmacy is highly prevalent in LVAD patients and is independently associated with a higher risk of mortality. Future research is needed to assess the efficacy of individual risk-benefit profiling of (cardiovascular) medication to ensure appropriate polypharmacy and to decrease negative health outcomes.

The Importance of Early Thrombus Removal

Historically, anticoagulation has been the primary treatment for acute lower extremity deep venous thrombosis (DVT) with or without thrombolysis. Despite large amounts of clinical research data supporting an ‘open vein hypothesis’, which favours early thrombus removal, clinicians have been hesitant to take this option due to a historically high risk of major bleeding and a few notable studies that failed to show any meaningful benefit. The ATTRACT trial failed to show the benefit of using pharmacomechanical catheter-directed thrombolysis (PCDT) for iliofemoral and femoropopliteal DVT but did result in more bleeding. However, the CaVent study before it revealed a significant reduction in post-thrombotic syndrome (PTS) for patients with iliofemoral and femoral DVT after long-term follow-up past 24 months that grew over time. Since these trials, there have been significant advancements in magnetic resonance and CT venography, intravascular ultrasound (IVUS), venous stenting and thrombectomy catheters meaning there is little to no need for adjunct thrombolytics. Results from ongoing research such as CLEAR-DVT reflect the advances in modern technology.

Anticoagulation and/or Antiplatelet in Thrombotic Antiphospholipid Syndrome with Previous Arterial Thromboembolism: A Retrospective Cohort

Introduction: Thrombotic antiphospholipid syndrome (TAPS) is a prothrombotic autoimmune disease associated with a high risk of arterial thromboembolism (ATE). While direct oral anticoagulants (DOAC) are inferior treatment in TAPS with ATE, the optimal antithrombotic regimen of vitamin K antagonists (VKA) and/or antiplatelet therapy (AP) remains unclear. Objectives: To assess the effectiveness and safety of VKA (target (t) international normalized ratio (INR) 2-3), VKA (t INR 2-3) with AP (including dual AP therapy), VKA (t INR >3), VKA (t INR >3) with AP, and AP alone at preventing recurrent thrombotic events in TAPS patients with previous ATE. Methods: This retrospective cohort study included adult TAPS patients with previous ATE assessed at two academic tertiary care centers in Toronto, Canada between April 1, 2011 to April 1, 2021. Included patients met Sydney criteria for TAPS and had a history of ATE (ischemic stroke (IS), transient ischemic attack (TIA), myocardial infarction (MI), or systemic embolism (SE)). At participating centers, patients with a thrombotic history suspicious for TAPS were screened for lupus anticoagulant, anti-cardiolipin antibodies, and/or anti-beta-2-glycoprotein 1 antibodies (anti-B2GP1) at the discretion of the treating physician. Testing for anti-B2GP1 was only available as a send away test. We excluded patients with a known cardioembolic source for their ATE including atrial fibrillation, patent foramen ovale, mechanical heart valves, Libman-Sacks endocarditis, those with initial ATE associated with catastrophic antiphospholipid syndrome (CAPS), and those treated with DOAC. Outcomes included both thrombotic and bleeding events. Recurrent thrombosis included both ATE and VTE. ATE included IS, TIA, MI, or SE. Bleeding events were categorized as major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) as defined by International Society on Thrombosis and Haemostasis criteria. Outcomes were assessed during the time the particular antithrombotic regimen was used. If a single patient had multiple antithrombotic regimens, they were included in multiple groups for the time they used that particular antithrombotic regimen, defined as antithrombotic trials. Outcomes were calculated as the number of events per 100 patient years by antithrombotic regimen with 95% confidence intervals (CI) using Poisson's exact test. Statistical calculations were performed using SPSS. Results: From an initial 891 patients with at least one positive antiphospholipid antibody test, 120 patients met criteria for TAPS and had a previous ATE. 62 patients were excluded for the following reasons: 47 for a cardio-embolic source of ATE, 5 for absence of any follow up, 7 for use of DOAC, and 3 for CAPS in the absence of any other ATE. After exclusions, 58 patients with a total of 89 antithrombotic trials were included in the analysis with a cumulative follow up of 248.4 years. The study population comprised of thirty-one (53.4%) women with a mean age of 51 (Standard Deviation (SD) 12.9) years at the start of their initial antithrombotic trial. Twenty-three (39.7%) patients were known to have systemic lupus erythematosus (SLE) whereas seven (12.1%) patients had non-SLE autoimmune disorders. Thirty-four (58.6%) patients had baseline hypertension. The baseline characteristics are summarized in table 1. Overall, there were a total of 7 ATE and 1 VTE recurrences with a thrombotic rate of 3.2 per 100 patient-years (95% CI 1.4 to 6.3). The recurrence rates in the VKA (t INR 2-3), VKA (t INR 2-3) with AP, VKA (t INR >3) with AP, and AP alone were 3.3 (95% CI 0.9 to 8.4), 2.6 (95% CI 0.3 to 9.3), 0 (95% CI 0 to 18.8), and 6.8 (0.8 to 24.4) per 100 patient-years respectively. There were a total of 10 MB events including 4 intracranial bleeding (ICB), 1 gastrointestinal bleeding, and 5 other types of MB. ICB occurred in 3 patients on VKA (t INR 2-3) and 1 on VKA (t INR 2-3) with AP. Outcomes are summarized in table 2. Conclusions: This retrospective cohort of 58 patients with TAPS and a previous ATE demonstrated a numerically higher risk of recurrent thrombosis with AP alone and a numerically higher risk of MB with the combination VKA and AP. Study limitations include the small sample size, risk of selection bias, and retrospective design. Larger, prospective studies are needed to confirm our observations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association of intravenous heparin administration with in-hospital clinical outcomes among hospitalized patients with acute heart failure

BackgroundsPatients with acute heart failure (AHF) possess a high risk for thromboembolism, and thromboembolism prophylaxis using heparin has been recommended by the guidelines. MethodsAmong 4056 patients enrolled in the KCHF Registry, the current study population consisted of 2525 patients after excluding patients with acute coronary syndrome and oral anticoagulants on admission and those with mechanical circulatory supports. There were 789 patients (31%) with heparin administration within 24 h after admission, and 1736 patients (69%) without. ResultsThe baseline characteristics included mean age: 78 ± 13 years, New York Heart Association class IV: 51%, ischemic etiology: 30%, atrial fibrillation: 31% and mean left ventricular ejection fraction: 45%. During median hospitalization length of 16 days, 161 patients had all-cause death, 34 patients developed ischemic stroke, and 48 patients developed major bleeding. Multivariable logistic regression analyses demonstrated that heparin administration compared with no heparin administration was not associated with a lower risk for all-cause death (OR: 1.39, 95%CI: 0.90–2.15; P = 0.14), nor for ischemic stroke (OR: 1.14, 95%CI: 0.53–2.43; P = 0.74), but was associated with a higher risk for major bleeding (OR: 2.88, 95%CI: 1.54–5.41; P < 0.001). ConclusionsIn patients with AHF, heparin administration within 24 h after admission was not associated with a lower risk of all-cause death and ischemic stroke, but was associated with a higher risk of major bleeding during hospitalization. Our study raises questions about the routine use of heparin for thromboembolism prophylaxis in hospitalized patients with AHF. Further studies are warranted to address the utility of anticoagulant therapy in these patients.

Abstract 10549: American Heart Association's Life's Simple 7 and Major Bleeding in Atrial Fibrillation: A Multicenter Cohort Study

Background: Stroke prevention with oral anticoagulation (OAC) is a mainstay therapy in atrial fibrillation (AF) but is associated with increased bleeding. Identifying health determinants that contribute to this risk is essential to minimizing these adverse events and evaluating the risk benefit of OAC in an individual patient. This study examines the association between the seven cardiovascular risk factors (blood pressure, cholesterol, smoking status, physical activity, glucose, BMI, and diet) from the American Heart Association’s (AHA) Life’s Simple 7 (LS7) and major bleeding in older individuals with AF on OAC. Methods: In this multicenter prospective cohort study, we enrolled 1064 patients who were 65 years old and above, had non-valvular AF, and on OAC and followed them for 2 years. Based on AHA’s LS7 criteria, each risk factor was graded on a 3-point scale: 0 points (poor), 1 point (intermediate), and 2 points (ideal). Patients were separated into poor (0-6 pts), intermediate (7-9 pts), or ideal (10-14 pts) cohorts based on their aggregate score. Cox models were used to assess the relationship between the aggregate cohort scores and major bleeding as well as each individual cardiovascular risk factor score and major bleeding. Results: Our 1064 patients were separated into poor (n=242), intermediate (n=581) and ideal (n=241) cardiovascular health cohorts. There was a total of 95 major bleeding events, 8.93% of patients who had a major bleed, and a crude rate of 4.68 major bleeding events per 100 person-years. Compared to the ideal group, patients in the poor (HR, 2.29; 95% CI, 1.13 to 4.65) and intermediate groups (HR, 2.17; 95% CI, 1.14 to 4.14) were more likely to have a major bleeding event. Additionally, patients with poor smoking status (HR, 2.78; 95% CI, 1.29 to 5.98) or physical activity (HR, 1.66; 95% CI, 1.07 to 2.59) were significantly more likely to have a major bleeding event than those in the intermediate and ideal categories. Conclusions: In older adults with AF on OAC, poor cardiovascular health, smoking, and poor physical activity are all associated with a higher risk of major bleeding. Further investigation is needed to determine if smoking cessation and physical activity can lead to clinically meaningful reduction in bleeding events.

Performance of the ABC-bleeding risk score for assessing major bleeding risk in Chinese patients with atrial fibrillation on oral anticoagulation therapy: A real-world study.

To evaluate performance of the ABC (Age, Biomarkers, Clinical history)-bleeding risk score in estimating major bleeding risk in Chinese patients with atrial fibrillation (AF) on oral anticoagulation (OAC) therapy in real-world practice. Data were collected from the Chinese Atrial Fibrillation Registry study (CAFR). Patients were stratified into low-, medium-, and high-risk groups based on ABC-bleeding risk score with 1-year major bleeding risk (<1%, 1-2%, and > 2%) and modified HAS-BLED score (≤1, 2, and > 2 points). Cox proportional-hazards (Cox-PH) models were used to determine the association of major bleeding incidence with bleeding scores. Harrell's C-index of the two scores were compared. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) at 1 year were employed to evaluate the reclassification capacity. The calibration curve was plotted to compare the predicted major bleeding risk using ABC-bleeding risk score with the observed annualized event rate. The decision analysis curves (DCA) were performed to show the clinical utilization of two scores in identifying major bleeding events. The study included 2,892 AF patients on OAC therapy. After the follow-up of 3.0 years, 48 patients had major bleeding events; the incidence of a bleeding event in the low-, medium-, and high-risk groups according to ABC-bleeding risk score was 0.31% (reference group, HR = 1.00),0.51% (HR = 1.83, 95%CI: 0.91-3.69, P = 0.09), and 1.49% (HR = 4.92, 95%CI: 2.34-10.30, P < 0.001), respectively. Major bleeding incidence had an independent association with growth differentiation factor 15 (GDF-15) level (HR = 2.16, 95%CI: 1.27-3.68, P = 0.005) after adjusting components of the HAS-BLED score and cTnT-hs level. The ABC-bleeding score showed a Harrell's C-index of 0.67 (95%CI: 0.60-0.75) in estimating major bleeding risk, which was non-significant compared to the modified HAS-BLED score (0.67 vs. 0.63; P = 0.38). NRI and IDI also revealed comparable reclassification capacity of ABC-bleeding risk score compared with HAS-BLED score (14.6%, 95%CI: -10.2%, 39.4%, P = 0.25; 0.2%, 95%CI -0.1 to 0.9%, P = 0.64). Cross-tabulation of the two scores showed that the ABC-bleeding score outperformed the HAS-BLED score in identifying patients with a high risk of major bleeding. The calibration curve showed that the ABC-bleeding risk score overestimated the observed major bleeding risk. DCA did not show any difference in net benefit when using either of the scores. This study verified the value of the ABC-bleeding risk score in assessing major bleeding risk in Chinese patients with AF on OAC therapy in real-world practice. Despite the overestimation of major bleeding risk, ABC-bleeding score performed better in stratifying patients with a high risk than the modified HAS-BLED score. Combining the two scores could be a clinically practical strategy for precisely stratifying AF patients, especially those at a high risk of major bleeding, and further supporting the optimization of OAC treatment.

Impact of the risk of malnutrition on bleeding, mortality, and ischemic events in patients with acute myocardial infarction

Background & aimsData regarding the relationship between malnutrition and clinical outcomes of acute myocardial infarction (AMI) is limited. The study aims to evaluate the clinical impact of malnutrition in AMI patients after percutaneous coronary intervention (PCI). Methods and resultsThe COREA-AMI registries identified 10,161 AMI patients who underwent PCI from January 2004 to August 2014. Patients with geriatric nutritional risk index (GNRI) scores of <82, 82 to <92, 92 to <98, and ≥98 were categorized as having severe, moderate, mild malnutrition risk, and absence of risk, respectively. Associations of GNRI with Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding, all-cause death, and major cardiovascular events (MACEs; a composite of cardiovascular death, myocardial infarction, or ischemic stroke) were evaluated. Over 50% of AMI patients were malnourished, with 25.0%, 22.7%, and 4.9% having mild, moderate, and severe malnutrition risks, respectively. Over a median 4.9-year follow-up, patients with malnutrition risk had higher risks of BARC 3 or 5 bleeding (adjusted hazard ratios [aHRs], 1.27, 1.55, and 2.02 for mild, moderate, and severe, respectively; p < 0.001), all-cause death (aHRs, 1.26, 1.46, and 1.85 for mild, moderate, and severe, respectively; p < 0.001), and MACEs (aHRs, 1.14, 1.32, and 1.67 for mild, moderate, and severe, respectively; p < 0.001) than patients without risk. ConclusionElevated malnutrition risk was common among AMI patients undergoing PCI and was strongly associated with a higher risk of major bleeding, all-cause death, and major ischemic events.

Revascularization of significant coronary artery disease in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis

Abstract Background The prevalence of coronary artery disease (CAD) in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI) is high. However, the importance of a percutaneous coronary intervention (PCI) prior to TAVI has been matter of debate. Importantly, patients undergoing TAVI are characterized by high age often accompanied by highly calcified coronary arteries, increasing the risk of severe periprocedural complications. Moreover, patients with a severe aortic valve stenosis are limited in their ability to compensate for these life-threatening complications. Together with the necessity of dual antiplatelet therapy after PCI, this may explain a possible negative effect of PCI in this patient population. However, there is still insufficient evidence regarding the importance of PCI in patients undergoing TAVI. Purpose The aim of this systematic review and meta-analysis was to assess the need for PCI in patients with significant CAD undergoing TAVI. Methods A systematic search was conducted to identify studies comparing optimal medical treatment only versus PCI in patients with significant CAD undergoing TAVI. Endpoints were all-cause mortality, cardiac death, stroke, myocardial infarction, and major bleeding which were assessed at 30 days, one year, and beyond one year following TAVI. Results A total of 14 studies was included in this meta-analysis, including 3838 patients of which 1806 patients (47.1%) underwent PCI before TAVI. All-cause mortality was not significantly different between optimal medical treatment only and PCI at 30 days (OR: 1.27; 95% CI, 0.91–1.77; p=0.17; I2=0%), at one year (OR: 0.91; 95% CI, 0.64–1.29; p=0.59; I2=45%), and beyond one year (OR 0.68; 95% CI, 0.42–1.08; p=0.10; I2=49%). Cardiac death and myocardial infarction was similar across the groups at 30 days (OR cardiac death: 1.94; 95% CI, 0.36–10.56; p=0.45; I2=28%; OR myocardial infarction: 0.50; 95% CI, 0.13–1.91; p=0.31; I2=0%), and at one year (OR cardiac death: 0.77; 95% CI, 0.19–3.13; p=0.72; I2=84%; OR myocardial infarction: 0.74; 95% CI, 0.21–2.66; p=0.64; I2=18%). Stroke did not significantly differ between PCI and optimal medical treatment groups at 30 days (OR: 0.77; 95% CI, 0.31–1.92; p=0.57; I2=0%). However, patients that underwent TAVI without preceding PCI had significantly lower risk of major bleeding at 30 days (OR: 0.66; 95% CI, 0.46–0.94; p=0.022; I2=0%). Conclusion This systematic review and meta-analysis showed no significant differences in clinical outcomes between patients with and without PCI prior to TAVI at both short- and long-term follow-up, apart from a higher risk of major bleeding within 30 days in patients undergoing PCI before TAVI. Funding Acknowledgement Type of funding sources: None.

Multimorbidity, frailty and malnutrition: moving beyond traditional risk factors for risk assessment in atrial fibrillation. The Murcia Atrial Fibrillation Project II

Abstract Background The management of atrial fibrillation (AF) has evolved over the last decade with a more towards a more multidisciplinary, integrated and holistic approach. However, several conditions that may influence the prognosis and management of AF patients are still under-recognised. Purpose Our aim was to investigate if multimorbidity, frailty and malnutrition are associated with the risk of worse clinical outcomes in patients with recent diagnosis of AF starting oral anticoagulation (OAC) therapy. Methods Prospective cohort study including outpatients newly diagnosed with AF starting vitamin K antagonist (VKA) therapy from July 1, 2016 to June 30, 2018. Morbidity was assessed with the crude number of comorbidities. Frailty was assessed with the Clinical Frailty Scale (CFS). Nutrition status was assessed with the Controlling Nutritional Status (CONUT) score. During 2-years of follow-up, we recorded all ischemic strokes/transient ischemic attacks (TIAs), major bleeds (according to the 2005 International Society on Thrombosis and Haemostasis criteria), and all-cause deaths. Results We included 1050 patients (540 [51.4%] females, median age 77 [IQR 70–83] years), with median CHA2DS2-VASc of 4 [IQR 3–5] and median HAS-BLED of 2 [IQR 2–3]. The median crude number of comorbidities was 3 [IQR 2–5], whereas the median CFS and CONUT score were 2 [IQR 2–3] and 2 [IQR 1–3], respectively. The crude number of comorbidities, CFS and CONUT score demonstrated a significant positive correlation (p&amp;lt;0.001 for all correlations). After adjusting for several risk factors (age, sex, hypertension, diabetes, previous stroke, vascular disease, heart failure, chronic kidney disease, dyslipidemia, sleep apnoea, hepatic disease, and cancer), the CFS was independently associated with major bleeding (adjusted HR 1.25, 95% CI 1.07–1.45) and all-cause mortality (aHR 1.20, 95% CI 1.09–1.32). The crude number of comorbidities (aHR 1.30, 95% CI 1.14–1.49) was also associated with major bleeding, and the CONUT score (aHR 1.25, 95% CI 1.15–1.35) was associated with all-cause mortality. Any frailty degree (i.e CFS ≥5) was associated with a 3-fold higher risk of major bleeding (aHR 3.04, 95% CI 1.67–5.52) and a 2-fold higher risk of death (aHR 2.04, 95% CI 1.39–3.01), whereas the moderate/severe malnutrition (i.e. CONUT ≥5) was an independent risk factor for ischemic stroke/TIA and (aHR 2.25, 95% CI 1.11–4.56) and death (aHR 3.21, 95% CI 2.14–4.83) (Figures 1 and 2). Conclusions Frailty and malnutrition are important risk factors for bleeding, stroke and mortality in AF. The frailty degree and nutritional status should be assessed in all AF patients in order to address them properly and provide a truly integrated management. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, through the Instituto de Salud Carlos III after independent peer review (research grant: PI17/01375 co-financed by the European Regional Development Fund)

Comparison between ticagrelor and clopidogrel in high bleeding risk patients with acute coronary syndrome

Abstract Background Potent antiplatelet agents such as ticagrelor are associated with a lower risk of ischemic events than clopidogrel in patients with acute coronary syndrome (ACS). However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in individuals who have a high bleeding risk (HBR). This study aimed to assess treatment outcomes following dual antiplatelet therapy (DAPT) using either ticagrelor or clopidogrel in ACS patients with HBR. Methods All HBR patients enrolled in the SWEDEHEART registry who were discharged with DAPT using ticagrelor or clopidogrel following ACS between 2010 and 2017 were included in this study. Bleeding risk was assessed using the 4-item PRECISE-DAPT score, which consists of age, prior bleeding, haemoglobin concentration and creatinine clearance. HBR was defined as a PRECISE-DAPT score ≥25. Inverse-probability of treatment weighting was used to adjust for baseline differences between the treatment groups. The main analysis consisted of a doubly robust estimation of causal effect using Cox proportional hazards models. Data on major bleeding, recurrent myocardial infarction (MI), ischemic stroke and all-cause mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, ischemic stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and major bleeding. Results Of all ACS patients, 36% (n=25,042) had a PRECISE-DAPT score ≥25. Approximately half of the study participants were treated with ticagrelor (n=11,848). Ticagrelor reduced the risk of MI (hazard ratio [HR], 0.82 [95% CI 0.74–0.91]), ischemic stroke (HR, 0.73 [95% CI 0.60–0.88]) and MACE (HR, 0.90 [95% CI 0.84–0.97]), while also increasing the risk of major bleeding compared to clopidogrel (HR, 1.30 [95% CI 1.16–1.47]). We found no significant differences in all-cause mortality (HR 1.02 [95% CI 0.92–1.12]) and NACE (HR 0.98 [95% CI 0.92–1.05]). Conclusions Ticagrelor was associated with a lower risk of recurrent ischemic events, but a higher risk of major bleeding compared to clopidogrel. There were no significant differences in all-cause mortality and NACE between the treatment groups. These results suggest that more potent antiplatelet agents might not be superior to clopidogrel in ACS patients with HBR. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Stockholm county council

Bleeding outcomes with ticagrelor versus clopidogrel in patients with acute coronary syndrome; a focused analysis from the multicenter CREA ARIAM Andalucia registry

Abstract Background/Introduction With the advent of more potent antithrombotic agents, bleeding has emerged as an important safety concern in patients with acute coronary syndrome (ACS). Moreover, hemorrhagic complications have been strongly linked with subsequent mortality in this clinical scenario. Purpose We sought to determine the incidence, types, timing and prognostic relevance of major bleeding events in ACS patients treated with ticagrelor or clopidogrel in contemporary practice. Methods Prospective, observational, multicentre all-comers registry of ACS patients who were intended to receive a 12-month DAPT course with ticagrelor or clopidogrel. Major bleeding was defined as a type 3 or 5 bleed using the Bleeding Academic Research Consortium (BARC) definition. Bleeding was further classified according to the anatomic location. All bleeding episodes were analysed accounting for death as a competing event, using competing risk regression models based on the on-treatment principle (i.e., according to the P2Y12 inhibitor actually received from date of index admission until either time of DAPT cessation plus 14 days or censoring, whichever occurred first). Results Among 2070 patients surviving to hospital discharge (mean age 63 years, 27% women, 62.5% STEMI), 106 (5.3%, 0.6%/year) experienced major bleeding event at a median time of 92 days (interquartile range, 6–187 days) after discharge. Most events (n=59, 55.7%) were BARC type 3a bleeds with 2 fatal bleeds (type 5b). In most cases (53%), the site of bleeding was gastrointestinal, followed by intracranial (n=13, 12%). After adjustments for baseline predictors, ticagrelor was associated with increased but not statistically significant risk of major bleeding compared with clopidogrel (5.6% vs 5.2%, adjusted hazard ratio [aHR] 1.40, 95% CI 0.96–2.05; P=0.075). Major bleeding was significantly associated with nearly 2-fold higher risk of mortality (aHR 1.94; 95% CI 1.32–2.86; P=0.001), irrespective of P2Y12 inhibitor treatment (P interaction = 0.159). Conclusion(s) Bleeding was not rare within 1 year after index ACS, with incidence rates peaked at 30 to 60 days post-index admission. The most common bleeding site was gastrointestinal followed by intracranial haemorrhage. Ticagrelor use was not associated with significantly increased risk of major bleeding compared with clopidogrel whereas bleeding led to a nearly 2-fold higher risk of major bleeding. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Astra-Zeneca

Percutaneous Left Atrial Appendage Occlusion in Comparison to Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Atrial Fibrillation.

Background This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation. Methods and Results Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non-vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all-cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow-up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84-1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81-1.41]), and intracranial bleeding (HR, 1.08 [0.72-1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05-1.42], P=0.01) and a lower risk of mortality (HR, 0.73 [0.64-0.84], P<0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding. Conclusions In comparison to non-vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

Efficacy and safety of vitamin-K antagonists and direct oral anticoagulants for stroke prevention in patients with heart failure and sinus rhythm: An updated systematic review and meta-analysis of randomized clinical trials.

Heart failure (HF) is a major public health issue associated with significantly increased risk of stroke. It remains uncertain whether oral anticoagulation (OAC) in patients with heart failure and sinus rhythm (HF-SR) could improve prognosis. We performed a systematic search of PubMed and Embase databases for randomized controlled clinical trials assessing oral anticoagulants versus antiplatelets or placebo in patients with HF or ventricular dysfunction/cardiomyopathy without clinical HF and SR. The outcomes assessed were stroke/systemic embolism, major bleeding, myocardial infarction, all-cause mortality, and HF hospitalization. Seven trials of 15,794 patients were eligible for our analyses. The overall follow-up duration was 32,367 patient-years corresponding to a mean follow-up of 2.05 years per patient. Four trials included patients treated with warfarin and three included patients treated with rivaroxaban. OAC was associated with reduced rate of stroke or systemic embolism compared to control (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.44, 0.73, number needed to treat (NNT): 71.9) but higher rate of major bleeding (OR: 1.92, 95% CI: 1.47, 2.50, number needed to harm (NNH): 57.1). In the subgroup analysis according to the type of OAC, rivaroxaban was associated with significantly reduced rate of stroke or systemic embolism (1.24 vs 1.97 events per 100 patient-years, respectively, OR: 0.63, 95% CI: 0.45, 0.88, NNT: 82) and higher risk of major bleeding (OR: 1.66, 95% CI: 1.26, 2.20) compared to antiplatelets or placebo. There was no significant differences between groups for the outcomes of myocardial infarction, all-cause mortality, and HF hospitalization. This analysis shows that any benefit of OAC for stroke prevention may be offset by an increased risk of major bleeding in HF-SR patients. A well-designed randomized controlled trial of newer safer OACs is needed in this population.

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis

IntroductionDirect oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4–20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH). Materials and methodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses. ResultsSeven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47–0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77–2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17–2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11–1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk. ConclusionsCompared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events.

Hemorrhage Risk Among Patients With Breast Cancer Receiving Concurrent Direct Oral Anticoagulants With Tamoxifen vs Aromatase Inhibitors

Tamoxifen is commonly used as adjuvant therapy in breast cancer and is proposed to interfere with cytochrome P450 enzyme and P-glycoprotein pathways. Concurrent use with direct oral anticoagulants (DOACs) poses the threat of a potentially dangerous drug-drug interaction by leading to an increase in hemorrhage risk. To assess the risk of hemorrhage in patients with breast cancer coprescribed a DOAC and tamoxifen compared with a DOAC and an aromatase inhibitor (AI). This population-based, retrospective cohort study was conducted among adults aged 66 years or older who were prescribed tamoxifen (compared with an AI) concurrently with a DOAC in Ontario, Canada, between June 23, 2009, and November 30, 2020, and followed up until December 31, 2020. Concurrent prescription of a DOAC and tamoxifen compared with a DOAC and an AI. The primary outcome was major hemorrhage requiring an emergency department visit or hospitalization after prescription. Overlap weighted Cox proportional hazards models, accounting for multiple covariates, were used to assess the association between hemorrhage and tamoxifen or AI use with a DOAC. Among a total of 4753 patients (4679 [98.4%] women; mean [SD] age, 77.4 [7.4] years), 1179 (24.8%) were prescribed tamoxifen, and 3574 (75.2%) were prescribed an AI. Rivaroxaban (2530 [53.2%]) and apixaban (1665 [35.0%]) were the most frequently used DOACs. Patients taking AIs were younger than patients taking tamoxifen (mean [SD] age, 77.1 [7.3] vs 78.3 [7.6] years), with higher Charlson Comorbidity Index (mean [SD], 1.8 [2.4] vs 1.5 [2.2]) and more advanced cancer stage (stages III and IV, 569 [15.9%] vs 127 [10.8%]). During a median follow-up of 166 days (IQR, 111-527 days), tamoxifen was not associated with a higher risk of major hemorrhage (29 of 1179 [2.5%]) compared with an AI (119 of 3574 [3.3%]) when combined with a DOAC (absolute risk difference, -0.8%; weighted hazard ratio, 0.68 [95% CI, 0.44-1.06]). These results were similar in additional analyses using a more liberal definition of hemorrhage, accounting for kidney function, limiting follow-up to 90 days, stratifying by incident and prevalent DOAC users, and accounting for cancer duration and the competing risk of death. In this cohort study, findings suggest that among DOAC users, the concurrent use of tamoxifen was not associated with a higher risk of hemorrhage compared with the concurrent use of an AI. These findings should directly inform prescribers regarding the apparent safety of concurrent DOAC and tamoxifen use.

Mechanical circulatory support devices for elective percutaneous coronary interventions: novel insights from the Japanese nationwide J-PCI registry.

AimsWe examined in-hospital outcomes of patients that required mechanical circulatory support (MCS), such as intra-aortic balloon pumping (IABP), Impella®, or veno-arterial extracorporeal membrane oxygenation (VA-ECMO), for elective percutaneous coronary interventions (PCIs).Methods and resultsThe J-PCI is a prospective Japanese nationwide multicentre registry sponsored by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) and designed to collect clinical variables and in-hospital outcome data on consecutive patients undergoing PCI. Of the 253 228 patients registered between January 2018 and December 2018, 1627 patients (0.6%) undergoing elective PCI under MCS at 551 sites were analyzed. The mean age of the patients was 74 years, and 25.2% of the patients were females. Multivessel disease and left main disease were observed in 59.0% and 19.7% of the patients, respectively. Majority of patients were treated with IABP alone (86.2%), followed by IABP plus VA-ECMO (6.0%) and Impella alone (3.9%). In-hospital mortality was reported in 134 patients (8.2%). Cardiac death was more common than non-cardiac death (6.8% vs. 1.5%). About 34.6% of the patients receiving VA-ECMO died during hospitalization, whereas 7.2% and 5.3% of patients receiving Impella and IABP died, respectively (P < 0.01). The proportion of patients with VA-ECMO or Impella who had major bleeding requiring blood transfusion was higher than that of patients with IABP (14.1% vs. 13.0% vs. 2.8%).ConclusionIn the setting of elective PCI, in-hospital mortality of patients requiring MCS was considerably high. VA-ECMO or Impella was associated with a higher risk of major bleeding than IABP.

Predicting major bleeding during extended anticoagulation for unprovoked or weakly provoked venous thromboembolism

AbstractNo clinical prediction model has been specifically developed or validated to identify patients with unprovoked venous thromboembolism (VTE) who are at high risk of major bleeding during extended anticoagulation. In a prospective multinational cohort study of patients with unprovoked VTE receiving extended anticoagulation after completing ≥3 months of initial treatment, we derived a new clinical prediction model using a multivariable Cox regression model based on 22 prespecified candidate predictors for the primary outcome of major bleeding. This model was then compared with modified versions of 5 existing clinical scores. A total of 118 major bleeding events occurred in 2516 patients (annual risk, 1.7%; 95% confidence interval [CI], 1.4-2.1). The incidences of major bleeding events per 100 person-years in high-risk and non–high-risk patients, respectively, were 3.9 (95% CI, 3.0-5.1) and 1.1 (0.8-1.4) using the newly derived creatinine, hemoglobin, age, and use of antiplatelet agent (CHAP) model; 3.3 (2.6-4.1) and 1.0 (0.7-1.3) using modified ACCP score, 5.3 (0.6-19.2) and 1.7 (1.4-2.0) using modified RIETE score, 3.1 (2.3-3.9) and 1.1 (0.9-1.5) using modified VTE-BLEED score, 5.2 (3.3-7.8) and 1.5 (1.2-1.8) using modified HAS-BLED score, and 4.8 (1.3-12.4) and 1.7 (1.4-2.0) using modified outpatient bleeding index score. Modified versions of the ACCP, VTE-BLEED, and HAS-BLED scores help identify patients with unprovoked VTE who are at high risk of major bleeding and should be considered for discontinuation of anticoagulation after 3 to 6 months of initial treatment. The CHAP model may further improve estimation of bleeding risk by using continuous predictor variables, but external validation is required before its implementation in clinical practice.

Oral anticoagulants and outcomes in adults ≥80 years with atrial fibrillation: A global federated health network analysis.

The objective of this study was to determine associations between use of oral anticoagulation (OAC) and stroke and bleeding-related outcomes for older people ≥80 years with atrial fibrillation (AF), and to determine trends over time in prescribing of OAC for this population. A retrospective cohort study was conducted. People aged ≥80 years with AF receiving (1) no OAC; (2) warfarin; or (3) a non-vitamin-K antagonist oral anticoagulant (NOAC) between 2011 and 2019 were included. Propensity score matching was used to balance cohorts (no OAC, warfarin or a NOAC) on characteristics including age, sex, ethnicity, and co-morbidities. Cox proportional hazard models were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). The proportion of people aged ≥80 years receiving any OAC increased from 32.4% (n=27,647) in 2011 to 43.6% (n=110,412) in 2019. After propensity score matching, n=169,067 individuals were included in the cohorts receiving no OAC or a NOAC. Compared to no OAC, participants receiving a NOAC had a lower risk of incident dementia (hazHR 0.68, 95% CI 0.65-0.71), all-cause mortality (HR 0.49, 95% CI 0.48-0.50), first-time ischaemic stroke (HR 0.87, 95% CI 0.83-0.91), and a higher risk of major bleeding (HR 1.08, 95% CI 1.05-1.11). Compared to participants receiving warfarin, participants receiving a NOAC had a lower risk of dementia (HR 0.90, 95% CI: 0.86-0.93), all-cause mortality (HR 0.74, 95% CI: 0.72-0.76), ischaemic stroke (HR 0.86, 95% CI: 0.82-0.90) and major bleeding (HR 0.88, 95% CI: 0.85-0.90). Similar results were observed when only including people with additional bleeding risk factors. The proportion of people aged ≥80 years receiving OAC has increased since the introduction of NOACs, but remains low. Use of a NOAC was associated with improved outcomes compared to warfarin, and compared to no OAC, except for a small but statistically significant higher risk of major bleeding.