Indication For Oral Anticoagulation Research Articles

Time to oral anticoagulant reversal in intracranial hemorrhage with an emergency medicine pharmacist presence

PurposeIntracranial hemorrhage (ICH) is associated with high morbidity and mortality, with mortality rates up to 65%. Oral anticoagulants (OAC) are a major risk factor for ICH. Since these patients are usually diagnosed in the emergency department (ED), emergency medicine (EM) pharmacists can help ensure appropriate selection and delivery of medications in urgent situations including reversal agents for OAC-associated bleeding. The purpose of this study was to determine the impact EM pharmacist presence has on time to OAC reversal in patients presenting with an ICH. ProceduresThis was a retrospective, single-center cohort study evaluating time to reversal of OAC-associated ICH at a level one trauma center between November 2016 and September 2022. Patients 18 years or older who presented to the ED with an OAC-associated ICH and received at least one dose of an emergent reversal agent were included. Patients were excluded if their ICH was diagnosed at an outside facility, if they received emergent reversal agents for other indications, or if they had do not resuscitate orders upon admission. The primary outcome was time to administration of reversal agent with or without an EM pharmacist present, represented as median [interquartile range]. Secondary outcomes included hematoma expansion, hospital length of stay, intensive care unit LOS, and in-hospital mortality. ResultsOf the 157 patients evaluated, 83 met criteria for inclusion. Majority of patients presented with warfarin-associated ICH (55%) and the most common indication for OAC was atrial fibrillation (66%). The most common type of ICH was intracerebral hemorrhage (35%). The median time to emergent reversal agent administration was significantly shorter in the EM pharmacist group (50 min [31–65] vs. 85 min [51–121], p < 0.01). No significant differences in secondary outcomes existed. ConclusionsThe presence of an EM pharmacist at the bedside of patients who present to the ED with ICH was associated with a decrease in the time to OAC reversal by 36 min. Presence of an EM pharmacist was not associated with improved clinical outcomes for ICH in our study. Larger trials are warranted to determine whether the presence of an EM pharmacist is associated with improved functional and clinical outcomes in patients with OAC-associated ICH and whether time to newer reversal agents, other than 4F-PCC, has an effect on outcomes.

Bleeding and thrombotic risk of different antiplatelet regimens posttranscatheter edge-to-edge mitral valve repair in patients with an indication for oral anticoagulation: Results from an all-comers national registry.

Evidence-based recommendations for antithrombotic treatment in patients who have an indication for oral anticoagulation (OAC) after transcatheter edge-to-edge mitral valve repair (TEER) are lacking. To compare bleeding and thrombotic risk for different antithrombotic regimens post-TEER with MitraClip in an unselected population with the need for OACs. Bleeding and thrombotic complications (stroke and myocardial infarction) up to 3 months after TEER with mitraclip were evaluated in 322 consecutive pts with an indication for OACs. These endpoints were defined by the Mitral Valve Academic Research Consortium criteria and were compared between two antithrombotic regimens: single antithrombotic therapy with OAC (single ATT) and double/triple ATT with a combination of OAC and aspirin and/or clopidogrel (combined ATT). Collectively, 108 (34%) patients received single ATT, 203 (63%) received double ATT and 11 (3%) received triple ATT. Bleeding events occurred in 67 patients (20.9%), with access site related events being the most frequent cause (37%). Bleeding complications were observed more frequently in the combined ATT group than in the single ATT group: 24% versus 14% [p = 0.03, adjusted RR: 0.55 (0.3-0.98)]. Within the combined group, the bleeding risk was 23% in the double ATT and 45% in the triple ATT group. Thrombotic complications occurred in only three patients (0.9%), and all belonged to the combined ATT group. In patients with an indication for OACs, withholding of antiplatelet therapy post-TEER with Mitraclip was associated with a 45% reduction in bleeding and without a signal of increased thrombotic risk.

Abstract 15688: Association of Cytochrome P450 2C19 Polymorphism With Ischemic and Bleeding Risk in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Introduction: CYP2C19 isoenzymes of cytochrome P450 impact the effect of clopidogrel. Guidelines recommend clopidogrel in addition to oral anticoagulation (OAC) in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). This study aimed to evaluate the association of CYP2C19 polymorphism with ischemic and bleeding risk in patients with AF undergoing PCI. Methods: Patients with AF and an indication for OAC were included in this two-center prospective cohort study up to 3 days after PCI. Carriers of ≥1 loss of function (LOF) allele CYP2C19*2 were classified as poor metabolisers (PM). Carriers of ≥1 gain of function allele (GOF) were defined as rapid metabolisers (RM). Normal metabolisers (NM) were defined as absence of LOF and GOF alleles. Primary outcome was defined as death, myocardial infarction, or stroke (MACE) at 6 months ±2 weeks. Secondary outcome was defined as non-major clinically relevant (NMCR) or major bleedings. Results: 283 patients were included in the study. Median age was 78 (interquartile range, IQR 72-82) years old and 204 (72%) were males. All patients received treatment with clopidogrel and OAC. 73 (26%) were PM, 108 (38%) were NM and 102 (36%) RM. The primary ischemic outcome occurred in 22 (8%) and the secondary outcome in 38 (13%) patients. PM status did not significantly associate with primary ischemic outcome (PM: 6 [8.2%] vs. NM+RM: 16 [7.6%]; odds ratio, OR 1.09 [95% confidence interval 0.41-2.89], p=0.805). RM status did not significantly associate with bleeding (RM: 14 [13.7%] vs. PM+NM: 24 [13.3%]; OR 1.04 [0.51-2.12], p=1.00). Bleeding rates tended to be lower for patients with PM status (major, NMCR, or minor bleeding: PM 12 [28.7%] vs. NM+RM 84 [40.0%]; 0.61 [0.34-1.07], p=0.09). Conclusions: This pilot study of patients with oral anticoagulation for atrial fibrillation and clopidogrel after PCI ruled out, with 95% confidence, a ≥3-fold increase of ischemic risk for carriers of ≥1 loss of function allele CYP2C19*2 compared with non-carriers. This study was underpowered to detect less pronounced associations. LOF-carrier status might protect from bleeding.

Oral Anticoagulants after Heart Transplantation-Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants.

Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan-Meier estimator. DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients.

PO-03-133 BOTH OVERUSE AND UNDERUSE OF ORAL ANTICOAGULATION POST-ATRIAL FIBRILLATION ABLATION IN A LARGE HEALTHCARE SYSTEM

Guidelines recommend that decisions regarding oral anticoagulation (OAC) post ablation for atrial fibrillation (AF) should be based solely on the patient’s stroke risk profile, regardless of the outcomes of the procedure. The adherence to this recommendation in clinical practice has not been examined. To provide real-world data about adherence to anticoagulation guidelines after AF ablation. We included patients undergoing AF ablation in one of 8 hospitals of Northwell Health between 2014 and 2022. We excluded patients without continuous OAC for at least 2 months post-ablation and without a complete 3- and 12-month follow-up. Adherence to OAC guidelines was defined as continuing OAC for males with CHA2DS2-VASc≥2 and females with CHA2DS2-VASc≥3 and discontinuing OAC for the rest. A subgroup analysis of patients based on their CHA2DS2-VASc scores (0, 1, 2, and ≥3) was performed. Exploratory clinical endpoints included AF recurrence, stroke/transient ischemic attack, bleeding events, and all-cause mortality. Out of 900 patients, 69 (7.7%) and 187 (20.1%) discontinued OAC at 3- and 12-months post-ablation, respectively (Figure 1). Among patients who discontinued OAC at 12 months, 91 (48.6%) met indication for OAC. In contrast, among those without OAC indication, 36 (54.5%) patients remained on OAC at 12 months. Patients who discontinued OAC were younger with mostly paroxysmal AF and fewer comorbidities; lending to lower CHA2DS2-VASc scores (all p< 0.001). Specifically, 64.7%, 46.6%, 22.3% and 10.6% of patients with CHA2DS2-VASc of 0, 1, 2, and ≥3 respectively, discontinued OAC at 12 months (Table 1). Among those who discontinued OAC, 6 (13.0%), 32 (18.5%), 48 (13.2%), and 106 (10.5%) had AF recurrence and 0 (0%), 1 (2.3%), 0 (0%), and 1 (2.2%) had a stroke in CHA2DS2-VASc 0, 1, 2, and ≥3 groups, respectively. The most common reasons for discontinuation were patient preference, contraindications, and physician-patient shared decision-making. OAC was discontinued in approximately 20% of all patients undergoing catheter ablation at 1 year. Of these, roughly half had an ongoing indication for OAC. On the other hand, approximately half of patients with very low thromboembolic risk remain on OAC despite no evidence of AF recurrence.Tabled 1Table 1CHA2DS2-VASc0 (n=34)1 (n=133)2 (n=215)≥3 (n=518)Anticoagulation off (%)64.746.622.310.6AF Recurrence (%)17.624.122.520.6Stroke/TIA (%)01.01.22.2All-cause death (%)00.80.92.7Any bleeding (%)00.80.91.3 Open table in a new tab

Family Physician Prescribing Practices and Perspectives on Shared Decision-Making Regarding the Use of Oral Anticoagulants for Stroke Prevention in Patients 75 Years or Older With Atrial Fibrillation.

Atrial Fibrillation (AF) is common in older adults, yet guideline-recommended oral anti-coagulants (OACs) for stroke prevention are underused in this population. With a growing population of older adults at risk of AF seeking primary care, the objective of the study was to determine the management practices and perspectives of family physicians on the initiation of OACs for stroke prevention in AF patients 75 years or older, including their engagement of patients in shared decision-making. This was an online survey of family physicians affiliated with a Primary Care Network in Alberta, Canada. Patient's risk (of falls, bleeding, or stroke) was the most common factor (17/20, 85%) physicians considered when deciding to initiate OAC in older adult patients with AF. Physicians used the CHADS2VASC (13/14, 93%) and HASBLED (11/15, 73%) tools to determine stroke and bleeding risks, respectively. Majority (11/15, 73%) of the physicians agreed that they feel confident initiating OAC for AF patients ≥75, while 20% (3/15) were neutral. All physicians agreed that their patients participated in shared decision-making to initiate OAC for stroke prevention. Family physicians strongly consider patient risks and utilize risk-assessment tools when initiating OAC in older adults with AF. Despite all physicians reporting the use of shared decision-making and that their patients were educated on the indications for OAC, confidence in initiating treatment was variable. Further exploration into factors impacting physician confidence is needed.

757 DIRECT ORAL ANTICOAGULANTS OR VITAMIN K ANTAGONISTS IN AFTER TAVR

Abstract Background Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein thromboembolism. However, the optimal type of OAC strategy (direct oral anticoagulants, DOACs, or vitamin K antagonists, VKA) is still unclear in this setting. Method We performed systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies reporting either all-cause mortality, major/life-threatening bleeding or stroke events. Results Ten observational studies and one randomized controlled trial (RCT), including 29,333 patients, were eligible for inclusion. Compared to VKA, DOACs use after TAVR was associated with a modest but significantly lower rates of all-cause mortality (RR 0.88; 95% CI: 0.78-0.99, p-value 0.04). Total stroke events (RR 0.97; 95% CI: 0.76-1.23, p-value 0.79) and major/life-threatening bleeding (RR 0.94; 95% CI: 0.70-1.27, p-value 0.69) were comparable among the two treatments. In the following sensitivity analysis including observational studies only, results in terms stroke events were consistent (RR 1.00;95% CI: 0.75-1.34, p-value 0.99) . However, the overall mortality was comparable between the two treatments (RR 0.88; 95% CI: 0.77-1.00, p-value 0.99), while major/life-threatening bleeding occurred less in the DOACs group (RR 0.80; 95% CI: 0.68-0.94, p-value 0.006). Conclusion Considering the totality of published evidence in TAVR patients with a concomitant indication for OAC, DOACs use was associated with reduced all-cause mortality and comparable major/life-threatening bleeding and stroke events compared to VKA.

Antithrombotic Treatment and Its Association with Outcome in a Multicenter Cohort of Transcatheter Edge-to-Edge Mitral Valve Repair Patients

Transcatheter edge-to-edge mitral valve repair (TEER) has become established as a safe and efficacious therapy for severe mitral regurgitation (MR) in high-risk patients. Despite its widespread use, postprocedural antithrombotic therapy (ATT) still to date is based on local expertise rather than evidence. In a multicenter, observational cohort study, 646 consecutive patients undergoing TEER were enrolled; 609 patients were successfully treated and antithrombotic therapy analyzed; 449 patients (73.7%) were previously treated with oral anticoagulants (OAC) due to the high prevalence of atrial fibrillation (459/609, 75.4%). Postprocedural ATT in patients previously treated with OAC consisted of no additional, additional single (SAPT) or dual antiplatelet therapy (DAPT) in 146/449 (33.6%), 248/449 (55.2%) and 55/449 (12.2%), respectively. There were 234/449 (52.1%) patients treated with vitamin-k antagonists (VKA) and 215/449 (47.9%) with nonvitamin-k antagonist oral anticoagulants (NOAC). One hundred sixty patients (26.3%) had no prior indication for OAC and were predominantly treated with DAPT (132/160, 82.5%). Use of SAPT (17/160, 10.6%) and no APT (11/160, 6.9%) was marginal. No statistically significant differences in terms of in-hospital mortality or the rate of major adverse cardiac and cerebrovascular events (MACCE) between the different antithrombotic therapy regimens were observed. Multiple Cox regression analysis showed a statistically significant decreased risk for all-cause mortality after a median follow-up of 419 days for OAC monotherapy (HR 0.6, 95%-CI 0.5-0.9, p = 0.04). This study provides evidence for a more favorable long-term outcome of OAC monotherapy in patients with an indication for OAC and reiterates the urgent need for randomized controlled trials on the optimal antithrombotic treatment of TEER patients.

ORal anticoagulation risks late aortic intervention in Conservatively managed type B Aortic dissection (ORCA study).

Single-center retrospective cohort study to evaluate the impact of oral anticoagulation (OAC) on long-term outcomes of conservatively managed acute type B aortic dissection. Clinical and morphological data of eligible patients from a high-volume vascular centre from 1 January 2003 through 31 December 2020 were evaluated. Patients were excluded for: type A or non-A-non-B dissection, isolated abdominal dissection, intramural haematoma and connective tissue disease. The primary outcome was freedom from late aortic events (intervention, rupture and mortality). Secondary outcomes included spinal cord ischaemia, bleeding, reno-visceral artery occlusion, ilio-femoral intervention, dissection propagation, aortic growth, aortic remodelling, deterioration of false lumen thrombosis as well as 30-day and overall mortality. Time to event was analysed using multivariable Cox proportional hazard models with OAC as time-varying covariate and mortality as a competing risk. The impact of OAC was adjusted for potential confounding factors. A total of 69 patients [50 males, median age 65 (interquartile range: 58-72) years] were enrolled. The median follow-up was 49.3 (28-92) months. A total of 47 patients (68%) received OAC at any time throughout the follow-up for a median length of 26 (11-61) months. Late aortic events occurred in 28 patients (41%) including intervention (n = 27, 39%) and rupture (n = 1, 1%). OAC was associated with more late aortic events (hazard ratio 3.94, 95% confidence interval 1.06-14.6, P = 0.040). Secondary outcomes were not associated with OAC. Our data suggest a relation of OAC therapy with an increased risk for late aortic interventions. Type B aortic dissection should not be the primary indication for OAC and patients with OAC for other indications require frequent follow-up imaging.

Early in-hospital discontinuation of aspirin following coronary stent implantation in patients with indication for direct oral anticoagulation

Abstract Background and purpose 5–10% of patients undergoing percutaneous coronary intervention (PCI) have an indication for oral anticoagulation (OAC). Triple therapy, i.e. anticoagulation plus dual antiplatelet therapy, is associated with a high bleeding rate. Discontinuation of aspirin while continuing direct OAC (DOAC) and a P2Y12 inhibitor (so-called dual therapy) after PCI, was investigated in four randomized trials demonstrating a reduction in bleeding without significant differences in ischemic events. Since randomization was performed several days after the index PCI, these trials allowed for a short period of triple therapy. Whether exclusive procedural application of aspirin and early discontinuation of aspirin at the first postprocedural day is safe, is unknown and was the scope of this work. Methods and results We retrospectively analysed 3613 patients (4564 PCIs) treated from 2017 to 2020 at our centre. 871 (24.1%) patients (1059 PCIs, 23.2%) had an indication for OAC. In 284 PCIs with stenting, patients received DOAC (71.8% Rivaroxaban, 25.7% Apixaban, 1.8% Dabigatran, 0.7% Edoxaban) + P2Y12 inhibitor (100% clopidogrel) + aspirin only at the day of procedure (group 1). In 52 PCIs with stenting, patients received DOAC (59.6% Rivaroxaban, 34.6% Apixaban, 1.9% Dabigatran, 3.9% Edoxaban) + P2Y12 inhibitor (100% clopidogrel) + 100 mg aspirin/d at ≥1 postprocedural day (group 2). Based on our local patient database, we analysed the rate of ischemic events (myocardial infarction, stent thrombosis, stroke/transient ischemic attack (TIA), pulmonary/systemic embolism (PE/SE), deep vein thrombosis) as well as major and minor bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) criteria during hospitalisation. Data are presented as mean±standard deviation or median (range). Baseline characteristics were similar (group 1 vs. group 2: 74.3% vs. 73.1% male, age 75.9±8.5 vs. 74.3±9.3 years, atrial fibrillation 91.2% vs. 88.5%), except previous PE (3.5% vs. 11.5%; p=0.024), type of preprocedural DOAC (Rivaroxaban 52.5% vs. 34.6%; p=0.023) and creatinine clearance (62.4±19.7 vs. 68.9±20.3 ml/min; p=0.029). Median duration of postprocedural hospitalisation was 1 day for both groups (0–20 days vs. 1–21 days). In both groups, one TIA occurred (p=0.292), there were no other ischemic events. 36 (12.7%) bleeding events occurred in group 1 and 11 (21.2%) in group 2 (p=0.126). A subgroup analysis of cases being hospitalised for ≥2 postprocedural days (group 1: 87 cases, median 4 (2–20) days; group 2: 20 cases, median 2 (2–21) days) found no ischemic events and no difference regarding bleeding events (34.5% vs. 45.0%; p=0.443). Conclusions Exclusive procedural application of aspirin and start of dual therapy at the first postprocedural day appears safe regarding ischemic events in a real-world population. Nearly ¼ of patients undergoing PCI had an indication for OAC, which is much more frequent than previously reported. Funding Acknowledgement Type of funding sources: None.

Association of coagulation markers and antiphospholipid antibodies with ischemic and bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Antiphospholipid antibodies and other coagulation markers are associated with ischemic risk in patients with coronary artery disease without oral anticoagulation (OAC). Aim To assess the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Patients and methods In this prospective single center observational cohort study, patients with AF and an indication for OAC were enrolled after PCI. Dilute Russell's viper venom time (DRVVT) was used to determine lupus anticoagulants (LA) in direct OAC-free plasma. Anti-cardiolipin IgG (aCL), IgM and anti-beta2GP-1-IgG (aβ2GP1) were analyzed by enzyme linked immunosorbent assay (ELISA). Fibrinogen C (FIBC), d-dimers and prothrombin fragments 1 and 2 (PF1+2) were measured in citrated plasma. Immature platelet fraction (IPF [%]) and absolute (IPF abs. [103/μl]) were measured in EDTA-blood. The primary ischemic outcome was defined as time to major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to the International Society of Thrombosis and Haemostasis (ISTH) and the Bleeding Academic Research Consortium (BARC). Results 158 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range, IQR 72–82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. All Patients were treated with clopidogrel and OAC, 145 (92%) in addition with acetylsalicylic acid (ASA). 32 patients (20%) had ≥1 antiphospholipid antibody (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). D-dimers were elevated in 74 patients (47%), FIBC was increased in 40 (25%) and PF1+2 in 68 patients (43%). IPF [%] was elevated in 28 (18%) and IPF abs. [103/μl] in 11 (7%). The presence of aPL was neither significantly associated with MACE, nor with bleeding risk. Elevated d-dimers were significantly associated with higher risk for MACE (HR=5.1, 95% CI [1.1; 23.4], p=0.04), major ISTH bleeding events (HR= 6.9, 95% CI [1.5; 30.8], p=0.01) and BARC bleeding type 3 or 5 (HR=6.4, 95% CI [1.4; 28.7], p=0.02). Increased levels of FIBC were associated with risk of MACE (HR= 3.6, 95% CI [1.1; 12.0], p=0.03 (Table 1). Conclusion In patients with AF undergoing PCI, high levels of d-dimers and fibrinogen C indicate an increased ischemic risk. Elevated d-dimers are associated with higher risk for bleeding. aPL positivity was not significantly associated with outcome possibly due to low sample size. A combined panel of biomarkers might be suitable to assess ischemic and bleeding risk in patients with AF following PCI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine, Freiburg

Thrombelastography Compared with Multiple Impedance Aggregometry to Assess High On-Clopidogrel Reactivity in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

Background: High on-clopidogrel platelet reactivity (HPR) following percutaneous coronary intervention (PCI) is associated with increased ischemic risk. It is unclear whether conventional definitions of HPR apply to patients with concomitant oral anticoagulation (OAC). This study aimed to compare the performance of multiple platelet aggregometry (MEA) and thrombelastography (TEG) to detect HPR in patients with atrial fibrillation (AF) and indication for an OAC. Methods: In this observational single-center cohort study, MEA and TEG were performed in patients with AF with an indication for OAC on day 1 to 3 after PCI. The primary outcome was HPR as assessed by MEA (ADP area under the curve ≥ 46 units [U]) or TEG (MAADP ≥ 47 mm), respectively. The secondary exploratory outcomes were a composite of all-cause death, myocardial infarction (MI) or stroke and bleeding, as defined by the International Society on Thrombosis and Hemostasis, at 6 months. Results: Platelet function of 39 patients was analyzed. The median age was 78 (interquartile range [IQR] was 72–82) years. 25 (64%) patients were male, and 19 (49%) presented with acute coronary syndrome. All patients received acetylsalicylic acid and clopidogrel prior to PCI. Median (IQR) ADP-induced aggregation, MAADP, TRAP-induced aggregation, and MAthrombin were 9 (6–15) U, 50 (43–60) mm, 54 (35–77) U and 65 (60–67) mm, respectively. The rate of HPR was significantly higher if assessed by TEG compared with MEA (25 [64%] vs. 1 [3%]; p < 0.001). Within 6 months, four (10%) deaths, one (3%) MI and nine (23%) bleeding events occurred. Conclusion: In patients with AF undergoing PCI, the rates of HPR detected by TEG were significantly higher compared with MEA. Conventional cut-off values for HPR as proposed by consensus documents may need to be re-evaluated for this population at high ischemic and bleeding risk. Further studies are needed to assess the association with outcomes.

Oral anti-coagulant treatment patterns in atrial fibrillation patients diagnosed with cancer: A Danish nationwide cohort study.

Data on the use of oral anti-coagulants (OAC) for stroke prevention in cancer patients with atrial fibrillation (AF) are sparse. Nationwide cohort study of patients with AF (2012-2018) and an indication for OAC who were diagnosed with cancer at least one year later (N=12 756). We identified treatment with OAC at cancer diagnosis and the following year and described the incidence of discontinuing or switching between warfarin and direct oral anti-coagulants (DOACs). We also described baseline characteristics associated with OAC non-persistence. One third of the cancer patients received no OAC therapy, whereas 42% received warfarin and 24% received DOAC treatment. Switching incidence between OACs was higher for those receiving warfarin treatment (8.6%) than DOAC treatment (1.7%) within one year. Treatment discontinuation was 61% for warfarin and 26% for DOAC. Females were less likely to discontinue DOAC than males (ratio 0.77, 95% confidence interval: 0.66, 0.90). Increasing cancer stage was associated with discontinuation of DOAC, but not warfarin. OAC for stroke prevention in AF was used by two thirds of patients with newly diagnosed cancer. Switching between OACs and discontinuation was more common for warfarin than DOAC, and females had higher persistence with DOACs.

Antithrombotic Therapy after Transcatheter Aortic Valve Replacement.

ABSTRACTTranscatheter aortic valve replacement (TAVR) is a treatment option for patients with asymptomatic severe aortic stenosis who are candidates for a bioprosthesis across the entire spectrum of risk. TAVR carries a risk for thrombotic and bleeding events, focusing on the importance of defining the optimal antithrombotic regimen. Patients undergoing TAVR are mostly elderly and have many comorbidities such as atrial fibrillation (AF) requiring oral anticoagulants (OACs) or coronary artery disease requiring antiplatelet agents. After TAVR among patients without baseline indications for OAC, recent data suggest dual-antiplatelet therapy is associated with an increased risk for bleeding events, particularly early postprocedure compared with single-antiplatelet therapy with aspirin. The risk of leaflet thrombosis in patients undergoing TAVR raised concern about the use of OAC in patients without an initial indication for anticoagulation therapy. Although it showed effectiveness in modulating thrombus formation at the valve level, the bleeding hazard has shown to be unacceptably high, and the net benefit of combining antiplatelet and OAC therapy is unproven. For patients with indications for the use of long-term OAC, such as those with AF, adding antiplatelet therapy increases bleeding events. A favorable effect of new OAC agents over Vitamin K antagonists is debatable. Overall, single-antiplatelet therapy and OAC appear to be reasonable strategies in patients without and with indications for concurrent anticoagulation, respectively. This article aims to review the available published studies and recommendations in the literature regarding the use of antithrombotic therapy post-TAVR.

Anticoagulation management in adult patients with congenital heart disease: a narrative review

With improvements in treatment of congenital heart disease more paediatric patients are surviving with palliative or corrective interventions during childhood, thus becoming adults with congenital heart disease (ACHD). Overall, the ACHD population is at a higher risk of arrhythmias and stroke. The abnormal structure and function of their corrected hearts suggests that in addition to established stroke risk factors, such as prior stroke or older age, additional stroke risk factors need to be considered to determine the risk and establish the indication for oral anticoagulation (OAC) in ACHD patients. In structurally normal hearts non-vitamin-K oral anticoagulants (NOACs) offer at least equal stroke prevention with a better safety profile compared to vitamin K antagonists (VKA) in patients with atrial fibrillation (AF) or pulmonary embolism. Current guidelines recommend NOACs in ACHD patients with simple lesions and indication for OAC, while there is less certainty about their safety in ACHD patients with moderate or complex congenital heart disease such as patients with transposition of the great arteries (TGA) after atrial switch operation (Senning or Mustard operation), Fontan circulation or congenital corrected transposition of the great arteries (ccTGA). This review summarises the available evidence characterising stroke risk in patients with ACHD and the use of anticoagulants and interventional therapies to reduce that risk.

Abstract 11338: On-Clopidogrel Platelet Reactivity in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention and Association with Patient Characteristics

Introduction: On-clopidogrel platelet reactivity (PR) is associated with thrombotic and bleeding risk in patients undergoing percutaneous coronary intervention (PCI). Patient-related factors affect the level of PR. Patients with atrial fibrillation (AF) undergoing PCI are treated concomitantly with oral anticoagulants (OAC) potentially interacting with platelet function. This study aimed to investigate the association of PR with demographic and clinical characteristics in these patients. Methods: In this single-centre prospective observational cohort study, patients with AF with an indication for OAC were enrolled during hospitalization after PCI with clopidogrel. TRAP- and ADP- induced PR (TRAP 32 μM, ADP 6.4 μM) were assessed by multiple electrode aggregometry. ADP-induced PR was normalized to TRAP-induced PR (r-ADP-agg). Results: 159 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range, IQR 72-82), 112 (70%) were male and 39 (25%) presented with ACS. 68 (43%) presented with chronic kidney disease (CKD), defined as GFR&lt;60. 54 (34%) patients received apixaban, 6 (4%) dabigatran, 18 (11%) edoxaban, 74 (47%) rivaroxaban and 4 (3%) marcumar. 128 (81%) patients received clopidogrel loading. Median ADP-induced PR was 12 U (IQR 6-17); median r-ADP-agg was 24% (IQR 14-39). ADP-induced PA is significantly correlated with age (r=-0.22; p=0.035) and platelet count (r=0.22; p=0.006). Compared to the patients without CKD,patients with CKD had a significantly lower ADP-induced PA (median 8 [IQR 10] vs. median 13 [IQR 10]; p&lt;0.001) and r-ADP-agg. (median 20 [IQR 25] vs median 28 [IQR 24]; p=0.003).In a multivariable linear regression, ADP-induced PR was significantly associated with age (r=-0.177, CI:-0.481 to -0.018, p=0.035), immature platelet count (r=0.178, CI: 0.003 to 0.729, p=0.048), and diabetes mellitus (r=0.21, CI: 1.192 to 9.087, p=0.011). CKD was associated with both: lower ADP-PR (r=-0.262, CI:-9.962 to -2.396, p=-0.002) and lower r-ADP-agg (r=-0.253, CI:-9.962 to -2.396, p=0.003). Conclusions: In this patient cohort the association of on-clopidogrel PR as assessed by multiple electrode aggregometry with patient related factors was weak and most pronounced for chronic kidney disease.

Antithrombotic Therapy After Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is a treatment option for symptomatic patients with severe aortic stenosis who are candidates for a bioprosthesis across the entire spectrum of risk. However, TAVR carries a risk for thrombotic and bleeding events, underscoring the importance of defining the optimal adjuvant antithrombotic regimen. Antithrombotic considerations are convoluted by the fact that many patients undergoing TAVR are generally elderly and present with multiple comorbidities, including conditions that may require long-term oral anticoagulation (OAC) (eg, atrial fibrillation) and antiplatelet therapy (eg, coronary artery disease). After TAVR among patients without baseline indications for OAC, recent data suggest dual-antiplatelet therapy to be associated with an increased risk for bleeding events, particularly early postprocedure, compared with single-antiplatelet therapy with aspirin. Concerns surrounding the potential for thrombotic complications have raised the hypothesis of adjunctive use of OAC for patients with no baseline indications for anticoagulation. Although effective in modulating thrombus formation at the valve level, the bleeding hazard has shown to be unacceptably high, and the net benefit of combining antiplatelet and OAC therapy is unproven. For patients with indications for the use of long-term OAC, such as those with atrial fibrillation, the adjunctive use of antiplatelet therapy increases bleeding. Whether direct oral anticoagulant agents achieve better outcomes than vitamin K antagonists remains under investigation. Overall, single-antiplatelet therapy and OAC appear to be reasonable strategies in patients without and with indications for concurrent anticoagulation. The aim of the present review is to appraise the current published research and recommendations surrounding the management of antithrombotic therapy after TAVR, with perspectives on evolving paradigms and ongoing trials.

Safety and Efficacy of Different Antithrombotic Strategies after Transcatheter Aortic Valve Implantation: A Network Meta-Analysis.

The optimal pharmacological therapy after transcatheter aortic valve implantation (TAVI) remains uncertain. We compared efficacy and safety of various antiplatelet and anticoagulant approaches after TAVI by a network meta-analysis. A total of 14 studies (both observational and randomized) were considered, with 24,119 patients included. Primary safety endpoint was the incidence of any bleeding complications during follow-up. Secondary safety endpoint was major bleeding. Efficacy endpoints were stroke, myocardial infarction, and cardiovascular mortality. A frequentist network meta-analysis was conducted with a random-effects model. The following strategies were compared: dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), oral anticoagulation (OAC), and OAC + SAPT. The mean follow-up was 15 months. In comparison to DAPT, SAPT was associated with a 44% risk reduction of any bleeding (odds ratio [OR]: 0.56 [95% confidence interval, CI: 0.39-0.80]). SAPT was ranked as the safest strategy for the prevention of any bleeding (p-score: 0.704), followed by OAC alone (p-score: 0.476) and DAPT (p-score: 0.437). Consistent results were observed for major bleeding. The incidence of cardiovascular death and secondary ischemic endpoints did not differ among the tested antithrombotic approaches. In patients with indication for long-term anticoagulation, OAC alone showed similar rates of stroke (OR: 0.92 [95% CI: 0.41-2.05], p = 0.83) and reduced occurrence of any bleeding (OR: 0.49 [95% CI: 0.37-0.66], p < 0.01) versus OAC + SAPT. The present network meta-analysis supports after TAVI the use of SAPT in patients without indication for OAC and OAC alone in those needing long-term anticoagulation.

Rates of rebleeding, thrombosis and mortality associated with resumption of anticoagulant therapy after anticoagulant-related bleeding.

BACKGROUND:Data on resuming oral anticoagulants (OACs) after bleeding are primarily from studies involving patients given warfarin, with few data on direct OACs (DOACs). We aimed to characterize prescribing patterns for OACs after OAC-related bleeding and compare the rates of bleeding, thrombosis and mortality in patients who resumed either type of OAC with those who did not.METHODS:We conducted a population-based cohort study of adults aged 66 years or older who were admitted to hospital for bleeding while receiving OACs from Apr. 1, 2012, to Mar. 31, 2017, using linked administrative health databases from Ontario. We used competing risk methods to calculate cause-specific adjusted hazard ratios (HRs) for thrombosis, bleeding and mortality with resumption of OACs adjusted as a time-varying covariate. We determined time to OAC resumption using the Kaplan–Meier method.RESULTS:We included 6793 patients with gastrointestinal (n = 4297, 63.3%), intracranial (n = 805, 11.9%) or other bleeding (n = 1691, 25.0%). At cohort entry, 3874 patients (57.0%) were prescribed warfarin and 2919 patients (43.0%) were prescribed a DOAC. The most common indication for OAC was atrial fibrillation (n = 5557, 81.8%), followed by venous thromboembolism (n = 1367, 20.1%). Oral anticoagulants were resumed in 4792 patients (70.5%) within 365 days of the index bleed. The median time to resumption was 46 (interquartile range 6–550) days. We found that resuming OAC was associated with reduced rates of thrombosis (adjusted HR 0.60, 95% confidence interval [CI] 0.50–0.72) and mortality (adjusted HR 0.54, 95% CI 0.48–0.60), and an increased rate of rebleeding (adjusted HR 1.88, 95% CI 1.64–2.17).INTERPRETATION:We found that resuming OAC is associated with a reduction in thrombosis and mortality but an increase in bleeding. Randomized controlled trials that evaluate the net benefit of strategies for resumption of OAC after a bleeding event are warranted.

Efficacy and safety of antithrombotic therapy with non-vitamin K antagonist oral anticoagulants after transcatheter aortic valve replacement: a systematic review and meta-analysis.

Objective:A meta-analysis was performed to compare the efficacy and safety of antithrombotic therapy with non-vitamin K antagonist oral anticoagulants (NOACs) versus standard care in patients after successful transcatheter aortic valve replacement (TAVR).Methods:A systematic search of PubMed, Cochrane Central Register of Controlled Trials, and EMBASE databases and ClinicalTrials.gov website (through 21 October 2020) was performed. Risk ratios (RRs) with 95% confidence intervals (CIs) for all outcomes were calculated using random-effects models.Results:Twelve studies (two studies were randomized controlled trials) comprising 6943 patients were included (5299 had indications for oral anticoagulation (OAC) and 1644 had none). No significant differences were found between NOACs and the standard care in the incidences of all stroke, a composite endpoint, and major/life-threatening bleeding. NOACs were associated with lower all-cause mortality than vitamin K antagonists (VKAs) in post-TAVR patients with indications for OAC after more than 1 year of follow-up [RR = 0.64; 95% CI, (0.42, 0.96); p = 0.03], whereas NOACs exhibited poor outcomes than antiplatelet therapy (APT) in patients without indications for OAC [RR = 1.66; 95% CI, (1.12, 2.45); p = 0.01]. In the prevention of valve thrombosis, NOACs and VKAs were not significantly different in patients with indications for OAC [RR = 0.66; 95% CI, (0.24, 1.84); p = 0.43], whereas NOACs were better than APT in patients without indications for OAC [RR = 0.19; 95% CI, (0.04, 0.83); p = 0.03].Conclusions:In patients with indications for OAC, post-TAVR antithrombotic therapy with NOACs was more favorable due to its lower all-cause mortality after more than 1 year of follow-up. In those without indications for OAC, NOACs presented poorer outcomes due to its higher all-cause mortality.