Higher Rates Of Major Bleeding Research Articles

Effect of Frailty on the Long-Term Prognosis of Elderly Patients with Acute Myocardial Infarction.

To investigate the effect of frailty on the long-term prognosis of elderly patients with acute myocardial infarction (AMI). The data of 238 AMI patients (aged ≥75 years) were retrospectively reviewed. They were divided into two groups according to the Modified Frailty Index (mFI): frailty group (mFI≥0.27, n=143) and non-frailty group (mFI<0.27, n=95). The major adverse cardiovascular and cerebrovascular events (MACEs) and Kaplan-Meier survival curves of the two groups were compared. Multivariate Cox regression analysis was used to identify the risk factors for MACEs. The frailty group showed a significantly older age as well as a higher N-terminal proB-type natriuretic peptide level, Global Registry of Acute Coronary Events score, and CRUSADE bleeding score compared with the non-frailty group (P<0.05). A significantly greater proportion of patients with combined heart failure, atrial fibrillation, comorbidity, and activities of daily living score of <60 was also observed in the frailty group compared with the non-frailty group (P<0.05). At 36 months after AMI, the frailty group vs the non-frailty group showed a significantly poorer survival (log-rank P=0.005), higher incidence of MACEs (50.35 vs 29.47, P=0.001), higher overall mortality rate (20.98% vs 7.37%, P=0.006), higher 30-day mortality rate (13.99% vs 5.26%, P=0.033), higher major bleeding rate (14.69% vs 5.26, P=0.018), and lower repeat revascularization rate (2.10% vs 8.42%, P=0.03). Frailty, type 2 diabetes, and N-terminal proB-type natriuretic peptide ≥1800 pg/mL were independent risk factors for MACEs. Frailty is an independent risk factor affecting the long-term prognosis of elderly patients with AMI.

Venous Thromboembolism Outcomes Among Cancer and Non-Cancer Patients Managed with Patient-Centric Guideline-Driven Protocol

Purpose/Introduction: Patients with cancer and venous thromboembolism (VTE) have higher complication rates including thrombosis recurrence and bleeding. Real world prospective clinical outcome estimates of VTE management comparing cancer and non-cancer patients are limited. To assess VTE recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB) in patients with cancer and without cancer, the prospective Mayo Clinic Thrombophilia Clinic Registry was analyzed. Methods: Upon recruitment, consecutive patients with confirmed acute VTE (03/01/2013 - 04/30/2023) were treated in a standardized, guideline-sanctioned, protocol driven strategy incorporating shared patient-decision making. Patients were divided into groups based on cancer status. After enrollment, patients were actively followed at 3 month intervals, in person whenever feasible, by mailed questionnaire or scripted phone interview to assess vital status, medication compliance, VTE recurrence, major bleeding and CRNMB. Results: Over the study time-frame, 2,064 patients (53.8% male, 46.2% female) with a cancer and 2,647 patients (54.9% male, 45.1% female) without cancer were enrolled. The most common cancers were gastrointestinal (n=423, 20.5%), pancreatic (n=287, 13.9%), genitourinary (n=198, 9.6%), hematologic (n=171, 8.3%), and lung cancer (n=170, 8.2%). Patients with cancer were older, had lower weight and lower platelet counts compared to non-cancer patients (Table1). Pulmonary embolism (PE, 52.6% vs 43.7%, p&amp;lt;0.001), upper extremity DVT (9.1% vs 6.0%, p&amp;lt;0.001), and splanchnic DVT (11.1% vs 6.9%, p&amp;lt;0.001) were more frequent among cancer patients. In contrast, leg DVT was more frequent among non-cancer patients (65.4% vs.47.2%, p&amp;lt;0.001). While mean duration of anticoagulation was similar between groups, notable differences in 3 month and &amp;gt; 9 month durations were evident as were initial anticoagulant choices (Table 1). Despite a well-organized protocol driven and guideline sanctioned management strategy, patients with active cancer experienced a 2.2-fold higher rate of VTE recurrence (p&amp;lt;0.001) and a 1.8 fold higher rate of major bleeding (p&amp;lt;001) compared to non-cancer patients (Table 2). CRNMB rates did not differ by cancer status. Conclusions: In this large prospective, guideline-driven and patient-centric registry of VTE management, patients with cancer had significantly higher rate of VTE recurrence and major bleeding, compared to non-cancer patients. These data provide important estimates for power calculations for future randomized trials of VTE treatment.

Abstract 14237: Anticoagulation Strategies After Transcatheter Aortic Valve Implantation in Patients Without an Indication of Oral Anticoagulants, Network Meta Analysis of Randomized Controlled Trials

Introduction. Transcatheter aortic valve implantation (TAVI) is currently the mainstay treatment for aortic valve diseases, yet postoperative anticoagulation strategies after TAVI is still debatable. Thus, we aim to investigate the safety and efficacy of direct oral anticoagulants (DOACs) vs. single-antiplatelet therapy (SAPTs) vs. dual-antiplatelet therapy (DAPT) vs. Vitamin K antagonists (VKAs) in patients undergoing TAVI and without an indication of OACs. Methods: PubMed, Web of Science, Scopus, and Embase were systematically searched up to December 2022. A frequentist network meta-analysis has been conducted using a random-effects model calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: We included 9,087 patients from 11 studies. Compared to DOACs, DAPT, SAPT, and VKAs were associated with significantly lower odds for short-term all-cause mortality (OR: 0.62; 95% CI [0.46-0.86]), (OR: 0.42; 95% CI [0.29-0.60]), (OR:0.54; 95% CI [0.31, 0.94]), respectively. DAPT was also associated with higher short-term major bleeding risk (OR:2.66; 95% CI [1.46-3.86]). Furthermore, both DAPT and SAPT were associated with significantly higher long-term bleeding rates with (OR: 1.78; 95% CI, [1.15-2.41]) and (OR:2.32; 95% CI, [1.29-3.35]), respectively. However, VKAs were associated with lower long-term bleeding rates (OR: 0.61; 95% CI, [0.24-0.98]). No intervention showed a significant difference over DOACs in terms of long-term all-cause mortality, cardiovascular mortality, and stroke, except for DAPT which showed higher odds of long-term all-cause mortality (OR: 1.83; 95% CI, [1.29-2.37]). Conclusion: Despite the long-term higher rates of major bleeding, SAPT was effective in preventing both short and long-term all-cause mortality compared to DAPT, which has both short, long term major bleeding and higher long-term all-cause mortality. Further RCTs are still required to confirm SAPT superiority compared to other strategies.

Abstract 15692: Clinical Outcomes in TAVR Patients Receiving Oral Anticoagulation Stratified by Baseline Creatinine Clearance Levels: A Subanalysis of the ENVISAGE-TAVI AF Trial

Introduction: The ENVISAGE-TAVI AF (NCT02943785) trial compared edoxaban (EDO) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after successful transcatheter aortic valve replacement (TAVR). The effect of baseline creatinine clearance (CrCl) on efficacy and safety of EDO vs VKA in these patients is not well understood. Hypothesis: The efficacy and safety of EDO vs VKA in patients with AF undergoing TAVR will vary across the range of baseline CrCl. Methods: In this post-hoc analysis from the ENVISAGE-TAVI AF trial, we stratified patients by oral anticoagulation (OAC) strategy (EDO vs VKA) and CrCl (CrCl ≥90 mL/min, CrCl 60-89 mL/min, CrCl 45-59 mL/min, CrCl 30-44 mL/min, CrCl ≤29 mL/min). Results: Of 1426 patients included, 46.3% (n = 676) had CrCl from 60 to 89 mL/min. Patients with lower CrCl trended older in age than those with higher CrCl ( Table 1 ). The annualized event rates for all outcomes tended to increase with decreasing CrCl ( Table 2 ). Across the range of CrCl, patients receiving EDO vs VKA had higher rates of major bleeding and major gastrointestinal bleeding but lower rates of non-cardiovascular death. Major bleeding did not translate into increased all-cause death. Rates of intracranial hemorrhage were higher with EDO vs VKA in patients with CrCl ≥90 mL/min but lower in all other patients. For all-cause death, differences between EDO and VKA were numerical and did not reach statistical significance. Conclusions: In this ENVISAGE-TAVI AF subanalysis, decrements of CrCl appeared to correlate with rates of adverse outcome parameters more than OAC strategy. Due to low event rates in some outcomes, these results should be interpreted with caution.

Efficacy and safety of direct oral anticoagulants in splanchnic vein thrombosis: a pooled analysis of literature studies

BackgroundLimited evidence is available on management of splanchnic vein thrombosis (SVT). ObjectivesThis study aimed to evaluate safety and efficacy of direct oral anticoagulants (DOACs) for SVT treatment. MethodsStudies were systematically searched in the PubMed, Web of Science, and Scopus databases according to PRISMA guidelines. We assessed any recanalization, full recanalization, recurrence, mortality, and major bleeding as outcomes of interest. Results were reported as weighted mean prevalence (WMP) with 95% CI. Subgroup analyses and meta-regressions have been performed to address heterogeneity and adjust for potential confounders. ResultsWe included a total of 16 studies (17 datasets) on 648 patients with SVT treated with DOACs. We found any recanalization in 60.3% (95% CI: 41.8%-76.3%; I2 = 84.9%; P < .001) and full recanalization in 51.7% (95% CI: 36.0%-67.0%; I2 = 87.4%; P < .001). Recurrent venous thromboembolism occurred in 2.8% (95% CI: 1.4%-5.9%; I2 = 0%; P = .787) and death in 3.4% (95% CI: 1.6%-7.3%; I2 = 13.2%; P = .318) of patients. Major bleeding was reported by 5.8% (95% CI: 3.7%-8.9%; I2 = 29.2%; P = .125) of patients. Results were consistent when separately analyzing prospective studies, retrospective studies, studies on cirrhotic patients, and studies enrolling patients with portal vein thrombosis. Meta-regression analyses showed that an increasing age and cancer impacted the rate of recanalization. Cirrhosis was associated with a higher rate of major bleeding and mortality. ConclusionThe results of the present study, mostly based on observational studies, suggest good safety and efficacy profiles of DOACs in patients with SVT. Randomized studies are needed to corroborate our findings.

Evaluation of Lead-In Direct Oral Anticoagulant Prescribing Practices in Newly Diagnosed Venous Thromboembolism.

Various lead-in dosing strategies have been used in clinical practice for venous thromboembolism (VTE), and guidelines do not currently address if the full lead-in dosing duration is necessary after receiving parenteral anticoagulation. This study aims to identify whether full lead-in dosing duration surrounding parenteral anticoagulation affects thrombotic and bleeding outcomes. A single-center, retrospective cohort study was conducted of hospitalized patients diagnosed with VTE and treated with apixaban or rivaroxaban. Patients were grouped depending on duration of lead-in dosing, with the full lead-in dosing group considered as the appropriate duration of the direct oral anticoagulant. The primary outcome was the recurrence of VTE within the index admission to 6months. Secondary outcomes included major bleeding, clinically relevant minor bleeding, and mortality.Ninety-three patients were prescribed full lead-in dosing, while 99 patients received reduced lead-in dosing. The primary outcome of recurrent VTE was similar between the reduced lead-in group compared to the full lead-in group (3% vs 2%; P=1.0). Major bleeding within the index admission was significantly higher in the reduced lead-in group: 11 versus 2 (P=.02). There were no significant differences in other secondary outcomes. Full lead-in dosing compared to reduced lead-in dosing duration for VTE had similar rates of thrombotic and mortality events. The higher rate of major bleeding in the reduced lead-in dosing group likely reflects the prescribing practices in less stable patients. This study provides evidence to support reduced lead-in dosing duration in high-risk patients without compromising efficacy outcomes.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study

Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. Propensity score-matched cohort study. 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n= 5,720). Warfarin, rivaroxaban, or apixaban. Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. Few ischemic stroke events, potential residual confounding. In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

COVID-19–associated venous thromboembolism: risk of recurrence and major bleeding

BackgroundComplications under anticoagulant treatment in patients with COVID-19-associated venous thromboembolism (VTE) have not been consistently reported. ObjectivesThis study aimed to compare the 90-day rates of VTE recurrences and major bleeding in patients with COVID-19-associated VTE versus those with VTE without COVID-19. MethodsWe used the RIETE registry to compare the 3-month outcomes in patients with COVID-19-associated VTE versus those with VTE without COVID-19. ResultsThe study included 1,747 patients with COVID-19-associated VTE and 8,711 with VTE without COVID-19. Patients with COVID-19-associated VTE were more likely to be hospitalized at baseline and to present with pulmonary embolism. During the first 90 days, 123 patients (1.17%) developed VTE recurrences, and 266 (2.54%) experienced major bleeding. Patients with COVID-19-associated VTE had a similar rate of VTE recurrences (0.9% vs 1.2%) but a higher rate of major bleeding (4.6% vs 2.1%; P < .001) than those without COVID-19. Multivariable analysis adjusted for competing risks showed that patients with COVID-19-associated VTE had an increased risk of major bleeding (subhazard ratio, 1.395; 95% confidence interval, 1.037-1.877). The 30-day mortality after major bleeding was 26.3% in patients with COVID-19-associated VTE and 17.7% in those without COVID-19. ConclusionPatients with COVID-19-associated VTE had a 5-fold higher rate of major bleeding than VTE recurrences during the first 90 days of anticoagulation. In VTE patients without COVID-19, both rates were similar. These findings highlight the importance of carefully monitoring and optimizing anticoagulation in these patients.

Sex-Related Differences in Patient Characteristics, Hemodynamics, and Outcomes of Cardiogenic Shock: INOVA-SHOCK Registry.

Little is known about sex-related differences in outcomes of patients with cardiogenic shock (CS) treated within a standardized team-based approach (STBA). We evaluated 520 consecutive patients (151 women and 369 men) with CS due to acute myocardial infarction (AMI) and heart failure (HF) in a single-center registry (January 2017-December 2019) and examined outcomes according to sex and CS phenotype. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiac events, 30-day mortality, major bleeding, vascular complications, and stroke. Women with AMI-CS had higher baseline acuity (CardShock score: female [F]: 5.5 vs male [M]: 4.0; P = .04). Women with HF-CS more often presented with cardiac arrest (F: 12.4% vs M: 2.4%; P< .01) and had higher rates of vasopressor use (F: 70.8% vs M: 58.0%; P = .04) and mechanical circulatory support (F: 46.1% vs M: 32.5%; P = .04). There were no sex-related differences in in-hospital mortality for AMI-CS (F: 45.2% vs M: 36.9%; P = .28) and HF-CS (F: 28.1% vs M: 24.5%; P = .56). Women with HF-CS experienced higher rates of major bleeding (F: 25.8% vs M: 13.7%; P = .02) and vascular complications (F: 15.7% vs M: 6.1%; P = .01). However, female sex was not an independent predictor of these complications. No sex differences in survival were noted at 1 year. Within an STBA, although women with AMI-CS and HF-CS presented with higher acuity, they experienced similar in-hospital mortality, major adverse cardiac events, 30-day mortality, stroke, and 30-day readmissions as men. Further research is needed to better understand the extent to which historical differences in CS outcomes can be mitigated by an STBA.

Efficacy and safety of direct oral anticoagulants in older adults with atrial fibrillation: a prospective single-centre cohort study.

Direct oral anticoagulants (DOACs) are underused in the elderly, regardless the evidence in their favour in this population. We prospectively enrolled anticoagulant-naïve patients aged ≥ 75years who started treatment with DOACs for atrial fibrillation (AF) and stratified them in older adults (aged 75-84years) and extremely older adults (≥ 85years). Thrombotic and hemorrhagic events were evaluated for 12months follow-up. We enrolled 518 consecutive patients. They were mostly aged 75-84years (299 patients; 57.7%) vs. ≥ 85years (219 patients; 42.3%). Extremely older adults showed higher incidence of all the endpoints (systemic cardioembolism [HR 3.25 (95% CI 1.71-6.18)], major bleeding [HR 2.75 (95% CI 1.77-4.27)], and clinically relevant non-major bleeding [HR 2.13 (95% CI 1.17-3.92)]) vs. older adults during the first year after starting anticoagulation. In patients aged ≥ 85years, no difference in the aforementioned endpoints was found between those receiving on-label vs. off-label DOACs. In the extremely older adults, chronic kidney disease, polypharmacy, use of antipsychotics, and DOAC discontinuation correlated with higher rates of thrombotic events, whereas a history of bleeding, Charlson Index ≥ 6, use of reduced DOAC dose, absence of a caregiver, use of non-steroidal anti-inflammatory drugs (NSAIDs), and HAS-BLED score ≥ 3 were associated with major bleedings. Naïve patients aged ≥ 85 who started a DOAC for AF are at higher risk of thrombotic and bleeding events compared to those aged 75-84years in the first year of therapy. History of bleeding, HAS-BLED score ≥ 3 and use of NSAIDs are associated with higher rates of major bleeding.

Clinical Significance and Outcome in Patients with Asymptomatic Versus Symptomatic Subsegmental Pulmonary Embolism

The clinical significance and optimal therapy of patients with subsegmental pulmonary embolism (SSPE) remain controversial. We used the data in the RIETE Registry to compare the baseline characteristics, treatment, and outcomes during anticoagulation and after its discontinuation in patients with asymptomatic vs. symptomatic SSPE. From January 2009 to September 2022, there were 2135 patients with a first episode of SSPE, of whom 160 (7.5%) were asymptomatic. Most patients in both subgroups received anticoagulant therapy (97% vs. 99.4%, respectively). During anticoagulation, 14 patients developed symptomatic pulmonary embolism (PE) recurrences, 28 lower-limb deep vein thrombosis (DVT), 54 bled, and 242 died. The patients with asymptomatic SSPE had similar rates of symptomatic PE recurrences (hazard ratio (HR): 2.46; 95% CI: 0.37-9.74), DVT (HR: 0.53; 95% CI: 0.03-2.80), or major bleeding (HR: 0.85; 95% CI: 0.21-2.42) to those with symptomatic SSPE, but had a higher mortality rate (HR: 1.59; 95% CI: 1.25-2.94). The rate of major bleeding outweighed the rate of PE recurrences (54 major bleeds vs. 14 PE recurrences), and the rate of fatal bleeds outweighed the rate of fatal PE recurrences (12 vs. 6 deaths). After discontinuing anticoagulation, the patients with asymptomatic SSPE had a similar rate of PE recurrences (HR: 1.27; 95% CI: 0.20-4.55) and a non-significantly higher mortality rate (HR: 2.06; 95% CI: 0.92-4.10). The patients with asymptomatic SSPE had similar rates of PE recurrences to those with symptomatic SSPE, during and after discontinuing anticoagulation. The unexpectedly higher rate of major bleeding than recurrences highlights the need for randomized trials to find the best management.

Novel Oral Anticoagulants in Patients With Atrial Fibrillation and Moderate to Severe Mitral Stenosis: A Systematic Review.

The use of novel oral anticoagulants (NOAC) in patients with moderate to severe mitral stenosis (MS) and atrial fibrillation (AF) is not recommended.We aimed to evaluate the efficacy and safety of NOAC usage compared to vitamin K antagonist (VKA) in patients with moderate to severe MS and AF.We conducted a systematic review to identify articles that compared warfarin to NOAC in patients with moderate to severe MS and AF. Only four studies (two observational studies and two trials) met our search criteria and reported a total of 7529 patients with MS and AF with MS and AF, 4138 of them treated with NOAC. In both observational studies, the severity of MS was not determined, and there was heterogeneity in MS etiology. Nevertheless, both studies showed a positive signal toward the efficacy and safety of NOAC compared to VKA in this population. A randomized pilot trial (n=40) was done on patients with moderate to severe MS, and it showed further acceptable efficacy and safety for rivaroxaban use. However, a larger randomized controlled trial (n=4531) disclosed that VKA (warfarin) led to a significantly lower rate of a composite of cardiovascular events or mortality than rivaroxaban, without a higher rate of major bleeding but not fatal bleeding. Our systematic review provides exploratory information on NOAC safety and effectiveness in patients with MS; it also discourages using NOACs for patients with moderate to severe MS and supports the current treatment guidelines. However, more dedicated clinical trials evaluating the use of NOACs in moderate to severe MS are underway. They will categorically establish the safety profile and clinical effectiveness of NOAC in this high-risk population.

Abstract 14027: Use of Anticoagulation or Antiplatelets in Patients With Cardiac Arrest Without ST-Segment-Elevation or Percutaneous Coronary Intervention

Introduction: There are limited data on the use of anticoagulation (AC) and anti-platelet (AP) agents in addition to aspirin compared to standard of care (aspirin alone) in cardiac arrest (CA) patients without ST-segment-elevation and not undergoing a percutaneous coronary intervention. Hypothesis: We hypothesized that use of AC/AP agents in CA is associated with lower mortality compared to aspirin alone. Methods: A comprehensive literature search was performed from inception to 09/30/2021 of the PubMed/EMBASE databases. Studies of adult patients comparing AC/AP to aspirin alone were evaluated for short-term mortality (30-days survival/survival to hospital discharge), significant bleeding, and return of spontaneous circulation (ROSC). Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results: Of a total 5337 studies, five studies (2 randomized trials and 3 observational studies) with 3,696 subjects (1,196 intervention and 2,500 placebo arm) were included. Overall, there was no evidence of publication bias using either funnel plot or eggers test. For RCT studies, mean age was 60.8 years (males 79.2%), while for observational study mean age was between 58 to 62.3 years (males 58-62.3%). Use of AP/AC was associated with higher rates of major bleeding (odds ratio [OR] = 2.43 [95% confidence interval {CI} 1.35- 4.37]; p=0.003; I2=7%; 4 studies) compared with aspirin alone. There was no significant difference in ROSC (OR= 1.24 [95% CI 0.68-2.26]; p=0.49; I2=57%; 3 studies) and short-term mortality [OR= 1.24 [95% CI 0.87-1.76]; p=0.24; I2=69%; 3 studies) between intervention and placebo arm. Conclusions: In this meta-analysis, use of concomitant AC/AP therapy with aspirin in CA without ST-segment-elevation or percutaneous coronary intervention was associated with higher rates of bleeding without improvement in short-term mortality or ROSC.

Abstract 13657: Evaluating Outcomes of Half-Dose Tissue Plasminogen Activator on Patients With Intermediate-Risk Pulmonary Embolism: A Single Center Study

Introduction: In the absence of hypotension, pulmonary embolism (PE) causing right ventricular dysfunction or strain whether confirmed by imaging or cardiac biomarkers is deemed to be an intermediate-risk category. Urgent treatment of intermediate-risk PE can prevent progression to hemodynamic instability and death. Management options include thrombolysis, thrombectomy, or systemic anticoagulation. We aim to evaluate the short-term outcomes of a half-dose tissue plasminogen activator(tPA) for the management of intermediate-risk PE. Methods: We retrospectively identified adult patients diagnosed with intermediate-risk PE between the years 2000 and 2021. Demographic data, lab values, imaging, treatment choice, and outcomes were all obtained through chart review. Patients on standard systemic anticoagulation without thrombolysis or thrombectomy served as controls. Data analysis was done through SAS® Software (version 9.4; Cary, NC) to compare those that received half-dose tPA with controls and statistical significance was set at a p-value of 0.05. Results: We included 57 patients in our final analysis with 19 receiving tPA. Patient characteristics and comorbidities were comparable between both groups. There was a significant difference between PE location, presence of acute deep vein thrombosis, and peak troponin level between both groups (Table 1). The thrombolytic cohort was more likely to have a 60/60 sign and a thrombus in transit on echocardiography than controls. The thrombolytic group was more likely to have major bleeding (17% vs 7.9%, p= 0.4) and in-hospital mortality (5.3% vs 0%, p=0.3), however, this was not statistically significant. Conclusion Patients who received half-dose tPA had non-significant higher rates of major bleeding and in-hospital mortality. Larger scale, randomized control trials are needed to establish the benefit and safety of thrombolytics in patients with intermediate-risk PE.

Abstract 11427: Clot Strength and Platelet Reactivity for Prediction of Major Cardiovascular Events After Percutaneous Coronary Intervention

Introduction: Platelet-fibrin clot strength (PFCS) is associated with the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Hypothesis: The interaction between PFCS and platelet reactivity, and their prognostic implication remain uncertain. Methods: We enrolled CAD patients undergoing percutaneous coronary intervention (PCI) with available PFCS (measured by thromboelastography) and platelet reactivity (measured by VerifyNow). PFCS High was defined as maximal amplitude (MA)≥68, and high platelet reactivity (HPR) was categorized as P2Y12 reaction unit (PRU) &gt;208. Patients were stratified into 4 groups according to the levels of MA and PRU: (1) normal platelet reactivity (NPR)-PFCS Low (31.9%); (2) HPR-PFCS Low (28.9%); (3) NPR-PFCS High (18.1%); and (4) HPR-PFCS High (21.1%). The primary endpoint was MACE (a composite of all-cause death, myocardial infarction, or stroke) and the risk of major bleeding was also evaluated. Results: At 4-year follow-up, prognostic implication of HPR and PFCS High showed the synergistic effect, and risks of MACE were significantly different across the groups (log-rank test, P &lt; 0.001) (Figure 1). Compared with the NPR-PFCS Low group, the HPR-PFCS High group only showed a significantly higher risk of MACE (adjusted hazard ratio [HR adj ]: 1.87; 95% confidence interval [CI]: 1.22-2.87; p=0.004). In addition, the HPR-PFCS High group had a greater rate of MACE compared with the HPR-PFCS Low group (HR adj : 1.47; 95% CI: 1.04-2.09; p=0.03). Similar results were revealed in the risk of all-cause death. Compared with HPR-PFCS Low , NPR-PFCS Low was associated with a higher major bleeding rate (HR adj : 3.03; 95% CI: 1.27-7.14; p=0.01). Conclusions: In PCI-treated patients, PFCS and HPR phenotypes show important relationships in the occurrence of adverse clinical events. Therefore, a combined assessment of clot strength and platelet reactivity may enhance post-PCI risk stratification.

СРАВНЕНИЕ ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ИНГИБИТОРОВ P2Y12 РЕЦЕПТОРОВ У ПАЦИЕНТОВ С ИНВАЗИВНОЙ СТРАТЕГИЕЙ ВЕДЕНИЯ ОСТРОГО КОРОНАРНОГО СИНДРОМА

Dual antiplatelet therapy (DAPT) using of acetylsalicylic acid and antagonists of platelet’s P2Y12 receptors is included in standards for treatment of patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Clopidogrel, prasugrel, and ticagrelor are the P2Y12 receptor inhibitors used as a component of DAPT. The aim of this review is to determine the most effective and the safest P2Y12 receptor inhibitor for treating patients with an invasive treatment strategy of ACS. The TRITON study compared clopidogrel and pragugrel efficacy and safety had demonstrated a significantly higher efficiency in reducing the risk of reaching the primary endpoint (including cardiovascular death, myocardial infarction and stroke) for prasugrel, but at the same time, the prasugrel group was reliably recorded higher rate of major bleeding. Comparison of the efficacy and safety of clopidogrel and ticagrelor was carried out in the PLATO study, where ticagrelor was shown to be more effective in reducing cardiovascular deaths and myocardial infarction, while the safety of the drugs was comparable. A subsequent ISAR-REACT 5 study proved higher efficacy of prasugrel compared to ticagrelor in reducing the risk of reaching a primary endpoint with comparable safety to the major bleeding risk. Baseline data represents that the most effective drug among P2Y12 receptor inhibitors as a component of DAPT for patients with an invasive treatment strategy is prasugrel, and the safest is clopidogrel, which can be considered in elderly patients.

Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p=.50), with cancer (4.16 vs. 4.89, p=.370), and without cancer patients (0.89 vs. 2.80, p=.25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p=.03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p=.006) even after adjustment (p=.05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p=.03), but not after adjustment (p=.974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p=.007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.

СРАВНЕНИЕ ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ИНГИБИТОРОВ P2Y12 РЕЦЕПТОРОВ У ПАЦИЕНТОВ С ИНВАЗИВНОЙ СТРАТЕГИЕЙ ВЕДЕНИЯ ОСТРОГО КОРОНАРНОГО СИНДРОМА

Dual antiplatelet therapy (DAPT) using of acetylsalicylic acid and antagonists of platelet’s P2Y12 receptors is included in standards for treatment of patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Clopidogrel, prasugrel, and ticagrelor are the P2Y12 receptor inhibitors used as a component of DAPT. The aim of this review is to determine the most effective and the safest P2Y12 receptor inhibitor for treating patients with an invasive treatment strategy of ACS.&#x0D; The TRITON study compared clopidogrel and pragugrel efficacy and safety had demonstrated a significantly higher efficiency in reducing the risk of reaching the primary endpoint (including cardiovascular death, myocardial infarction and stroke) for prasugrel, but at the same time, the prasugrel group was reliably recorded higher rate of major bleeding.&#x0D; Comparison of the efficacy and safety of clopidogrel and ticagrelor was carried out in the PLATO study, where ticagrelor was shown to be more effective in reducing cardiovascular deaths and myocardial infarction, while the safety of the drugs was comparable.&#x0D; A subsequent ISAR-REACT 5 study proved higher efficacy of prasugrel compared to ticagrelor in reducing the risk of reaching a primary endpoint with comparable safety to the major bleeding risk.&#x0D; Baseline data represents that the most effective drug among P2Y12 receptor inhibitors as a component of DAPT for patients with an invasive treatment strategy is prasugrel, and the safest is clopidogrel, which can be considered in elderly patients.

Inotropes, vasopressors, and mechanical circulatory support for treatment of cardiogenic shock complicating myocardial infarction: a systematic review and network meta-analysis.

To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction. We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality. We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis. The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding. Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020.

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

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