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Background: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use., Methods: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days., Results: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; P interaction  = 0.07) or its individual components between bivalirudin and heparin groups., Conclusions: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI., Trial Registration: ClinicalTrials.gov NCT03822975., (© 2024. The Author(s).)

Background: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years., Methods: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here., Results: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups., Conclusions: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02311231., Competing Interests: Declaration of competing interest Elmir Omerovic reports grants from Astra Zeneca, personal fees from Astra Zeneca, MSD, Bayer, Janssen outside the submitted work. Stefan James reports grants from Astra Zeneca, grants from The Medicines Company, grants from Swedish Heart and Lung Foundation, and grants from Swedish Research Council during the conduct of the study; personal fees from Bayer and grants from Jansen outside the submitted work. Truls Råmunddal reports personal fees from Boston Scientific and personal fees from Abbot outside the submitted work. Ole Fröbert reports personal fees from GE Medical and from Astra Zeneca outside the submitted work. Pontus Lindroos reports personal fees from Astra Zeneca outside the submitted work. Anders Ulvenstam reports personal fees from Boston Scientific outside the submitted work. Matthias Götberg reports grants and personal fees from Volcano Corporation, personal fees from Boston Scientific, and personal fees from Medtronic Corporation outside the submitted work. Oskar Angerås Dr. reports personal fees from Astra Zeneca outside the submitted work. Olie Östlund reports grants from AstraZeneca, grants from The Medicines Company. Cleas Held reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from BristolMyers Squibb, and grants from Merck outside the submitted work. Sasha Koul reports personal fees from Pfizer, personal fees from BMS, and personal fees from Astra Zeneca outside the submitted work. David Erlinge reports personal fees from Astrazeneca and The Medicines Company outside the submitted work. All others co-authors have nothing to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI., Methods: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs)., Results: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003)., Conclusion: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin., Case Presentation: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia., Conclusion: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions., (© 2024. The Author(s).)

Introduction: Unfractionated heparin (UFH) has traditionally been the agent of choice in patients on extracorporeal membrane oxygenation (ECMO). However, direct thrombin inhibitors (DTI) have recently garnered more attention in ECMO because of their advantages over UFH. Given the heterogeneous results of multiple recent published studies, we performed a meta-analysis to describe pooled outcomes between bivalirudin and UFH anticoagulation in patients on ECMO. Methods: Relevant studies were identified from MEDLINE and Google Scholar database searches through April 23, 2022. The primary efficacy outcome was thromboembolism (TE), and secondary efficacy outcomes included all-cause mortality and circuit thrombosis. The primary safety outcome was major bleeding. Results: A total of 6 studies were included in the meta-analysis. Bivalirudin use was associated with significantly lower risk of TE (OR 0.61; 95% CI 0.38-.99; P = .05; I 2 = 0%) and circuit thrombosis (OR 0.51; 95% CI .32-.80; P = .004; I 2 = 0%) compared with UFH. There was no significant difference in all-cause mortality risk (OR 0.75; 95% CI .52-1.09; P = .13; I 2 = 30%) between the bivalirudin and UFH groups. No significant difference in the risk of major bleeding between 2 groups was found (OR 0.67; 95% CI 0.25-1.81; P = .43; I 2 = 80%). Conclusion: These data support that bivalirudin is a reasonable alternative to UFH in patients on ECMO. Randomized controlled trials are needed to confirm bivalirudin's efficacy and safety results compared with UFH., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Bivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI., Methods: We have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI)., Results: Ten RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %)., Conclusion: Our meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bivalirudin as an anticoagulant reduces bleeding after percutaneous coronary intervention (PCI), while its impact in elderly Chinese patients treated with PCI needs more evidence. This study aimed to compare the clinical outcomes between bivalirudin and heparin in elderly Chinese patients treated with PCI. This cohort study retrieved data of 1,286 elderly patients treated with PCI who used bivalirudin (bivalirudin group, N = 493) or heparin (heparin group, N = 793) as anticoagulants. Net adverse clinical events (NACEs) (primary endpoint), major adverse cardiac and cerebral events (MACCEs), bleeding, and major bleeding within 30 days after PCI treatment were recorded for analysis. Our study illustrated that NACEs (12.4% vs. 17.4%, P = 0.015), bleeding (6.7% vs. 12.1%, P = 0.002), and major bleeding (2.2% vs. 6.6%, P < 0.001) were fewer in bivalirudin group compared to heparin group. No difference was found in MACCEs (7.5% vs. 9.6%,P = 0.200), and incidences of all-cause mortality (P = 0.257), cardiac mortality (P = 0.504), recurrent myocardial infarction (P = 0.423), ischemia-driven revascularization (P = 0.509), and stroke (P = 0.467), between bivalirudin group and heparin group. According to univariate logistic regression analyses, bivalirudin (vs. heparin) correlated with fewer NACEs (P = 0.016), bleeding (P = 0.002), and major bleeding (P = 0.001) in elderly patients treated with PCI, but not MACCEs (P = 0.202). After adjustment, bivalirudin (vs. heparin) was an independent factor for fewer NACEs [odds ratio (OR): 0.619, P = 0.009], bleeding (OR: 0.499, P = 0.003), and major bleeding (OR: 0.342, P = 0.003) in these patients. In summary, bivalirudin achieves fewer NACEs, bleeding, and major bleeding, but not MACCEs, versus heparin in elderly patients treated with PCI, which is verified in the multivariate model.

Background: Bivalirudin is associated with fewer major bleeding events than heparin in patients undergoing percutaneous coronary intervention (PCI), but confounding effects of concomitant glycoprotein IIb/IIIa inhibitors, routine femoral artery access, and less potent effects of clopidogrel limits meaningful comparisons. The present study is a systematic review and meta-analysis to compare bivalirudin to heparin in contemporary practice., Methods: The Cochrane Library, PubMed, EMBASE, and Ovid MEDLINE databases were searched for relevant studies, including comparisons between bivalirudin and heparin in the current medical era from inception to December 23, 2021. Studies reporting incidences of major adverse cardiac events (MACE) and net adverse clinical events (NACE) in patients undergoing PCI and meeting the inclusion criteria were retained. Data extraction was performed by three independent reviewers., Results: The meta-analysis included 8 studies. Compared to heparin, bivalirudin during PCI was associated with a lower NACE risk, lower all-cause death, and similar MACE risk, with a pooled risk ratio of 0.82 (95% confidence interval [CI] 0.69-0.97, p = 0.02), 0.83 (95% CI 0.74-0.94, p = 0.002), and 0.93 (95% CI 0.78-1.10, p = 0.38), respectively. Moreover, the reduction in NACE was mainly attributed to reduced bleeding (22% reduction in the risk of major bleeding, 95% CI 0.63-0.97, p = 0.03)., Conclusions: These findings suggest that bivalirudin use during PCI reduced the risk of NACE and all-cause death but did not reduce the risk of MACE compared with heparin use in PCI. More studies specifically designed for anticoagulation strategies and a personalized anticoagulation regimen to comprehensively balance bleeding and ischemia risks are required.

Background: Publication of the BRIGHT-4 trial results has restimulated discussion about the optimal periprocedural antithrombotic strategy for patients undergoing percutaneous coronary intervention (PCI) with acute coronary syndromes (ACS). It is possible that variation in the infusion duration, may contribute to observed differences in safety-efficacy profiles of bivalirudin in this clinical setting., Methods: Up to December 2022, randomized controlled trials (RCTs) comparing bivalirudin (either administered peri-procedurally or accompanied by postprocedural infusion) and heparin, both with or without GPI, were searched and entered in a frequentist network meta-analysis. Co-primary endpoints were trial-defined major adverse composite events (MACE) and major bleeding. Incident rate ratios (IRR) and 95 % confidence intervals (CI) were estimated., Results: 10 RCTs (N = 57,137 patients/month) were included. As compared to heparin, prolonged bivalirudin infusion resulted in lower rates of major bleeding (IRR 0.58, 95 % CI 0.36-0.91), but there was no differences in MACE rates between these strategies. With regard to NACE, prolonged bivalirudin infusion yielded lower risk (IRR 0.86, 95 % CI 0.77-0.96), whereas both bivalirudin and heparin increased risk when coupled with GPI (IRR 1.24, 95 % CI 1.01-1.51 and IRR 1.24, 95 % CI 1.06-1.44, respectively). Both these combination strategies also increased minor bleeding rates (IRR 1.49, 95 % CI 1.16-1.93 and IRR 1.58, 95 % CI 1.29-1.95, respectively, for bivalirudin and heparin). Results were consistent across several sensitivity analyses., Conclusion: In patients with ACS undergoing PCI, procedural bivalirudin administration followed by prolonged infusion results in lower major bleeding rates, but there does not appear to be a difference in observed MACE., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population., Methods: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4., Results: Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61-0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74-0.98), any bleeding (OR 0.61, CI 0.45-0.83), major bleeding (OR 0.54, CI 0.39-0.75), all-cause mortality (OR 0.79, CI 0.67-0.92) and cardiac mortality (OR 0.78, CI 0.65-0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52-1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62-2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69-6.09) significantly at 30 days., Conclusion: Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.

Background: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI., Methods: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding., Results: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P =0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P <0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up., Conclusions: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites., Competing Interests: Disclosures Dr Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to 2 brand models of inferior vena cava filters and is supported by the Scott Schoen and Nancy Adams IGNITE award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and a career development award from the American Heart Association and VIVA Physicians (No. 938814). Dr Erlinge has received honoraria for advisory boards from AstraZeneca, Bayer, Chiesi, and Sanofi, and speaker honoraria from Bayer, AZ, Novartis, and Chiesi. Dr Valgimigli reports personal grants and personal fees from Terumo, and personal fees from Astra Zeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CorFlow, Idorsia Pharmaceuticals, Universität Basel Dept Klinische Forschung, Bristol Myers Squib SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Steg has received research grants from Amarin, AstraZeneca, Bayer, Sanofi, and Servier and honoraria for clinical trials (steering committee, clinical events committee, Data Safety and Monitoring Board) from Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, Servier, and The Medicines Company, and for consulting or speaking from Amarin, Amgen, Bristol Myers Squibb, Novo-Nordisk, and Regeneron. Dr Steg is a senior associate editor at Circulation. Dr Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; reports personal fees from Cine-Med Research, and WebMD; reports equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); is in the scientific advisory board for American Medical Association, American College of Cardiology (Board of Trustee member), Society of Cardiovascular Angiography and Intervention (Women in Innovations committee member), is a JAMA associate editor; and is among the faculty at Cardiovascular Research Foundation (no fee). Dr James’s employer has received research grants from Novartis, Amgen, Jansen, Bayer, AstraZeneca, and Infraredex. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at IQVIA. Institutional disclosure: Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. The other authors report no conflicts.

Background: Patients with diabetes and coronary artery disease have a higher risk of bleeding and thrombotic events. However, data on the safety and efficacy of bivalirudin in these patients undergoing elective percutaneous coronary intervention (PCI) are lacking., Methods: 1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10,250 patients anticoagulated with unfractionated heparin (UFH) (with or without glycoprotein IIb/IIIa inhibitors [GPI]) were performed propensity-score matching method. The thrombotic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The bleeding endpoint was according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding., Results: Finally, 376 (bivalirudin group) and 878 (UFH group) patients with type 2 diabetes (T2D) were enrolled. After one-year follow-up, there were 130 (10.4%) MACCE and 27 (2.2%) bleeding events occurred. Multivariate COX regression analysis showed no significant difference for MACCE between bivalirudin group and UFH group (P > 0.05). Further analysis showed that there was a reduction in the risk of myocardial infarction (MI) between two groups (Hazard ratio [HR] = 0.199, 95% confidence interval [CI]: 0.047-0.845, P = 0.029), but not in the risk of death, revascularization, stent thrombosis or stroke (all P > 0.05). As for BARC 2, 3 or 5 bleeding, no significant difference was found between two groups (P > 0.05)., Conclusions: Although diabetes is considered a high-risk factor for poor prognosis, compared with UFH (with or without GPI), bivalirudin did not increase the risk of MACCE and even decreased the risk of MI in patients with T2D undergoing elective PCI, while the risk of bleeding was similar between two groups., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xueyan Zhao reports article publishing charges was provided by Chinese Academy of Medical Sciences & Peking Union Medical College Fuwai Hospital., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Bivalirudin has been suggested as an alternative to heparin for anticoagulation in patients receiving extracorporeal membrane oxygenation (ECMO). Nevertheless, there is limited evidence about the benefit of bivalirudin in ECMO patients compared with heparin. Hence, we conducted a meta-analysis to assess the effect of bivalirudin versus heparin on clinical outcomes in patients receiving ECMO., Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception up to 1 April 2022 for cohort studies and randomized controlled trials comparing bivalirudin versus heparin in patients who received ECMO. The primary outcome was short-term death. Secondary outcomes included thrombotic events and bleeding events., Results: We selected 12 retrospective cohort studies with 1232 ECMO patients focusing on bivalirudin anticoagulation (n = 497) versus heparin anticoagulation (n = 735). Two hundred and one of 497 patients (40.4%) in the bivalirudin group versus 350 of 735 patients (47.6%) in the heparin group did not survive to hospital discharge. Compared with the heparin group, bivalirudin anticoagulation did not significantly decrease in-hospital mortality in patients receiving ECMO (RR, 0.95; 95% CI, 0.79-1.13; p = 0.546). Fifty-seven of 374 patients (15.2%) in the bivalirudin versus 99 of 381 patients (26.0%) in the heparin group suffered from thrombotic events. Compared with the heparin group, bivalirudin anticoagulation did not significantly decrease the rate of thrombotic events for patients receiving ECMO (RR, 0.78; 95% CI, 0.45-1.35; p = 0.378). However, bivalirudin anticoagulation significantly decreased the incidence of bleeding events compared to the heparin group (RR, 0.48; 95% CI, 0.25-0.95; p = 0.035)., Conclusions: Compared with heparin anticoagulation, bivalirudin did not decrease the rates of short-term mortality and thrombotic events, but reduced the incidence of bleeding events in patients receiving ECMO.

Introduction: Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI)., Areas Covered: Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients. Furthermore, a significant body of evidence has demonstrated that the risk of acute ST can be mitigated by a full-dose infusion regimen following PCI, without compromising the favorable safety profile compared to UFH., Expert Opinion: In light of the increased understanding of the prognostic relevance of bleeding events and the excellent safety profile of bivalirudin, recent trial evidence may allow for this anticoagulant agent to reemerge and have a more prominent role in the management of ACS patients undergoing PCI.

Objective: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR)., Background: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact., Methods: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure., Results: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding)., Conclusion: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD., (© 2023 Wiley Periodicals LLC.)

Background: No evidence exists on the impact of bivalirudin in patients with the acute coronary syndrome undergoing rotational atherectomy. This study aimed to evaluate the impact of bivalirudin on patients with acute coronary syndrome undergoing rotational atherectomy., Methods: This was a retrospective cohort study conducted in our hospital between January 2017 and December 2019. The study included patients with acute coronary syndrome undergoing rotational atherectomy. Furthermore, 2 cohorts were included in this study (bivalirudin cohort and control cohort unfractionated heparin). The primary end-point was in-hospital net adverse clinical events. The secondary endpoint was all-cause mortality at 23 months., Results: The study included 157 patients with 33 (21.0%) in the bivalirudin cohort and 124 (79.0%) in the control cohort. Net adverse clinical events during hospitalization in the bivalirudin cohort were higher than that in the control cohort [9 (27.3%) vs. 14 (11.3%), P = .021]. However, there was no significant difference in all-cause mortality at 23 months between the 2 cohorts [25 (20.2%) vs. 10 (30.3%), P =.214]. After adjusting for potential confounders, the usage of bivalirudin was not associated with net adverse clinical event (odds ratio = 0.90; 95% CI: 0.18-4.45; P =.890), and the hazard ratio for all-cause mortality at 23 months was 1.01 (95% CI: 0.33-3.15; P =.983)., Conclusion: Bivalirudin appears to exhibit a similar impact as unfractionated heparin on patients with acute coronary syndrome undergoing rotational atherectomy in real-life setting.

The effect and safety of bivalirudin compared with heparin in patients undergoing extracorporeal membrane oxygenation (ECMO) remains unclear. Therefore, we conducted a systematic review and meta-analysis to compare the effectiveness and safety of heparin and bivalirudin in patients who underwent ECMO. We searched Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE. Inclusion criteria included patients (1) undergoing ECMO and (2) receiving bivalirudin or heparin. We excluded studies where the majority of patients switched heparin to bivalirudin or vice versa during the clinical course. The primary outcome was short-term mortality. We presented the results of all analyses with the use of random-effects models. Eleven studies reported short-term mortality. The use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin (odds ratio: 0.71, 95% confidence interval, 0.55-0.92; p = 0.01, I2 = 7%). In this meta-analysis of observational studies, the use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin. Further prospective studies are warranted to clarify this finding., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25-3.37, p = 0.005, I2 = 0%) and die (OR 1.62, 95% CI 1.19-2.21, p = 0.002, I2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55-6.09, p = 0.33, I2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Background: Impella 5.5 (Abiomed; Danvers, MA) (IMP5) is a commonly used, surgically implanted, tMCS device that requires systemic anticoagulation and purge solution to avoid pump failure. To avoid heparin-induced thrombocytopenia (HIT) from unfractionated heparin (UFH) use, our program has explored the utility of bivalirudin (BIV) for systemic anticoagulation and sodium bicarbonate-dextrose purge solution (SBPS) in IMP5.5., Methods: This single center, retrospective study included 34 patients supported on IMP5.5 with BIV based AC and SBPS between December 1st 2020 to December 1st 2021.The efficacy and safety end points were incidence of development of HIT, Tissue Plasminogen Activator (tPA) use for suspected pump thrombosis, stroke, and device failure as well as clinically significant bleeding., Results: The median duration of IMP5.5 support was 9.8 days (IQR: 6-15). Most patients were bridged to HTX (58%) followed by recovery (27%) and LVAD implantation (15%). Patients were therapeutic on bivalirudin for 64% of their IMP5.5 support. One patient (2.9%) suffered from ischemic stroke and 26.5% (9) patients developed clinically significant bleeding. tPA was administered to 7(21%) patients. One patient in the entire cohort developed HIT., Conclusions: Our experience supports the use of systemic BIV and SBPS as a method to avoid heparin exposure in a patient population predisposed to the development of HIT., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

This study describes the use of bivalirudin in children on extracorporeal membrane oxygenation (ECMO). Pediatric patients receiving bivalirudin were compared to patients receiving heparin as the anticoagulant on ECMO. Data was collected for children under 18 years of age supported by ECMO from January 2016 to December 2019. Data collected included demographics, diagnosis, ECMO indication, type, and duration, indication for bivalirudin use, dose range, activated partial thromboplastin time (aPTT) levels, minor and major bleeding, hemolysis, and mortality. Forty pediatric patients received ECMO; eight received bivalirudin primarily for anticoagulation. The median age was 4 months (IQR 0.5, 92) in the heparin cohort, 0.6 months (IQR 0.0, 80.0) in the primary bivalirudin cohort. The indication for ECMO was respiratory in 5 patients (18%) in the heparin group versus 6 (75%) in the primary bivalirudin group, cardiac in 18 (67%) in heparin versus 1 (12.5%) in primary bivalirudin, and extracorporeal-cardiopulmonary resuscitation (E-CPR) in 4 (15%) in heparin versus 1 (12.5%) in primary bivalirudin. Bivalirudin was the initial anticoagulant for eight patients (66.6%) while three (25%) were switched due to concern for heparin-induced thrombocytopenia (HIT) and one (8%) for heparin resistance. The median time to achieve therapeutic aPTT was 14.5 hours compared to 12 hours in the heparin group. Sixty-five percent of aPTT values in the bivalirudin and 44% of values in the heparin group were in the therapeutic range in the first 7 days. Patients with primary bivalirudin use had significantly lower dose requirement at 12 (p = 0.003), 36 (p = 0.007), and 48 (p = 0.0002) hours compared to patients with secondary use of bivalirudin. One patient (12.5%) had major bleeding, and two patients (25%) required circuit change in the primary bivalirudin cohort. Bivalirudin may provide stable and successful anticoagulation in children. Further large, multicenter studies are needed to confirm these findings.

Introduction: Optimal anticoagulants for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are unclear. This retrospective observational study is aimed at evaluating efficacy and safety of bivalirudin versus unfractionated heparin (UFH) monotherapy in patients with DM undergoing PCI., Methods: A total of 3890 diabetic patients receiving PCI in the General Hospital of Northern Theater Command were divided into the bivalirudin group ( n = 869) and the UFH group ( n = 3021) according to different anticoagulant therapy regimens. Indication for PCI was in accordance with current guidelines including national cardiovascular data registry. The primary endpoint was 30-day net adverse clinical events (NACEs). The secondary endpoints included 30-day major adverse cardiac and cerebral events (MACCEs), bleeding events defined according to the Bleeding Academic Research Consortium (BARC) definition, and stent thrombosis (ST). Patients were matched by propensity score at a ratio of 1 : 1., Results: After propensity score matching, the bivalirudin group was associated with a lower incidence of NACEs (3.0% vs. 6.0%, P = 0.003) than the UFH group. The incidence of MACCE (1.7% vs. 3.3%, P = 0.033) was significantly lower in the bivalirudin group, mainly due to a lower mortality rate (0.6% vs. 2.0%, P = 0.010). In addition, patients in the bivalirudin group had less bleeding (1.4% vs. 3.0%, P = 0.022) than those in the UFH group, although BARC 2, 3, and 5 bleeding (0.1% vs. 0.6%, P = 0.218) was numerically lower., Conclusion: In diabetic patients undergoing PCI, bivalirudin was significantly associated with reduced risks of 30-day NACE and MACCE, mainly driven by the lower rates of bleeding and mortality, compared with heparin monotherapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jing Li et al.)

Objectives: Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited., Design: Retrospective cohort study., Setting: Single tertiary-quaternary referral center., Patients: All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020., Interventions: Not applicable., Measurements and Main Results: Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange., Conclusions: Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis., Competing Interests: Drs. Puri, Tunuguntla, Spinner, and Adachi disclosed the off-label product use of HeartWare HVAD for ventricular assist device support. Drs. Puri, Tunuguntla, Hensch, and Teruya disclosed the off-label product use of bivalirudin for first-line anticoagulation. Dr. Adachi reported consultant/proctor for Berlin Heart, Medtronic, Abbott, Abiomed, Jarvik, BiVACOR, and Sony-Olympus Medical Solutions. Dr. Teruya received funding from Hemosonics and UptoDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Heparin-induced thrombocytopenia (HIT) type-2 is a rare, but life-threatening complication that presents a unique challenge in patients undergoing cardiac surgery. Patients that require cardiac surgery with HIT present a dilemma between intraoperative anticoagulation, perioperative bleeding risk, and perioperative thrombotic events. We describe a case series of four patients who developed HIT in their hospital course before HeartMate 3 (HM3) left ventricular assist device implantation. Following a multidisciplinary approach, all patients did well intraoperatively with an approach of preoperative plasmapheresis, intraoperative unfractionated heparin (UFH), and postoperative conversion to bivalirudin with a bridge to warfarin. However, two patients had postoperative bleeding complications on bivalirudin. This case series details the therapeutic challenges encountered for HM3 implantation in patients with HIT and offers a therapeutic alternative to intraoperative bivalirudin in the effort to decrease perioperative complications in this challenging patient population., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH., Competing Interests: Disclosure: The authors have no financial or conflicts of interest to report., (Copyright © ASAIO 2021.)

Background: This prospective, multi-center, intensive monitoring study aimed to systematically assess the occurrence of adverse events (AEs) and adverse drug reactions (ADRs), especially thrombocytopenia and bleeding, as well as their risk factors in Chinese ST-segment elevation myocardial infraction (STEMI) patients receiving bivalirudin as anticoagulant for percutaneous coronary intervention (PCI)., Methods: In total, 1244 STEMI patients undergoing PCI and receiving bivalirudin as anticoagulant were enrolled in the present study. Safety data were collected from hospital admission to 72 h after bivalirudin administration; in addition, patients were further followed up at the 30th day with safety data collected at that time., Results: AEs, severe AEs, ADRs and severe ADRs were reported in 224 (18.0%), 15 (1.2%), 49 (3.9%) and 5 (0.4%) patients, respectively. Importantly, 4 (0.3%) patients were submitted to hospitalization and 6 (0.5%) patients died due to AEs, while 1 (0.1%) patient was submitted to hospitalization but no (0.0%) patient died due to ADRs. Meanwhile, thrombocytopenia and bleeding occurred in 24 (1.9%) and 21 (1.7%) patients, respectively. Further multivariate logistic analysis identified several important independent factors related to AEs, ADRs, thrombocytopenia or bleeding, which included history of cardiac surgery and renal function impairment, high CRUSADE risk stratification, elective operation and combination with glycoprotein IIb/IIIa inhibitors. Moreover, 4 multivariate models were constructed based on the above-mentioned factors, which all showed acceptable predictive value for AEs, ADRs, thrombocytopenia and bleeding, respectively., Conclusion: Bivalirudin is a well-tolerant anticoagulant in Chinese STEMI patients undergoing PCI procedure., (© 2022. The Author(s).)

Objective: To assess the effectiveness and safety of bivalirudin compared with heparin monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI)., Background: Bivalirudin is recommended for periprocedural use in patients undergoing PCI who are of high bleeding risk. However, its safe and efficacious use in elderly patients, a typical high bleeding risk cohort, in real world practice is yet to be reported., Methods: In this single center, real-world observational study, 4736 consecutive elderly patients who underwent PCI were enrolled. Of these, 1240 were treated with bivalirudin and 3496 with heparin according to the periprocedural anticoagulation strategies of PCI. The primary outcome was 12-month net adverse clinical events (NACE) defined as a composite of cardiac death, myocardial infarction, stroke, revascularization, or any bleeding. Propensity score matching (PSM) was used to balance baseline characteristics between groups., Results: After PSM, bivalirudin was found to be associated with lower rates of NACE (19.1% vs. 24.7%, p = 0.002), cardiac death (2.7% vs. 4.3%, p = 0.038), and any bleeding (10.0% vs. 12.9%, p = 0.023) compared to heparin monotherapy. No differences were found in the incidences of myocardial infarction, stroke, revascularization, stent thrombosis (0.1% vs. 0.1%, p = 1.000), and major bleedings (0.5% vs. 0.5%, p = 1.000) between the two patient groups., Conclusion: In this real-world observational study, periprocedural use of bivalirudin in elderly patients who underwent PCI was associated with less cardiac death and any bleeding compared to heparin monotherapy, without increased risk of stent thrombosis., (© 2022 Wiley Periodicals LLC.)

Background: The present study aimed to comprehensively investigate the occurrence and risk factors of adverse events (AEs) or adverse drug reactions (ADRs) (especially for thrombocytopenia and bleeding) in Chinese female patients receiving bivalirudin during percutaneous coronary intervention (PCI)., Methods: A total of 918 female patients from 27 Chinese medical centers took bivalirudin as anticoagulant for PCI were enrolled in this prospective, multi-center, intensive monitoring study. Safety data (AEs, ADRs, thrombocytopenia and bleeding) were collected from admission to 72 h post bivalirudin administration; then, patients were followed up at the 30 th day with the safety data collected as well., Results: One hundred and twenty (13.1%) patients occurred AEs, among which 7 (0.8%) cases experienced severe AEs, and 2 (0.2%) cases died. Besides, 40 (4.4%) patients occurred bivalirudin-related ADRs, in which 3 (0.3%) cases experienced severe ADRs, but 0 (0.0%) cases died. It was of note that 27 (2.9%) and 13 (1.4%) patients experienced thrombocytopenia and bleeding, respectively. Subsequent multivariate analyses observed that: clinical presentation of spontaneous coronary artery dissection (SCAD) (odds ratio (OR) = 3.191, P = 0.004), CRUSADE high risk (OR = 2.075, P = 0.031), multiple culprit vessel (OR = 2.328, P = 0.019) independently correlated with higher risk of bivalirudin-related ADRs; clinical presentation of SCAD (OR = 4.388, P = 0.002) and multiple culprit vessel (OR = 2.974, P = 0.010) independently linked with raised thrombocytopenia risk; history of diabetes mellitus (OR = 5.227, P = 0.007) and CRUSADE high risk (OR = 4.475, P = 0.016) were independent factor related to elevated bleeding risk., Conclusion: Bivalirudin is well tolerated with low ADRs, thrombocytopenia and bleeding incidences in Chinese female patients undergoing PCI., (© 2022. The Author(s).)

Objective: The present study aimed to investigate the application safety of bivalirudin combined with ticagrelor in the emergency percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: From October 1, 2018, to December 30, 2019, 210 patients with STEMI admitted to the Department of Cardiology who underwent emergency PCI were randomly divided into the bivalirudin group (group A, N = 105) and the unfractionated heparin group (group B, N = 105). Before the emergency PCI operation after admission, the loading dose of aspirin (300 mg) was given orally, and then 100 mg/d. At the same time, the loading dose of ticagrelor (180 mg) was administered orally, and then 90 mg/bid. The adverse events and the hemorrhage events 30 days after the operation were observed and recorded., Results: There were five hemorrhage cases in the bivalirudin group, with one case of secondary hemorrhage and four cases of mild hemorrhage. There were 14 hemorrhages in the unfractionated heparin group with one case of secondary hemorrhage and thirteen cases of mild hemorrhage. In terms of mild hemorrhage, the hemorrhage rate in the bivalirudin group was significantly lower than that in the unfractionated heparin group (3.8% vs. 12.4%, P = 0.040). One patient died in the unfractionated heparin group, while no deaths occurred in the bivalirudin group during the thirty days of follow-up. No myocardial infarction, revascularization, or stroke occurred in the two groups within 30 days after the operation., Conclusion: Compared with unfractionated heparin combined with ticagrelor in patients with STEMI undergoing emergency PCI treatment, bivalirudin combined with ticagrelor could significantly reduce the occurrence of mild hemorrhage events, and it would not increase the incidence of MACE during the 30 days of follow-up.

Background: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y 12 -inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry)., Methods: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days., Results: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y 12 -inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P =0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P =0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P =0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P =0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P =0.04)., Conclusions: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y 12 -inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Background and Aim: Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency., Methods: A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI., Results: No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group., Conclusion: Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.

Abstract: Bivalirudin and heparin are the principal anticoagulants used during primary percutaneous coronary intervention (PCI) for patients experiencing ST-elevation myocardial infarctions. Based on previous meta-analyses, bivalirudin improves 30-day mortality rates compared with heparin, especially when vascular access is predominantly femoral. However, no meta-analysis has yet reported whether this mortality benefit with bivalirudin persists beyond 30 days. Scientific databases and websites were searched to find randomized controlled trials, and risk ratios (RRs) were calculated using random effect models. Data from 4 trials were analyzed. Compared with heparin ± glycoprotein IIb/IIIa inhibitors, bivalirudin decreased all-cause mortality [RR, 0.81; 95% confidence interval (CI), 0.69-0.94; P = 0.008], cardiac mortality (RR, 0.72; 95% CI, 0.60-0.88; P = 0.001), and net adverse clinical events (RR, 0.83; 95% CI, 0.72-0.97; P = 0.016) at 1 year. In conclusion, a bivalirudin-based anticoagulation strategy during primary percutaneous coronary intervention significantly decreases the 1-year risks for all-cause mortality, cardiac mortality, and net adverse clinical events compared with heparin ± glycoprotein IIb/IIIa inhibitor., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support., Design: Retrospective cohort study., Setting: Single-center, cardiothoracic ICU., Patients: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020., Internventions: IV bivalirudin or IV unfractionated heparin., Measurements and Main Results: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001., Conclusions: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered., Competing Interests: Dr. Gomez’s institution received funding from TES Pharma. Dr. Arlia disclosed off-label product use of extracorporeal membrane oxygenation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

This meta-analysis was performed to compare the safety, efficacy, and pharmacoeconomic of bivalirudin versus heparin in high-risk patients for percutaneous coronary interventions (PCI). Earlier meta-analysis comparing bivalirudin and heparin during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. However, little data were available on the safety of bivalirudin versus heparin in high-risk patients for PCI. Thus, we performed a meta-analysis to evaluate the efficacy and safety in the "high-risk" patients. A systematic search of electronic databases was conducted up to July 30, 2020. The Cochrane Risk of Bias assessment tool was used to assess the quality of included studies. The primary outcomes were all-cause death and major adverse cardiac events (MACE); secondary outcomes were major and minor bleeding, followed by a cost-minimization analysis comparing bivalirudin and heparin using a local drug and medical costs reported in China. Subgroup analysis was based on the type of disease of the high-risk population. Finally, a total of 10 randomized controlled trials involved 42,699 patients were collected. The Cochrane Risk of Bias Tool was employed to appraise the research quality. No significant difference was noted between bivalirudin and heparin regarding all-cause death and MACE. However, subgroup analysis showed that bivalirudin caused less major bleeding in female (OR:0.65, 95% CI:0.53-0.79), diabetes (OR:0.55, 95%CI:0.42-0.73), and CKD (OR:0.59, 95%CI:0.63-1.65). The scatterers of the included literature were approximately symmetrical, and no research was outside the funnel plot. Additionally, cost-minimization analysis showed that heparin was likely to represent a cost-effective option compared with bivalirudin in China, with potential savings of 2129.53 Chinese Yuan (CNY) per patient for one PCI. Overall, the meta-analysis showed that although bivalirudin appeared to have a lower risk of major bleeding rate, the overall effectiveness and safety between the two groups showed no significant difference in high-risk patients for PCI. But the results of the cost-minimization analysis showed that heparin could be a potential cost-saving drug than bivalirudin in patients for PCI in China., (© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR)., Objective: We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial., Methods: The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR., Results: The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08)., Conclusion: In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.

Purpose: Bivalirudin as a thrombin inhibitor is proven to have a low risk of bleeding during percutaneous coronary intervention (PCI). Some evidence indicates comparable effectiveness and safety between bivalirudin and unfractionated heparin (UFH). Although bivalirudin during PCI offers more clinical and safety benefits to patients with chronic total occlusion (CTO), mostly via radial access, this has not been confirmed. The objective of this study was to examine the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) in patients with CTO., Methods: This trial used a retrospective cohort study design. Medical information from 736 patients with CTO who underwent PCI with bivalirudin or UFH at the First Affiliated Hospital of Zhengzhou University from July 2019 to September 2020 was extracted and analyzed. The primary end point was the 30-day incidence of net adverse clinical events (NACEs), and the secondary end point was the major adverse cardiovascular events (MACEs), which were related to safety and efficacy, respectively. Other end points incorporated each component of the primary outcome, target vessel revascularization, and stent thrombosis. Clinical and procedural characteristics at baseline were adjusted by using a logistic regression model., Findings: Overall, 71.5% of patients with CTO used the radial approach. Both groups exhibited nonsignificant differences in the majority of baseline characteristics. The bivalirudin group was associated with a significant reduction in NACEs (12.9% vs 21.5%; P = 0.002) and major bleeding (2.5% vs 8.0%; P = 0.001) versus the UFH group at the end of the 30-day follow-up. The incidence of MACEs, myocardial infarction, death, stroke, stent thrombosis, and target vessel revascularization did not differ significantly between the 2 groups. Moreover, the bivalirudin group also reported a lower incidence of NACEs in the prespecified subgroups., Implications: Bivalirudin exhibited comparative efficacy but superior safety compared with UFH among patients with CTO undergoing PCI. Chinese Clinical Trial Registry: ChiCTR2000034771., Competing Interests: Disclosures The authors have indicated that they have no conflicts of interest regarding the content of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Given the adverse event rates involving bleeding and thrombosis among children on ventricular assist devices (VADs), anticoagulant management has become a focal point for quality improvement and innovation. There may be advantages to using direct thrombin inhibitors, such as bivalirudin, though this has not been fully explored. As the percent time in therapeutic range (%TTR) for anticoagulants is classically associated with improved clinical outcomes, we evaluated the %TTR for bivalirudin among pediatric VAD recipients. Using a modification of the Rosendaal method, %TTR was calculated using activated partial thromboplastin time measurements for 11 VAD recipients in the early postoperative period (postoperative days 0-14) and for the duration of VAD support. In the initial 2 weeks after VAD implant, mean %TTR was 68.7 (±13.0). During the entire support course, the mean %TTR improved to 79.6 (±11.0). There was an era effect with improving %TTR in the latter half of the study period. We report very good %TTR for bivalirudin both in the first 2 weeks post implant and this improved over the duration of support. Because %TTR reflects the degree of safety and efficacy in chronic anticoagulation, this relatively high %TTR among a diverse, often critically ill cohort suggests that bivalirudin may be a promising agent. Although this study was underpowered to comprehensively evaluate adverse events on bivalirudin, this represents an important next step for larger scale study., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2021 by the ASAIO.)

Abstract: The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To investigate the efficacy and safety of hirudin plus aspirin therapy compared with warfarin in the secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation (NVAF). Methods: Patients with cardioembolic stroke due to NVAF were prospectively enrolled from 18 collaborating hospitals from Dec 2011 to June 2015. Fourteen days after stroke onset, eligible patients were assigned to the hirudin plus aspirin group (natural hirudin prescribed as the traditional Chinese medicine Maixuekang capsule, 0.75 g, three times daily, combined with aspirin 100 mg, once daily) or the warfarin group (dose-adjusted warfarin targeting international normalized ratio (INR) 2-3, with an initial daily dose of 1.25 mg). Patients were followed up at 1, 2, 3, 6, 9, and 12 months after stroke onset. Time in therapeutic range (TTR) was calculated according to Rosendaal methodology to evaluate the quality of INR management in the warfarin group. The primary efficacy endpoint was the recurrence of stroke within 12 months after stroke onset. Safety was assessed as the occurrence of the composite event "intracranial hemorrhage and other bleeding events, death, and other serious adverse events". The Cox proportional hazard model and Kaplan-Meier curve were used to analyze the efficacy and safety events. Results: A total of 221 patients entered final analysis with 112 patients in the hirudin plus aspirin group and 109 in the warfarin group. Over the whole duration of our study, TTR for patients taking warfarin was 66.5 % ± 21.5%. A significant difference was not observed in the recurrence of stroke between the two groups (3.57% vs. 2.75%; P = 0.728). The occurrence of safety events was significantly lower in the hirudin plus aspirin group (2.68% vs.10.09%; P = 0.024). The risk for efficacy event was similar between the two groups (hazard ratio (HR), 1.30; 95% confidence interval (CI), 0.29-5.80). The safety risk was significantly lower in the hirudin plus aspirin group (HR, 0.27; 95% CI, 0.07-0.95). Kaplan-Meier analysis revealed significant difference in the temporal distribution in safety events ( P = 0.023) but not in stroke recurrence ( P = 0.726). Conclusion: Significant difference in efficacy was not detected between warfarin group and hirudin plus aspirin group. Compared with warfarin, hirudin plus aspirin therapy had lower safety risk in the secondary prevention of cardioembolic stroke due to NVAF., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Although heparin has previously been the anticoagulant of choice during mechanical circulatory support (MCS), there is a lack of consistency in dose-response in pediatric patients. Bivalirudin offers more consistent dose-response in adults; however, there are limited data for pediatrics use., Objective: The purpose was to characterize the usage, dosage, and safety profile of bivalirudin when used for pediatric MCS in a tertiary care pediatric hospital., Methods: A retrospective review of pediatric patients receiving bivalirudin for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) anticoagulation was conducted. The primary outcome was the average dose of bivalirudin. Additional outcomes included initial and maximum bivalirudin dose, time to first therapeutic activated partial thromboplastin time (aPTT), time within goal aPTT range, bleeding and clotting complications, and cost. Data were compared between ECMO and VAD patients., Results: Thirty-four patients were included. The median dose of bivalirudin was 0.37 mg/kg/h (interquartile range [IQR] = 0.21-0.56), with a maximum dose of 0.62 mg/kg/h (IQR = 0.33-0.91). VAD patients had a higher median and maximum dose as compared with ECMO patients. Patients achieved their therapeutic goal in a median of 6.1 hours and averaged 61.9% time within therapeutic aPTT. One patient had significant hemorrhage, whereas 3 patients had clotting requiring a circuit change. Bivalirudin acquisition cost was higher than heparin., Conclusion and Relevance: Bivalirudin dosing in ECMO and VAD patients is consistent with dosing seen in previous reports but may be higher in VAD patients. Comparative studies between heparin and bivalirudin are necessary to compare cost-effective outcomes for pediatric patients.

There is a paucity of data regarding the use of direct thrombin inhibitors such as bivalirudin for children on extracorporeal life support (ECLS). We sought to compare the outcomes of children on ECLS anticoagulated with bivalirudin versus heparin. Patients transitioned from heparin to bivalirudin were treated as a separate group. A single-institution, retrospective review of all consecutive children (neonate to 18 years) placed on ECLS in the cardiac or pediatric intensive care units was performed (June 2018-December 2019). Data collected included demographics, anticoagulation strategy, number of circuit interventions, blood product use on ECLS, survival to decannulation, and survival to discharge. Fifty-four children were placed on ECLS for a total of 56 runs. Demographics and venovenous versus venoarterial ECLS were similar. The bivalirudin group had longer median duration of support compared to the heparin group--11.0 days [IQR 6.2, 23.1] versus 3.3 days [2.1, 6.2], P < .001. Patients switched from heparin to bivalirudin had a similar duration of support (10.3 days [8.3, 18.3]) as those on bilvalirudin alone. However, there was no difference in red blood cell, fresh frozen plasma, or platelet transfusions. There was no difference in the number of circuit interventions, survival to decannulation or discharge. The freedom to first circuit intervention was longer with bivalirudin compared to heparin. Our data suggest that even with longer pediatric ECLS runs on bivalirudin, there were no differences in the outcomes between the heparin and bivalirudin groups, with longer freedom from first circuit intervention with bivalirudin. While this is the largest reported series comparing children on ECLS anticoagulated with heparin versus bivalirudin, larger studies are needed to determine the optimal anticoagulation strategy for this diverse and complicated group of children., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: Residual stent strut thrombosis after primary percutaneous coronary intervention (PCI), negatively affects myocardial perfusion, may increase stent thrombosis risk, and it is associated with neointima hyperplasia at follow-up., Objectives: To study the effectiveness of any bivalirudin infusion versus unfractionated heparin (UFH) infusion in reducing residual stent strut thrombosis in patients with ST-elevation myocardial infarction (STEMI)., Methods: Multi-vessel STEMI patients undergoing primary PCI and requiring staged intervention were selected among those randomly allocated to two different bivalirudin infusion regimens in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Those receiving heparin only were enrolled into a registry arm. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of primary PCI and 3-5 days thereafter during a staged intervention. The primary endpoint was the change in minimum flow area (ΔMinFA) defined as (stent area + incomplete stent apposition [ISA] area) - (intraluminal defect + tissue prolapsed area) between the index and staged PCI., Results: 123 patients in bivalirudin arm and 28 patients in the UFH arm were included. Mean stent area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The ΔMinFA in the bivalirudin group was 0.25 versus 0.05 mm 2 in the UFH group, which resulted in a between-group significant difference of 0.36 [95% CI: (0.05, 0.71); p = .02]. This was mostly related to a decrease in tissue protrusion in the bivalirudin group (p = .03). There was a trend towards more patients in the bivalirudin group who achieved a 5% difference in the percentage of OCT frames with the area >5% (p = .057)., Conclusions: The administration of bivalirudin after primary PCI significantly reduces residual stent strut thrombosis when compared to UFH. This observation should be considered hypothesis-generating since the heparin-treated patients were not randomly allocated., (© 2019 Wiley Periodicals, Inc.)