Incidence Of Major Bleeding Events Research Articles

Shortened Duration of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Contemporary Clinical Review

Percutaneous coronary intervention with stent implantation is an integral aspect of minimally interventional cardiac procedures. The technology and techniques behind stent design and implantation have evolved rapidly over several decades. However, continued discourse remains around optimal peri- and post-interventional management with dual antiplatelet therapy to minimise both major cardiovascular or cerebrovascular events and iatrogenic bleeding risk. Standard guidelines around dual antiplatelet therapy historically recommended long-term dual antiplatelet therapy for 12 months (with consideration for >12 months in certain patients); however, emerging data and generational improvements in the safety of drug-eluting stents have ushered in a new era of short-term therapy to reduce the incidence of major bleeding events. This case review will provide an overview of the current state of guidelines around duration of dual antiplatelet therapy and examine recent updates and continued gaps in existing research.

Benefit of Anticoagulation Early After Surgical Aortic Valve Replacement Using Bioprosthetic Valves.

To compare all-cause mortality and thromboembolic events in patients undergoing surgical aortic valve replacement (sAVR) receiving anticoagulation with warfarin versus patients with no systemic anticoagulation. Using data from the OptumLabs Data Warehouse, we investigated adult patients having bioprosthetic sAVR with or without coronary artery bypass from January 1, 2007, through December 31, 2019. Patients were classified into groups of nonwarfarin or warfarin (≥30 days of continuous prescription coverage after sAVR). One-to-one propensity score (PS) matching was used to adjust for group differences. Of 10,589 patients having sAVR, 7659 (72.3%) were in the nonwarfarin group and 2930 (27.7%) were in the warfarin group. After PS matching, 2930 pairs of patients were analyzed. Median follow-up was 4.1 months (interquartile range [IQR], 2.6-7.4 months) for the warfarin group and 21.3 months (IQR, 7.8-24.0 months) for the nonwarfarin group. Overall mortality was lower for the warfarin group than for the nonwarfarin group (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47 to 1.00; P=.047), and there was a trend toward decreased cumulative incidence of thromboembolic events (subdistribution HR [SHR], 0.62; 95% CI, 0.35 to 1.07; P=.09). Cumulative incidence of major bleeding events was higher for the warfarin group vs the nonwarfarin group (SHR, 1.94; 95% CI, 1.28 to 2.94; P=.002). Results were similar in a subgroup analysis of patients undergoing isolated sAVR. During the prescription coverage period, warfarin use after bioprosthetic sAVR was associated with lower all-cause mortality and decreased risk of thromboembolism compared with not receiving warfarin. However, warfarin use was associated with an increased risk of major bleeding events.

Spontaneous Laryngeal Hematoma: A Rare Presentation of Supratherapeutic INR

Introduction: Warfarin is one of the most routinely used drugs for anticoagulation. However, it poses a significant bleeding risk. Incidence of major bleeding events ranges from 0.4-7.2% per year, and that of minor bleeding events can be as high as 15.4% per year. Here we present a rare case of laryngeal hematoma due to supratherapeutic INR. Case description: A 48-year-old male with past medical history of hypertension, Insulin dependent diabetes mellitus, and multiple episodes of deep venous thromboses on chronic anticoagulation with warfarin presented to the emergency department complaining of left sided neck pain and hoarseness of voice that started and progressively worsened since the past 24 hours. He denies any fever, chills, cough, shortness of breath, or dental pain. He was found to be hemodynamically stable with no oxygen requirement. He spoke with a hoarse voice, but no stridor was noted. Tenderness of the left anterior triangle of the neck below the jawline and mild trismus was noted. Laboratory work-up showed stable hemoglobin of 12.2 and a supratherapeutic INR of 9.9. CT of soft tissue neck showed retropharyngeal fluid collection extending from skull base to C7 with mild to moderate supraglottic airway narrowing. Flexible nasopharyngeal endoscopy showed significant collection of secretions with omega shaped epiglottis and retropharyngeal swelling, raising concerns for a hematoma. INR reversal with 2 units of fresh frozen plasma was initiated and patient was transferred to medical intensive care unit. He underwent daily endoscopies for three days; on day 3 significant improvement of the hematoma size was noted. Daily oral Vitamin K for 3 days ensured INR reversal from 9.9 to 1.7. After transferring to floors, the patient was gradually re-started on his anticoagulation and discharged home safely. Discussion: This case exemplified one of the rare but life-threatening complications of supratherapeutic INR. Bleeding into the larynx is a very rare life-threatening complication of chronic anticoagulation with warfarin. Similar case was reported by Cody A. Koch et al in 2010. In 2017 another case was reported which resulted in death from asphyxia before patient was taken to the hospital. A patient with similar presentation and demographics with the index case was reported also in 2019. As per literature, this case will be one of the very few reported cases of Spontaneous laryngeal hematoma due to supratherapeutic INR. Several factors could potentially affect the INR level of patients on chronic warfarin therapy and can cause acute elevation of INR which can lead to several complications including epiglottal hematoma as seen in this case. The index patient has significant history of chronic diarrhea along with OTC Tylenol ingestion for chronic patient both of which can cause INR increase. Thus, high index of suspicion is important especially for patients with comorbidities due to the fragile interaction of warfarin with several common medications and clinical conditions. Epiglottal hematoma can expand and potentially compromise the airway if immediate reversal of supratherapeutic INR is not commenced. Regardless of presentation, every patient who exhibits warfarin-associated upper airway hemorrhage should receive treatment that includes stopping anticoagulation, correcting the coagulopathy quickly, closely monitoring the patient's airway in an intensive setting, and having a low threshold for tracheostomy. Given the predicted difficulty with direct and fiberoptic laryngoscopy, the delayed time course for hematoma clearance, and the potential trauma resulting in further bleeding in an anticoagulated patient, securing the airway via intubation is frequently not desirable. Such cases of non-traumatic hemorrhage may be managed medically or surgically. Spontaneous hemorrhage is usually managed conservatively. Regarding the ideal course of treatment, there is, however, no agreement. Conclusion: There is need for a high index of suspicion for atypical presentations of supratherapeutic INR (including bleeding into the airway) in patients on prolonged anticoagulation with warfarin. The need for immediate reversal and routine INR monitoring in these patients is also emphasized in this clinical vignette.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention

BackgroundThe optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. MethodsPatients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. ResultsAmong 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). ConclusionsThe APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Low-molecular-weight heparin therapy reduces 28-day mortality in patients with sepsis-3 by improving inflammation and coagulopathy.

Sepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required. We performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria. After 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, p = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, p = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29-0.81; p = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20-35 or SOFA score 8-12). Our study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.

Association of preoperative clinical frailty and clinical outcomes in elderly patients with stable coronary artery disease after percutaneous coronary intervention.

There are few reports on the long-term clinical outcome after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) complicated with frailty. This novel study investigated the association between pre-PCI frailty and long-term clinical outcomes in elderly patients aged 65years or older with stable CAD who underwent elective PCI. We assessed 239 consecutive patients aged 65years or older with stable CAD who underwent successful elective PCI at Kagoshima City Hospital between January 1st, 2017 and December 31st, 2020. Frailty was retrospectively assessed using the Canadian Study and Aging Clinical Frailty Scale (CFS). Based on the pre-PCI CFS, patients were divided into two groups: the non-frail (CFS < 5) and the frail (CFS ≥ 5) group. We investigated the association between pre-PCI CFS and major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and heart failure requiring hospitalization. Additionally, we assessed the association between pre-PCI CFS and major bleeding events defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The mean age was 74.8 ± 7.0years, and 73.6% were men. According to the pre-PCI frailty assessment, 38 (15.9%) and 201 (84.1%) were classified as frail and non-frail groups, respectively. During a median follow-up of 962 (607-1284) days, 46 patients developed MACEs and 10 patients developed major bleeding events. Kaplan-Meier curves showed a significantly higher incidence of MACE in the frail group compared to those in the non-frail group (Log-rank p < 0.001). Even in multivariate analysis, pre-PCI frailty (CFS ≥ 5) was independently associated with MACE (HR 4.27, 95% CI 1.86-9.80, p-value: < 0.001). Additionally, the cumulative incidence of major bleeding events was significantly higher in the frail group than in the non-frail group (Log-rank p = 0.001). Pre-PCI frailty was an independent risk factor for MACE and bleeding events in elderly patients with stable CAD who underwent elective PCI.

Validation of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in patients undergoing peripheral endovascular interventions.

It remains unclear whether the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria could apply to peripheral artery disease (PAD) patients undergoing endovascular therapy (EVT). We sought to evaluate the application of the ARC-HBR criteria to PAD patients undergoing EVT with contemporary drug-coated devices (DCD) for femoropopliteal artery lesions. Between May 2012 and December 2019, 542 consecutive patients undergoing EVT with DCD for femoropopliteal artery lesions were retrospectively analysed. The primary study endpoint was major bleeding events, defined as Bleeding Academic Research Consortium type 3 or 5. Of 542 patients, 435 (80.3%) were stratified into the HBR group. The cumulative 5-year incidence of major bleeding events was significantly higher in the HBR group than in the non-HBR group (31.9% vs 2.3%; p<0.001). The 5-year major bleeding event rate gradually increased with the number of ARC-HBR criteria (≥2 major criteria: 48.6%, 1 major: 33.1%, ≥2 minor: 12.9%, and non-HBR: 2.3%; p<0.001). Major bleeding events were associated with a 5.4-fold increased risk of mortality (adjusted hazard ratio: 5.42, 95% confidence interval: 2.91-10.1; p<0.001). Severe chronic kidney disease, heart failure, and severe anaemia were predictors of major bleeding events. 80.3% of PAD patients undergoing EVT for femoropopliteal artery lesions with contemporary drug-coated devices met the ARC-HBR criteria. Given that major bleeding events remarkably increased the risk of mortality after EVT, the ARC-HBR criteria might be helpful for the risk stratification of PAD patients who undergo EVT with contemporary DCD.

Effect of pretreatment with a P2Y12 inhibitor in patients with non-ST-elevation acute coronary syndrome: a systematic review and network meta-analysis.

This study aimed to systematically evaluate the effects of different types and doses of pretreatment with P2Y12 inhibitors in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). Electronic databases were searched for studies comparing pretreatment with different types and doses of P2Y12 inhibitors or comparison between P2Y12 inhibitor pretreatment and nonpretreatment. Electronic databases included the Cochrane Library, PubMed, EMBASE, and Web of Science. Literature was obtained from the establishment of each database until June 2022. The patients included in the study had pretreatment with P2Y12 inhibitors with long-term oral or loading doses, or conventional aspirin treatment (non-pretreatment). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) during follow-up within 30 days after PCI, which included determining the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The safety endpoint was a major bleeding event. A total of 119,014 patients from 21 studies were enrolled, including 13 RCTs and eight observational studies. A total of six types of interventions were included-nonpretreatment (placebo), clopidogrel pretreatment, ticagrelor pretreatment, prasugrel pretreatment, double loading pretreatment (double loading dose of clopidogrel, ticagrelor, prasugrel) and P2Y12 inhibitors pretreatment (the included studies did not distinguish the types of P2Y12 inhibitors, including clopidogrel, ticagrelor, and prasugrel). The network meta-analysis results showed that compared to patients without pretreatment, patients receiving clopidogrel pretreatment (RR = 0.78, 95% CI:0.66, 0.91, P < 0.05) and double-loading pretreatment (RR = 0.62, 95% CI:0.41, 0.95, P < 0.05) had a lower incidence of MACCEs. There was no statistically significant difference in the incidence of major bleeding events among the six pretreatments (P > 0.05). In patients with NSTE-ACS, pretreatment with P2Y12 inhibitors before percutaneous intervention reduced the incidence of recurrent ischemic events without increasing the risk of major bleeding after PCI compared with nonpretreatment. Clopidogrel or double loading dose P2Y12 inhibitors can be considered for the selection of pretreatment drugs.

512 ACADEMIC RESEARCH CONSORTIUM HIGH BLEEDING RISK CRITERIA ASSOCIATED WITH ONE-YEAR NACES IN A MULTICENTER COHORT OF OLDEST OLD STEMI PATIENTS

Abstract Introduction The balance between thrombotic and bleeding events after myocardial revascularization is of paramount importance. Patients with higher bleeding risk are at high risk for complications. Age and frailty are also major risk factors for complications. We sought to evaluate the incidence of major bleeding events (BE) and their impact on prognosis in a real life oldest old (i.e. &amp;gt;85 years) ST elevation myocardial infarction (STEMI) patients population. Methods We evaluated all consecutive oldest old STEMI patients hospitalized in two hub-centers between January 2010 and June 2021. Patients were stratified according to Academic Research Consortium for High Bleeding Risk (ARC-HBR) in high bleeding risk (HR) and non-HR (nHR) patients. BE were defined according to the Bleeding Academic Research Consortium (BARC) criteria, BARC 3 or 5. Patients were also divided in groups according to anti-thrombotic therapy (AT) regimens at discharge: single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT) or triple therapy (DAPT plus oral anticoagulation) (TT). Net adverse clinical event (NACE) was defined as a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding. Follow-up data were determined from local clinical records during a twelve-months period. Results 340 oldest old (mean age 88.6 ± 2.9 years, 52.6% female) STEMI patients were eligible for the analysis. 161 patients (47.4%) were categorized as nHR and 179 patients (52.6%) as HR. AT regimens at discharge were: 28 patients with SAPT (8.2%), 276 with DAPT (81.2%) and 36 with TT (10.6%). The overall incidence of BE was 4.6% within 12 months, without difference between nHR and HR patients (3.0% vs 5.9%, p=0.16). No BE were found in the SAPT group while the incidence of BE in the HR group was not statistically different between the DAPT and TT regimens (11.2% vs 9.5%; p=0.8). The incidence of NACE was statistically higher in HR than nHR patients (40.9% vs 25.5%, p&amp;lt;0.01) at 1-year. In addition, time-to-NACE was statistically inferior in HR group than nHR group (256.2 days vs 294.2 days, p&amp;lt;0.01) (Figure). Conclusions Our oldest old STEMI population was characterized by a large proportion of HR patients according to ARC-HBR criteria. This population experienced a higher rate of NACE in a shorter time when compared to nHR patients in the same age group.

The impact of ABCB1 and CES1 polymorphisms on the safety of dabigatran in patients with non-valvular atrial fibrillation

BackgroundThis study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF).MethodsWe conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up.ResultsEighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events.ConclusionOur results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.

Rivaroxaban Treatment for Patients With Unprovoked or Provoked Venous Thromboembolism - Subanalysis of the J'xactly Study.

Background: The efficacy and safety of direct oral anticoagulants (DOACs) in patients with unprovoked venous thromboembolism (VTE) remain unclear.Methods and Results: In this subanalysis of the J’xactly study, a multicenter prospective observational study, we evaluated the safety and effectiveness of rivaroxaban in patients with acute VTE according to unprovoked (n=388) or provoked (n=557) VTE status. Median follow-up was 21.2 months. Compared with patients in the provoked group, patients in the unprovoked group were younger, less likely to be female, and had higher body weight. The incidence of symptomatic VTE recurrence was significantly higher in the unprovoked than provoked VTE group (3.54% vs. 1.77% per patient-year; P=0.032). There was no significant difference in the incidence of major bleeding events between rivaroxaban-treated patients with unprovoked and provoked VTE (2.31% vs. 3.75% per patient-year; P=0.289). Although the proportion of patients with a body mass index (BMI) ≥25 kg/m2 who were non-users of antiplatelet agents was higher in the unprovoked VTE group, there was no interaction effect (BMI: 4.58% vs. 1.55% per patient-year [P=0.040; P for interaction=0.361]; concomitant antiplatelet agent non-users: 3.65% vs. 1.72% per patient-year [P=0.028; P for interaction=0.627]).Conclusions: This subanalysis suggests the safety and effectiveness of rivaroxaban in patients with unprovoked VTE. In such patients, DOAC discontinuation should be considered carefully, particularly in those not using antiplatelet agents and those with a high BMI.

Incidence and risk factors for major bleeding events in atrial fibrillation patients on direct oral anticoagulant therapy: data from the National Patient-Centered Clinical Research Network

Abstract Background Direct oral anticoagulation (DOACs) prevent stroke in patients with atrial fibrillation (AF) and have a superior safety profile compared with vitamin K antagonists (VKA). Yet, better definition of incidence and risk factors for major bleeding associated with DOACs in clinical practice may be important given emerging stroke prevention technologies, both pharmacologic and nonpharmacologic. Purpose To describe the incidence of and risk factors for major bleeding in individuals with AF on DOAC therapy. Methods We reviewed electronic health record data for two patient cohorts with AF prescribed DOACs: (1) Duke University Health System (DUHS) (2010–2018) and (2) Sites within the Patient-Centered Clinical Research Network (PCORnet) (2015–2019) which had ≥6 years assimilated data from both inpatient and outpatient encounters (7 sites). In each cohort, we assessed the 5-year incidence of major bleeding events defined as hospitalization for intracranial hemorrhage, or hospitalization for gastro-intestinal bleeding or procedure to control bleeding accompanied by transfusion within ±7 days or death within 30 days. Multivariable Fine-Gray proportional hazards modeling in each cohort was performed to evaluate independent risk factors for major bleeding on DOAC therapy. Results The cohorts included 10,625 patients (DUHS) and 58,321 patients (PCORnet) with AF. Major bleeding events occurred within 5 years of diagnosis in 639 (7.9%) of DUHS patients and 2568 (6.6%) of PCORnet patients (Table 1). The DUHS model predicted time to first major bleeding event with a C-index of 0.756 (95% CI 0.737, 0.775) and the PCORNet model had a c-index of 0.745 (0.736, 0.755) (Table 2). Independent factors associated with major bleeding consistent across both models (p&amp;lt;0.001 in PCORnet for all unless noted) were higher CHA2DS2-VASc scores, lower eGFR, anemia (HR per 1-point increase in hemoglobin up to 12 g/dL 0.79 [0.76, 0.82]), prior major bleeding (HR 2.70 [2.22, 3.30]), cancer (HR 1.23 [1.12, 1.36]), recent cardiac surgery (HR 0.70 [0.51, 0.97]; p=0.030), alcohol use (HR 1.56 [1.29, 1.88]), aspirin use (HR 1.44 [1.32, 1.57]), and selective serotonin reuptake inhibitor use (HR 1.30 [1.19, 1.42]). Conclusions Across a large and geographically diverse contemporary population, risk of bleeding on DOAC for stroke prevention in AF remains a frequent and important clinical problem. There is an unmet need for stroke prevention therapies with improved safety profiles. We identified risk factors for major bleeding events on DOAC therapy, some of which are not represented in traditional risk scores, which may inform shared decision making for stroke prevention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Pharmaceuticals

Comparison of Efficacy and Safety of Anticoagulant Monotherapy and Combined Therapy of Anticoagulant and Antiplatelets in Patients With Stable Coronary Artery Disease and Atrial Fibrillation: A Meta-Analysis

It is still uncertain whether patients with atrial fibrillation (AF) andstable coronary artery disease (CAD) who require long-term oral anticoagulation (OAC) should also receive antiplatelet treatment (APT). This meta-analysis aims to compare the efficacy and safety of OAC alone with OAC plus APT in individuals with AF and stable CAD. The current meta-analysis was conducted as per the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE).We performed electronic searches using PubMed, EMBASE, and Cochrane Library. The efficacy outcomes assessed in this meta-analysis included cardiovascular death, myocardial infarction, stroke (ischemic and hemorrhagic), and all-cause mortality. The safety outcome included major bleeding events. A total of five studies were included in the current meta-analysis enrolling 9199 patients with stable CAD and AF. Out of these five studies, three were observational and two were randomized controlled trials (RCTs). Our study showed no significant difference between two groups in the incidence of cardiovascular mortality (Hazard ratio {HR}: 0.86, 95% confidence interval {CI}: 0.59-1.25, I-square: 44%), myocardial infarction (HR: 1.21, 95% CI: 0.73-2.01, I-square: 0%), all-cause mortality (HR: 0.95, 95% CI: 0.76-1.19, I-square: 68%) and stroke (HR: 0.83, 95% CI: 0.61-1.12, I-square: 45%). However, lower incidence of major bleeding events in patients who received OAC alone as compared to patients who received a combination of OAC and anti-platelet (HR: 1.37, 95% CI: 1.18-1.580, I-square: 78%) were found. The current meta-analysis showed that OAC monotherapy is associated with a lower incidence of major bleeding events in patients with stable CAD and AF. It is also not associated with an increased risk of all-cause mortality, cardiovascular death, stroke, and myocardial infarction.

Short-term efficacy and safety of edoxaban for venous thromboembolism after total hip or knee arthroplasty: a systematic review and meta-analysis.

Previous preliminary clinical trials have confirmed that edoxaban can be efficacious for venous thromboembolism (VTE). This meta-analysis was considered to evaluate edoxaban's short-term efficacy and safety for venous thromboembolism after arthroplasty. A comprehensive search was performed in these databases: PubMed, MEDLINE, Web of Science, and EMBASE on March 2022. All eligible trials should be randomized controlled trials (RCTs) when evaluating short-term efficacy and safety outcomes of edoxaban for VTE after total hip or knee arthroplasty. Nine RCTs with 4274 patients were involved in this meta-analysis. Edoxaban in the VTE group prevented the incidence of VTE and indicated valuable clinical efficacy. The incidence of adverse events (AEs) and adverse drug reactions (ADRs) in the edoxaban group was decreased than that in other groups. Edoxaban increased the incidence of all bleeding events. However, in the edoxaban group and other groups, there was no statistical difference between major bleeding events and clinically relevant non-major or minor bleeding events. Edoxaban subgroups included edoxaban 15 mg, edoxaban 30 mg and edoxaban 60 mg prevented the incidence of VTE. Edoxaban 30 mg and 60 mg group increased the risk of all bleeding events. Edoxaban 30 mg can increase the incidence of major bleeding events. There was no difference in clinically relevant non-major or minor bleeding events. Edoxaban 30 mg can decrease the incidence of AEs. Edoxaban was an efficacious and safe option to prevent and treat VTE in patients undergoing arthroplasty. However, we need further trials to explore edoxaban's long-term efficacy and safety.

Bioprosthetic vs. Mechanical Mitral Valve Replacement for Rheumatic Heart Disease in Patients Aged 50–70 Years

BackgroundRheumatic heart disease (RHD) is a critical problem in developing countries and is the cause of most of the cardiovascular adverse events in young people. In patients aged 50–70 years with RHD requiring mitral valve replacement (MVR), deciding between bioprosthetic and mechanical prosthetic valves remains controversial because few studies have defined the long-term outcomes.Methods1,691 Patients aged 50–70 years with RHD who received mechanical mitral valve replacement (MVRm) or bioprosthetic mitral valve replacement (MVRb) were retrospectively reviewed in Fuwai hospital from 2010 to 2014. Follow-up ended 31/12/2021; median duration was 8.0 years [interquartile range (IQR), 7.7–8.3 years]. Propensity score matching at a 1:1 ratio for 24 baseline features between MVRm and MVRb yielded 300 patient pairs. The primary late outcome was postoperative mid- to long-term all-cause mortality.ResultsTen-year survival after MVR was 63.4% in the MVRm group and 63.7% in the MVRb group (HR, 0.91; 95% CI, 0.69–1.21; P = 0.528). The cumulative incidence of mitral valve reoperation was 0.0% in the MVRm group and 1.2% in the MVRb group (HR, 0.92; 95% CI, 0.69–1.21; P = 0.530). The cumulative incidence of stroke was 5.5% in the MVRm group and 6.1% in the MVRb group (HR, 0.89; 95% CI, 0.67–1.18; P = 0.430). The cumulative incidence of major bleeding events was 3.3% in the MVRm group and 3.4% in the MVRb group (HR, 0.92; 95% CI, 0.70–1.22; P = 0.560).ConclusionsIn patients aged 50–70 years with RHD who underwent mitral valve replacement, there was no significant difference on survival, stroke, mitral valve reoperation and major bleeding events at 10 years. These findings suggest mechanical mitral valve replacement may be a more reasonable alternative in patients aged 50–70 years with rheumatic heart disease.

Trends of anticoagulant use and outcomes of patients with non-valvular atrial fibrillation: Findings from the RAFFINE registry

BackgroundThe management of non-valvular atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs). However, data regarding the effectiveness and safety of DOACs outside clinical trial settings are limited, and off-label dosing of DOACs has not been thoroughly investigated. MethodsWe examined the clinical outcomes of patients with non-valvular AF in the RAFFINE registry, a prospective registry of Japanese patients with AF who were followed-up for more than 3 years. ResultsAmong 3706 patients with non-valvular AF, 42.5% received warfarin and 44.7% received DOACs at baseline. The administration of DOACs increased annually. The mean CHADS2 and HAS-BLED scores were significantly higher in the warfarin group. The unadjusted all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group. The incidence of ischemic stroke/systemic embolism was not different between groups. After adjustment for baseline characteristics, the incidence of these events was not different between groups. Off-label dosing was performed for 32% of patients in the DOAC group, but this did not affect clinical outcomes. ConclusionsThe all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group than in the DOAC group. After adjustment, warfarin use was not associated with an increase in these events. Off-label dosing of DOACs is not rare and is not associated with reduced effectiveness. The impact of off-label dosing of each DOAC on clinical events should be assessed using a larger population.

Low risk of haematomas with intramuscular vaccines in anticoagulated patients: a systematic review with meta-analysis

IntroductionThe summary of product characteristics of vaccines administered intramuscularly, including the vaccine for coronavirus SARS-CoV-2 (COVID-19) and Influenza, warned for risks of bleeding in patients treated with oral anticoagulants. We aimed to estimate the incidence of major bleeding events in this setting and to compare these risks against other vaccination routes.MethodsThis systematic review included all prospective and retrospective studies enrolling anticoagulated patients that received intramuscular vaccination, published until December 2020 in CENTRAL, MEDLINE and EMBASE. The outcomes of interest were major bleeding and haematoma related with vaccination. The incidence of the outcomes was estimated through a random-effects meta-analysis using the Freeman-Turkey transformation. The results are expressed in percentages, with 95%-confidence intervals (95%CI), limited between 0 and 100%. When studies compared intramuscular vaccination vs. other route, the data were compared and pooled using random-effects meta-analysis. Risk ratios (RR) with 95%CI were reported.ResultsOverall 16 studies with 642 patients were included. No major bleeding event was reported. The pooled incidence of haematomas following vaccination (mostly against Influenza) in patients treated with oral anticoagulants (mostly warfarin; no data with DOACs / NOACs) was 0.46% (95%CI 0-1.53%). Three studies evaluated the intramuscular vs. subcutaneous route of vaccination. Intramuscular vaccines did not increase the risk of haematoma (RR 0.53, 95%CI 0.10-2.82) compared with subcutaneous route.ConclusionsIntramuscular vaccination in anticoagulated patients is safe with very low incidence of haematomas and the best available evidence suggests that using the intramuscular route does not increase the risk of haematomas compared with the subcutaneous route.

Efficacy and safety of app-based remote warfarin management during COVID-19-related lockdown: a retrospective cohort study.

This study aimed to explore the effectiveness, and safety of internet-based warfarin management during the pandemic. In this single-center retrospective cohort study, we compared the safety and efficacy of online warfarin management using a smartphone app (the Alfalfa app) versus conventional outpatient clinic management from January 1, 2020 to March 31, 2020. Patients in the online management group used the Alfalfa app to communicate coagulation test results and other relevant information to a doctor or clinical pharmacist, who then responded with the dose adjustment plan and the date of the next blood test. The outcomes examined were the time in therapeutic range (TTR), incidence of clinical events (i.e., bleeding events, thrombotic events, warfarin-related emergency department visits, and warfarin-related hospital admissions), and the distribution of international normalized ratio (INR) values. Data from 117 patients were analyzed in this study. TTR was significantly higher in the online group than in the offline group (61.0% vs. 39.6%, P < 0.01). Incidence of major bleeding events, thrombotic events, and warfarin-related hospital admissions were comparable between the online and offline groups. However, minor bleeds (5.3% vs. 28.3%, P < 0.01) and warfarin-related emergency department visits (1.8% vs. 23.3%, P = 0.02) were significantly fewer in the online group than in the offline group. The proportion of INR values in the therapeutic range (53.8% vs. 40.1%, P < 0.01) was significantly higher in the online group. Warfarin management using the Alfalfa app appears to be a safe and effective method for warfarin management when patients cannot physically visit hospitals for follow-up.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-021-02630-0.

Safety and efficacy of different anticoagulation regimens after left atrial appendage occlusion

This study examined the safety and efficacy of different anticoagulation regimens in patients with atrial fibrillation (AF) after left atrial appendage occlusion (LAAC) using the Watchman closure device. AF patients who underwent LAAC using the Watchman closure device in the Department of Cardiology, Jiangsu Taizhou People's Hospital between March 2018 and November 2019 were retrospectively enrolled in this study. Patients were divided into two groups according to different postoperative anticoagulant regimens. One group was treated with anticoagulant therapy alone [oral anticoagulant (OAC)/new OAC (NOAC) group] and the other was given NOACs combined with single antiplatelet therapy (SPAT) (NOAC + SAPT group). The incidences of ischemic stroke/transient ischemic attack (TIA), major bleeding events, all-cause mortality, and device-related thrombosis (DRT) were recorded. Furthermore, multivariate regression was used to analyze the factors associated with the occurrence of early DRT. A total of 160 patients, including 42 (51%) females, with a mean age of 69.13±6.14 years were enrolled in this study. The mean CHA2DS2-VASc score was 3.66±1.11 and the mean HAS-BLED score was 4.16±0.82. During the postoperative follow-up period, there were no significant differences in the incidence of ischemic stroke/TIA [hazard ratio (HR) =0.616; 95% confidence interval (CI): 0.056 to 6.818; P=0.693], major bleeding events (HR =0.520; 95% CI: 0.047 to 5.764; P=0.594) nor all-cause mortality (HR =0.579; 95% CI: 0.052 to 6.394; P=0.656) between the two groups. However, the incidence of early DRT was higher in the OAC/NOAC group compared to the NOAC + SAPT group [odds ratio (OR) =0.120; 95% CI: 0.015 to 0.984; P=0.048]. Multivariate regression confirmed that atrial blood stasis (OR =11.367; 95% CI: 1.394 to 92.687; P=0.023) and peri-device leak (OR =9.337; 95% CI: 1.623 to 53.727; P=0.012) were independent predictors of early DRT. Short-term NOAC + SAPT after LAAC did not significantly increase the incidence of major bleeding events, ischemic stroke/TIA, nor all-cause mortality compared to OAC/NOAC therapy. Not only was NOAC + SAPT therapy found to be safe and effective in short-term follow-up, but it also lowered the risk of early DRT.

Efficacy and safety of genotype-guided warfarin dosing versus non-genotype-guided warfarin dosing strategies: A systematic review and meta-analysis of 27 randomized controlled trials

ObjectiveTo evaluate the efficacy and safety of genotype-guided dosing (GD) strategies compared to non−genotype−guided dosing (non-GD) strategies for warfarin. MethodsDatabases were searched up to July 2021. Meta-analysis was conducted with the Review Manager software (version 5.4) and R (version 4.0.5). Risk ratio (RR), mean difference (MD), and 95% confidence intervals (CIs) were used. Subgroup analyses were conducted based on ethnicity and dosing regimen in non-GD group. Meta-regression was performed to evaluate the relation of covariates. This study is registered with PROSPERO (CRD42021245654). Results27 randomized controlled trials with a total of 9906 patients were included. The GD group resulted in a significantly improved time in therapeutic range compared with non-GD group in follow-up duration within 30 days (MD: 5.95, 95%CI: 2.41–9.22, P = 0.001) and beyond 30 days (MD: 4.93, 1.40–8.47, P = 0.006), time to the first therapeutic international normalized ratio (MD: −1.80, −2.69 - −0.92, P < 0.0001), and time to reach stable dose (MD: −5.08, −7.09 - −3.07, P < 0.00001), incidence of major bleeding events (RR: 0.50, 0.33–0.75, P = 0.0008), total bleeding events (RR: 0.83, 0.73–0.95, P = 0.006), and thromboembolism (RR: 0.69, 0.49–0.96, P = 0.03). No differences were found in stable dose achievement, minor bleeding events, over anticoagulation, and all-cause mortality. Four improved efficacy outcomes were observed in GD group compared with fixed dosing group. Only time to the therapeutic INR was shortened in GD group compared with clinical adjusted dosing group. The result showed no difference of safety outcomes between GD group and fixed dosing group whereas a decreased incidence of major bleeding events was observed when comparing to clinical adjusted dosing group. ConclusionGD strategy was superior to fixed dosing strategy in term of efficacy outcomes and comparable to fixed dosing strategy in safety outcomes. Clinical adjusted regimen could partly substitute the genotype-guided dosing strategy for efficacy in insufficient conditions, but the risk of major bleeding events should be monitored.