Higher Risk Of Major Bleeding Research Articles

Impact of Selective Serotonin-Reuptake Inhibitors in Hemorrhagic Risk in Anticoagulated Patients Taking Non-Vitamin K Antagonist Anticoagulants: A Systematic Review and Meta-analysis.

Studies show an increase in hemorrhagic risk related to selective serotonin-reuptake inhibitors (SSRIs) alone, but also in association with vitamin K antagonists (VKAs). Non-VKA anticoagulants (NOACs) can be a good substitute to VKAs, but the correlation between them and SSRIs is not well studied. Therefore, we conducted a systematic review to evaluate the risk of major bleeding associated with concomitant use of SSRIs and NOACs. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed databases were searched, in September 2022, for longitudinal studies evaluating SSRIs' impact on hemorrhagic risk in anticoagulated patients taking NOACs compared with a control group taking non-SSRI medication instead or no antidepressants at all. The outcome of interest was major bleeding. The quality of the included studies was assessed using the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled RRs with 95% confidence intervals (CIs), and heterogeneity was evaluated using the I2 statistic. Eight studies were included in the meta-analysis. From a population of 279,540 anticoagulated patients taking NOACs, the ones taking SSRIs concomitantly were associated with a higher risk of major bleeding (relative risk, 1.33; 95% CI, 1.06-1.66; I2 = 60%). However, the subgroup analysis of cohort studies did not achieve statistical significance (relative risk, 1.05; 95% CI, 0.94-1.66). The findings show that SSRIs are associated with a greater hemorrhagic risk in patients anticoagulated with NOACs; however, our confidence is reduced because of nonstatistically significant results from more robust studies, as cohort studies.

Incidence, source, and prognostic impact of major bleeding across the spectrum of aortic stenosis

Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity. To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity. Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement. Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (interquartile range: 1.4-2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64-9.65); P < .001). AS severity was associated with major bleedings (P=.041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 [95% confidence interval 1.56-8.29]; P=.003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation. In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.

Fatal, ischemic and bleeding risk of patients meeting the selection criteria of the TWILIGHT trial: Insights from a large PCI registry

The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3 month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population. Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. We stratified patients into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI. Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients. Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and myocardial infarction and a moderately elevated risk of bleeding.

Trajectories of Oral Anticoagulation Adherence and Associated Clinical Outcomes During Long-Term Anticoagulation Among Medicare Beneficiaries With Venous Thromboembolism.

Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice. We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks. Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models. Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk. This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk.

Valor pronóstico de la fibrosis hepática valorada por el índice FIB4 en pacientes ingresados por síndrome coronario agudo

Introduction and objectivesLiver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). MethodsRetrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). ResultsWe included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). ConclusionsThe assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.Full English text available from:www.revespcardiol.org/en

Impact of amiodarone on plasma concentration of direct oral anticoagulant in patients with atrial fibrillation

Amiodarone increases exposure of direct oral anticoagulants (DOACs). We aimed to analyze the effects of concurrent amiodarone use on DOAC concentrations and clinical outcomes. Patients who were ≥20 years of age, had atrial fibrillation, and took DOAC were enrolled to provide trough and peak samples for DOAC concentration measurements using ultra-high-performance liquid chromatography-tandem mass spectrometry. The results were compared with concentrations reported in clinical trials to define above, within, or under the expected range. The outcomes of interest were major bleeding and any gastrointestinal bleeding. Multivariate logistic regression and Cox proportional hazards model were used to determine the impact of amiodarone on above-range concentration and clinical outcomes, respectively. A total of 722 participants (420 men, 58.2%) were enrolled to provide 691 trough samples and 689 peak samples. Among them, 21.3% concurrently used amiodarone. The proportion of patients with above-range trough and peak concentrations was 16.4% and 30.2%, respectively, for amiodarone users, in contrast to 9.4% and 19.8% for amiodarone non-users. The use of amiodarone was associated with above-range trough and peak concentrations (odds ratio [OR]=2.00 [1.16, 3.47] and 1.82 [1.19, 2.79], respectively). However, amiodarone was not a significant predictor of major bleeding or any gastrointestinal bleeding. Concurrent amiodarone use led to increased DOAC concentration but was not associated with a higher risk of major bleeding or any gastrointestinal bleeding. Therapeutic monitoring of DOAC users concurrently taking amiodarone may be recommended for patients with an additional risk of increased DOAC exposure.

Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR

BackgroundIn the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban was noninferior to vitamin K antagonists (VKA) for a composite outcome of ischemic and bleeding complications but increased major bleeding in patients with atrial fibrillation after successful transcatheter aortic valve replacement. Women are at higher risk of bleeding and stroke than men after transcatheter aortic valve replacement. It is unclear whether the effect of edoxaban on these complications varies in relation to sex. ObjectivesThis study was to assess the effect of edoxaban vs VKA according to sex in the ENVISAGE-TAVI AF trial. MethodsThe primary outcomes were net adverse cardiovascular events (NACE) and major bleeding, assessed considering the effective time on study medication (safety analysis). ResultsOut of 1,377 patients, 658 (47.8%) were women. Risks for ischemic and major bleeding outcomes were similar between women and men. Edoxaban compared to VKA was associated with a similar risk of NACE in women (HR: 1.16; 95% CI: 0.81-1.65) and men (HR: 1.08; 95% CI: 0.76-1.53; P for interaction = 0.820) and a higher risk of major bleeding in both sexes (P for interaction = 0.170). The risk increase of major bleeding was attenuated in women (HR: 1.11; 95% CI: 0.69-1.79) as compared to men (HR: 1.75; 95% CI: 1.07-2.85). There were no treatment-related differences for ischemic complications in both sexes. ConclusionsEdoxaban compared to VKA was associated with a similar risk of NACE and higher risk of major bleeding in both sexes. The increase in bleeding complications with edoxaban was attenuated in women.

Effects of Simvastatin on Pharmacokinetics and Anticoagulant Effects of Dabigatran in Healthy Subjects.

Higher risk of major hemorrhage associated with concomitant use of dabigatran and simvastatin compared to other statins was previously reported with a suggestion of P-glycoprotein-mediated interaction. The aim of this study was to evaluate the effects of simvastatin on pharmacokinetics and anticoagulant effects of dabigatran, a direct oral anticoagulant. A total of 12 healthy subjects were enrolled in an open-label, two-period, single sequence study. Subjects were given 150 mg of dabigatran etexilate followed by 40 mg of once-daily simvastatin for seven days. Dabigatran etexilate was administered with simvastatin on the seventh day of simvastatin administration. Blood samples for pharmacokinetic and pharmacodynamic analyses were obtained until 24 h post-dose of dabigatran etexilate with or without co-administration of simvastatin. Pharmacokinetic parameters were derived from noncompartmental analysis for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide. When simvastatin was co-administered, geometric mean ratios of area under time-concentration curves for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide were 1.47, 1.21, and 1.57, respectively, compared to when dabigatran etexilate was administered alone. Thrombin generation assay and coagulation assay showed similar profiles between before and after co-administration of simvastatin. This study provides evidence that simvastatin treatment plays a minor role in modulating pharmacokinetics and anticoagulant effects of dabigatran etexilate.

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

De-escalation in intensity or duration of dual antiplatelet therapy in patients with coronary artery disease: More than alternative treatment options

Antithrombotic therapy represents the mainstay of pharmacological treatments in patients with acute or chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI) [ [1] De Servi S. Landi A. Savonitto S. et al. Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice. J Cardiovasc Med. 2023; 24 Crossref Scopus (1) Google Scholar ]. Since the CURE study [ [2] Mehta S.R. Yusuf S. Peters R.J.G. et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001; 358: 527-533 Abstract Full Text Full Text PDF PubMed Scopus (3042) Google Scholar ], dual antiplatelet therapy (DAPT) consisting of aspirin and an oral P2Y12 inhibitor has represented the standard of care for acute coronary syndrome (ACS) or PCI patients due to the greater ischemic protection compared with aspirin alone. Current guidelines recommend 6 or 12 months as default DAPT durations in patients with CCS or ACS undergoing PCI, respectively [ [3] Valgimigli M. Bueno H. Byrne R.A. et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018; 39: 213-260 Crossref PubMed Scopus (1840) Google Scholar , [4] Collet J.-.P. Thiele H. Barbato E. et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021; 42: 1289-1367 Crossref PubMed Scopus (1705) Google Scholar ]. Yet, there is mounting evidence suggesting that prolonging DAPT is unavoidably associated with higher risks of major bleeding which carry similar or even worse impact on mortality than a recurrent myocardial infarction (MI) [ [5] Valgimigli M. Landi A. Ischemic and bleeding risk in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention: is it time to REACT?. Eur Heart J Acute Cardiovasc Care. 2021; 10: 1125-1128 Crossref PubMed Google Scholar ].

Abstract 3: Cerebral Small Vessel Disease Burden For Bleeding Risk During Antithrombotic Therapy -BAT2-

Background: Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs. Purpose: To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden. Methods: Patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were prospectively enrolled from 52 hospitals across Japan between 2016 and 2019. Multimodal brain MRI was acquired at baseline for all patients under prespecified conditions. All MRI examinations were interpreted by a central diagnostic radiology committee for cerebral microbleeds, lacunes, white matter hyperintensities, and enlarged basal ganglia perivascular spaces, for calculation of a total SVD score (range 0-4). The primary outcome was major bleeding during 2-year follow-up. Secondary outcomes included bleeding in each site and ischemic events. Event risks according to SVD score were estimated with multivariable Cox proportional hazards models. Results: Of the analyzed 5250 patients (1736 women; median age, 73 years; 9933 patient-years follow-up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median of the total SVD score was 2 (IQR 1-3). As SVD score increased, advanced age, hypertension, anemia, and chronic kidney disease were more prevalent (P&lt;0.001 for each). A unit increase of SVD score was associated with a higher risk of major bleeding (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.29-1.85) and intracranial hemorrhage (adjusted HR 1.61, 95% CI 1.28-2.03). With SVD score 4 compared to score 0, extracranial major bleeding (adjusted HR 3.37, 95% CI 1.12-10.15) and gastrointestinal bleeding (adjusted HR 2.54, 95% CI 1.02-6.35) were also significantly increased. A higher SVD score was associated with a mild but significant elevation of ischemic event risk (adjusted HR per unit increase 1.17, 95% CI 1.06-1.29). Conclusions: The total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting a broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy.

Antiplatelet Agents and Oral Anticoagulant Use in Patients with Atrial Fibrillation and Carotid Artery Disease After First-Time Ischaemic Stroke

IntroductionPeople with atrial fibrillation (AF) frequently have competing mechanisms for ischaemic stroke, including extracranial carotid atherosclerosis. The objective of this study was to determine associations between use of oral anticoagulants (OACs) plus antiplatelet agents (APA) after ischaemic stroke and outcomes for patients with AF and carotid artery disease.Patients and MethodsA retrospective cohort study was conducted. Participants receiving OACs with or without APA were propensity score–matched for age, sex, ethnicity, co-morbidities and presence of cardiac and vascular implants and grafts. Outcomes were 1-year mortality, recurrent stroke and major bleeding.ResultsOf 5708 patients, 24.1% (n=1628) received non-vitamin K antagonist OACs (NOACs) with no APA, 26.0% (n=1401) received NOACs plus APA, 20.7% (n=1243) received warfarin without APA and 29.2% (n=1436) received warfarin plus APA. There was no significant difference in risk of recurrent stroke between the groups. Compared to receiving NOACs without APA, receiving warfarin plus APA was associated with a higher risk of mortality (hazard ratio (HR) 1.51 (95% confidence interval (CI) 1.20, 1.89)) and major bleeding (HR 1.66 (95% CI 1.40, 1.96)). Receiving NOACs plus APA was also associated with a higher risk of major bleeding compared to NOACs without APA (HR 1.27 (95% CI 1.07, 1.51), respectively).ConclusionsThe results suggest for patients with AF and carotid artery disease after ischaemic stroke, receiving NOACs without APA is associated with a lower risk of major bleeding with no negative impact on recurrent stroke or mortality. Evidence from randomised trials is needed to confirm this finding.

Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome

Introduction and objectivesLiver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). MethodsRetrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). ResultsWe included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). ConclusionsThe assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.

Reduced dose direct oral anticoagulants compared with warfarin with high time in therapeutic range in nonvalvular atrial fibrillation

Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78–0.93), intracranial bleeding HR 0.64 (0.51–0.80), hemorrhagic stroke HR 0.68 (0.50–0.92), gastrointestinal bleeding HR 0.81 (0.69–0.96) and all-cause stroke HR 0.87 (0.76–0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63–0.78) and HR 0.80 (0.69–0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59–0.96), with higher major bleeding risk, HR 1.31 (1.15–1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03–1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting.

Thromboprophylaxis in Hospitalized Non-Critically Ill Patients With Mild-to-Moderate COVID-19 Infection: A Systematic Review and Meta-Analysis.

The prevalence of venous thromboembolism is high in patients with COVID-19, despite prophylactic anticoagulation. The evidence that supports the preferred thromboprophylaxis regimen in non-critically ill patients with mild to moderate COVID-19 is still limited. Therefore, this systematic review and meta-analysis aimed to compare the clinical outcomes of hospitalized patients with mild to moderate COVID-19 who received standard thromboprophylaxis anticoagulation with intermediate to high prophylaxis regimens. We systematically searched MEDLINE and Embase databases for published studies until August 17th, 2022. We included studies on patients with mild to moderate COVID-19 who received thromboprophylaxis during their hospital stay. Patients who received standard prophylaxis dose "control group" were compared to patients who received intermediate to high prophylaxis "intervention group". Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes. A comprehensive analysis was conducted, encompassing seven studies involving a total of 1931 patients. The risk of all-cause thrombosis was not statistically different between the two groups (risk ratio [RR] 1.48, 95% confidence interval [CI] [0.11, 20.21]). The risk of minor bleeding was reported to be lower in patients who received intermediate to high prophylaxis (RR 0.64, 95% CI 0.21, 1.97), while had a higher risk of major bleeding compared with the standard prophylaxis (RR 1.40, 95% CI 0.43, 4.61); however, did not reach the statistical significance. The overall risk for all hospital mortality favored the utilization of intermediate to high doses over the standard thromboprophylaxis dosing (RR 0.47, 95%CI 0.29, 0.75). In medically ill patients with COVID-19, there is no difference between standard and intermediate to high prophylaxis dosing regarding thrombosis and bleeding. However, it appears that intermediate to high prophylaxis regimens are linked to additional survival benefits.

Sex-Related Bleeding Risk in Acute Coronary Syndrome Patients Receiving Dual Antiplatelet Therapy with Aspirin and a P2Y12 Inhibitor

Objective: The aim of this work was to study sex differences in major bleeding risk in relation to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Methods and Results: The Rijnmond Collective Cardiology Research registry was designed to evaluate the application and outcomes of DAPT after ACS/PCI in the Rijnmond region in the Netherlands. Overall, 1,172 women (median age 67.5 years) and 3,087 men (median age 62.2 years) with ACS/PCI were enrolled between August 2011 and June 2013. Based on a tailored regional DAPT guideline aiming at bleeding risk minimization, 52.6% women and 66.9% men received prasugrel as first-choice P2Y12 inhibitor, in addition to aspirin. Women more frequently had contraindications for the use of prasugrel (and therefore received clopidogrel) than men (47.9 vs. 26.9%, p < 0.001). Femoral access was more common in women than in men (47.6 vs. 38.1%, p < 0.001). Women had higher incidence of major bleeding at 1 year than men (2.6 vs. 1.6%, p = 0.018). After adjustment for established bleeding risk factors, female sex was associated with over two-fold higher risk of major bleeding (adjusted hazard ratio 2.33; 95% confidence interval 1.26–4.32). This difference was apparent at discharge and appeared to be caused by access site bleedings (0.9 vs. 0.1%, p < 0.001). No sex differences were found in non-access site-related major bleeding up to 1 year. Conclusion: Women with ACS/PCI receiving DAPT had higher major bleeding risk caused by an excess in access site bleeds, mainly in relation to the femoral approach.

759 LEFT MAIN PERCUTANEOUS OR SURGICAL REVASCULARIZATION AND SUBSEQUENT RISK OF ACUTE KIDNEY INJURY: INSIGHTS FROM THE LUCKY REGISTRY

Abstract Background Recent evidence has rendered percutaneous coronary intervention (PCI) a valuable alternative to coronary artery bypass grafting (CABG) in patients with left main coronary artery disease (LMCAD). Nevertheless, the optimal management and patients selection is still subject to discussion Methods We retrospectively included 431 patients treated with PCI and 324 patients treated with CABG with the primary objective of comparing procedural failure according to revascularization strategy. Secondary endpoints were post procedural and clinically relevant myocardial infarction, in-hospital stroke, major bleeding defined according to the Bleeding Academic Research Consortium (BARC) criteria, death, and 1-year major adverse cardiac events (MACE). Results There was no observed difference in the rates of procedure failure in patients who received PCI compared to patients who received CABG (4.6% vs 3.7%, respectively) odds ratio [OR] 1.26; (95% confidence intervals [CI] 0.58-2.9, p= 0.52.) There was no significant difference in the defined ischemic outcome for PCI vs CABG (0.9% vs 2.4%, respectively) OR 0.37; (95% CI 0.08-1.4), P = 0.09. There was a mild increase in periprocedural myocardial infarction (MI) after PCI (4.2% vs 1.5%) compared to CABG; (OR = 2.8; 95% CI 0.99-9.8, P = 0.034). On the contrary there was a higher risk of major bleeding and transfusions in the patients who had been treated with CABG who has a clinical profile suited for PCI. Conclusions PCI did not significantly increase the risk for procedural failure or ischemic events compared to CABG in patients with LM CAD. The higher risk for post-procedural MI after PCI was offset by a higher risk for major bleeding events and transfusion requirements in those undergoing CABG, especially for those who were clinically suited for PCI.

760 IMPACT OF COMORBIDITIES AND PATIENTS PREFERENCE ON THE CHOICE BETWEEN PERCUTANEOUS OR SURGICAL REVASCULARIZATION FOR LEFT MAIN CORONARY ARTERY DISEASE

Abstract Background Recent evidence has rendered percutaneous coronary intervention (PCI) a valuable alternative to coronary artery bypass grafting (CABG) in patients with left main coronary artery disease (LMCAD). Nevertheless, the optimal management and patients selection is still subject to discussion Methods We retrospectively included 431 patients treated with PCI and 324 patients treated with CABG with the primary objective of comparing procedural failure according to revascularization strategy. Secondary endpoints were post procedural and clinically relevant myocardial infarction, in-hospital stroke, major bleeding defined according to the Bleeding Academic Research Consortium (BARC) criteria, death, and 1-year major adverse cardiac events (MACE). Results There was no observed difference in the rates of procedure failure in patients who received PCI compared to patients who received CABG (4.6% vs 3.7%, respectively) odds ratio [OR] 1.26; (95% confidence intervals [CI] 0.58-2.9, p= 0.52.) There was no significant difference in the defined ischemic outcome for PCI vs CABG (0.9% vs 2.4%, respectively) OR 0.37; (95% CI 0.08-1.4), P = 0.09. There was a mild increase in periprocedural myocardial infarction (MI) after PCI (4.2% vs 1.5%) compared to CABG; (OR = 2.8; 95% CI 0.99-9.8, P = 0.034). On the contrary there was a higher risk of major bleeding and transfusions in the patients who had been treated with CABG who has a clinical profile suited for PCI. Conclusions PCI did not significantly increase the risk for procedural failure or ischemic events compared to CABG in patients with LM CAD. The higher risk for post-procedural MI after PCI was offset by a higher risk for major bleeding events and transfusion requirements in those undergoing CABG, especially for those who were clinically suited for PCI.

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 &lt; 1.1. The risk of IS/SE was lower for patients having an INR ≥ 1.5 compared to those with an INR &lt; 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 &lt; 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.