What Is the Optimal Antithrombotic Therapy for Valsalva Thrombus Following Transcatheter Aortic Valve Replacement?

Thrombus formation between the native sinus of Valsalva and the implanted transcatheter heart valve is a rare complication that may be associated with an increased risk for thrombotic complications. This paper presents the course of 3 cases with Valsalva thrombus, with a focus on the management of antithrombotic therapy.

Antithrombotic Therapy in Patients with Complex Percutaneous Coronary Intervention and Cardiogenic Shock.

Managing antithrombotic therapy in patients undergoing complex and high-risk in indicated patients, including those treated with complex percutaneous coronary intervention (PCI) or presenting with cardiogenic shock (CS), is challenging. This review highlights the critical role of antithrombotic therapy, during and after PCI, to optimize the efficacy while minimizing risks. Unfractionated heparin remains the mainstay anticoagulant for complex PCI and CS, with bivalirudin as a potential safer alternative. Cangrelor offers consistent antiplatelet effects, especially when timely absorption of oral agents is uncertain.

Antiplatelet Therapy in Patients Requiring Oral Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Antithrombotic Therapy in Patients Undergoing Percutaneous Left Atrial Appendage Occlusion.

Percutaneous left atrial appendage closure (LAAC) is a valid alternative to oral anticoagulation to prevent ischemic stroke in patients with atrial fibrillation.The devices approved in Europe and United States for percutaneous LAAC contain metal and temporary antithrombotic therapy is strongly recommended following implantation to prevent thrombus formation on the atrial device surface. There is still uncertainty regarding to the optimal antithrombotic drug regimen after device implantation for several reasons. Thus, this review aims at summarizing the available evidence and the remaining challenges related to the management of antithrombotic therapy in the context of LAAC procedure.

Antithrombotic Therapy in Patients Undergoing Peripheral Artery Interventions.

Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.

Antithrombotic Strategies With Left Ventricular Assist Devices.

Long-term outcomes of patients with advanced heart failure treated with durable left ventricular assist devices (LVADs) have been augmented due to improved durability and hemocompatibility on the backbone of pump engineering enhancements. The incidence of hemocompatibility-related adverse events (pump thrombosis, stroke and nonsurgical bleeding events) are device specific and vary by type of engineered pump. A fully magnetically levitated rotor containing LVAD in concert with use of antithrombotic therapy has successfully overcome an increased risk of pump thrombosis and stroke-risk, albeit with only modest reduction in bleeding events. Modifications to antithrombotic strategies have focused on reduced-dose vitamin K antagonist use or use of direct oral anticoagulants with demonstration of safety and progress in reduction of mucosal bleeding episodes with elimination of antiplatelet agents. This review outlines the current landscape of advances in anticoagulation management in LVAD patients, highlighting the need for ongoing research and cautious application of emerging therapies and technologies.

[GDF-15 and the risk of bleeding in patients with stable CAD receiving multicomponent antithrombotic therapy: the results of the prospective REGATA register].

AIM: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. RESULTS: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. CONCLUSION: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Spontaneous mesenteric hematoma occurring during antithrombotic therapy and responsive to surgical treatment: a case report.

BACKGROUND: Spontaneous mesenteric hematoma is a rare condition that is diagnosed when clinical and pathological findings do not identify an obvious causative disease. Various treatment options for spontaneous mesenteric hematoma exist; however, there are no clear treatment criteria. Herein, we report a case of spontaneous mesenteric hematoma that was successfully treated surgically and discuss the optimum treatment strategy based on similar cases. CASE PRESENTATION: A 63-year-old man with abdominal persisting for 3 days presented to our hospital after going into shock without any triggers. The patient had a history of atrial fibrillation, stroke, and an aneurysm, and was receiving antithrombotic therapy. Abdominal contrast-enhanced computed tomography revealed a mass structure within the sigmoid mesentery, which was suspected to be a hematoma. The patient was admitted to the hospital for follow-up observation after initial infusion and vital stabilization. However, the following day, the patient developed acute generalized peritonitis with necrosis of the sigmoid colon; therefore, emergency Hartmann's surgery was performed. Intraoperative and histopathological examinations revealed no evidence of bleeding. CONCLUSION: Spontaneous mesenteric hematomas tend to be associated with intestinal necrosis and may require surgical treatment with bowel resection owing to the difficulty in identifying the responsible vessel. Moreover, our results suggest that the presence of antithrombotic therapy may be an important factor affecting spontaneous mesenteric hematoma development.

Impact of Preoperative Continued Aspirin Therapy on Perioperative Bleeding Complications in Patients Undergoing Gastrectomy for Malignancy.

Background The question of whether antiplatelet therapy (APT) should be discontinued prior to gastrectomy is controversial. In this study, we investigated the impact of continuing aspirin preoperatively on perioperative bleeding and thromboembolic complications in patients receiving gastrectomy for malignancy. Methods The study cohort comprised 1001 patients with malignant gastric tumors who had undergone gastrectomy between 2005 and 2021. This study excludes emergency surgery. The patients were allocated to the following three groups: those who continued aspirin monotherapy prior to surgery (cAPT group), those who stopped receiving it seven days prior to surgery (dAPT group), and those who did not take APT at any stage (non-APT group). The differences between the groups in intraoperative and postoperative complications, such as bleeding and thromboembolism, were examined. Results The non-APT group comprised 682 patients, the dAPT group had 164, and the cAPT group had 155. There were 22 bleeding events (2.2%) in the whole cohort, 11 (1.1%) of which occurred in the non-APT group, six (3.7%) in the dAPT group, and five (3.2%) in the cAPT group. The differences between the three groups were not significant in terms of bleeding complications. There were 10 (1.0%) thromboembolic events in the whole cohort, five (0.7%) of which occurred in the non-APT group, four (2.4%) in the dAPT group, and one (0.6%) in the cAPT group. The differences between the three groups were not significant in terms of thromboembolic complications. In a multivariate analysis of the whole cohort, intraoperative blood loss (≥1000 mL) (p < 0.001, odds ratio (OR) = 11.8) and multidrug APT (p < 0.001, OR = 7.8) were both independent predictors of bleeding complications. However, continuing to take aspirin before surgery was not a risk factor for bleeding complications. Conclusions In patients with malignant gastric tumors, preoperative continuation of aspirin monotherapy has no impact on either intraoperative or postoperative bleeding. Gastrectomy can be performed safely, even in patients who continue aspirin treatment.

Right Atrial Mass Discovered During Routine Follow-Up After Cardiac Procedures: Diagnostic Challenges and Management.

Cardiac masses pose significant diagnostic and therapeutic challenges in clinical practice. A 73-year-old male with a history of atrial fibrillation and percutaneous atrial septal defect (ASD) closure presented with an asymptomatic right atrial mass detected during routine transthoracic echocardiography follow-up. The mass measured 17 mm, with highly echoic peripheral areas and a heterogenous, low-echoic interior. The patient was asymptomatic and had no fever, embolic, or neurological symptoms. Multimodal imaging, including contrast-enhanced computed tomography, magnetic resonance imaging, and transesophageal echocardiography, revealed a mobile nodular mass in the right atrium (RA); however, the results of each modality were not consistently suggestive of a specific disease. The presumptive diagnosis of thrombus was made based on the change and variability of echocardiographic findings over time and the response to antithrombotic medications. Anticoagulant therapy with edoxaban led to the complete resolution of the mass, confirming the diagnosis of a thrombus. This case highlights the importance of multimodal imaging and temporal changes in findings in the diagnosis and management of RA masses and underscores the need for careful thrombotic risk assessment in patients with a history of atrial fibrillation, ASD, and cardiac procedures.

Safety and efficacy of percutaneous biopsy and microwave ablation in patients with pulmonary nodules on antithrombotic therapy: A study with rivaroxaban bridging.

BACKGROUND: To evaluate the safety and efficacy of percutaneous biopsy and microwave ablation (B + MWA) in patients with pulmonary nodules (PNs) who are receiving antithrombotic therapy by rivaroxaban as bridging therapy. METHODS: The study comprised 187 patients with PNs who underwent 187 B + MWA sessions from January 1, 2020, to December 31, 2021. The enrolled patients were divided into two groups: Group A, who received antithrombotic therapy five days before the procedure and received rivaroxaban as a bridging drug during hospitalization, and group B, who had no antithrombotic treatment. Information about the technical success rate, positive biopsy rate, complete ablative rate, and major complications were collected and analyzed. RESULTS: Group A comprised 53 patients and group B comprised 134 patients. The technical success rate was 100% in both groups. The positive biopsy rates were 88.68% and 91.04%, respectively (p = 0.6211, X2 = 0.2443). In groups A and B, the complete ablative rates at 6, 12, and 24 months were 100.0% versus 99.25%, 96.23% versus 96.27%, and 88.68% versus 89.55%, respectively. There were no significant differences in bleeding and thrombotic complications between the two groups. No grade 5 complications occurred. CONCLUSIONS: It is generally considered safe and effective that patients who are on antithrombotic therapy by rivaroxaban as bridging to undergo B + MWA for treating PNs.

Treatment of Transcatheter Aortic Valve Thrombosis: JACC Review Topic of the Week.

Transcatheter aortic valve (TAV) thrombosis may manifest as subclinical leaflet thrombosis (SLT) and clinical valve thrombosis. SLT is relatively common (10%-20%) after transcatheter aortic valve replacement, but clinical implications are uncertain. Clinical valve thrombosis is rare (1.2%) and associated with bioprosthetic valve failure, neurologic or thromboembolic events, heart failure, and death. Treatment for TAV thrombosis has been understudied. In principle, anticoagulation may prevent TAV thrombosis. Non-vitamin K oral anticoagulants, as compared to antiplatelet therapy, are associated with reduced incidence of SLT, although at the cost of higher bleeding and all-cause mortality risk. We present an overview of existing literature for management of TAV thrombosis and propose a rational treatment algorithm. Vitamin K antagonists or non-vitamin K oral anticoagulants are the cornerstone of antithrombotic treatment. In therapy-resistant or clinically unstable patients, ultraslow, low-dose infusion of thrombolytics seems effective and safe and may be preferred over redo-transcatheter aortic valve replacement or explant surgery.

Antithrombotic Strategies for Patients With Peripheral Artery Disease: JACC Scientific Statement.

Patients with peripheral artery disease (PAD) experience major cardiovascular and limb events. Antithrombotic strategies including antiplatelets and anticoagulants remain a cornerstone of treatment and prevention. Recent trials have shown heterogeneity in the response to antithrombotic therapies in patients presenting primarily with PAD when compared to those presenting primarily with coronary artery disease. In addition, there is observed heterogeneity with regards to the effects of antiplatelets and anticoagulants with respect to different outcomes including cardiovascular and major adverse limb events. This, coupled with risks of bleeding, requires a patient-centered and holistic assessment of benefit-risk when selecting antithrombotic strategies for patients with PAD. A global multidisciplinary work group was convened to evaluate antithrombotic strategies in PAD and to summarize the current state of the art. Common clinical scenarios around antithrombotic decision making were provided. Finally, insights with regard to implementation future investigation were described.

Association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation.

BACKGROUND: The impact of post-stroke antithrombotic regimen in atrial fibrillation is uncertain. OBJECTIVE: This study aimed to describe antithrombotic therapy prescribing patterns after ischemic stroke and the impact on outcomes. METHODS: A total of 23,165 patients with atrial fibrillation experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage, major bleeding, mortality, and composite outcomes. RESULTS: Of those who were nonanticoagulated before a stroke, 33.5% remained nonanticoagulated and 39.2% were prescribed only antiplatelet agents (APs) after a stroke. Compared with non-vitamin K antagonist oral anticoagulants (NOACs) after stroke, there was a significant increase in ischemic stroke and mortality in nonanticoagulated patients (adjusted hazard ratio [aHR], 2.09 and 3.92) and AP users (aHR, 1.32 and 1.28). Post-stroke warfarin was associated with a significantly increased risk of major bleeding compared with NOACs (aHR, 1.23). Of 769 patients receiving NOACs before stroke and continuing NOACs after stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR, 2.07) and composite outcomes (aHR, 1.36-1.85) with no difference in intracranial hemorrhage, major bleeding, or mortality compared with those receiving the same NOAC after stroke. Of patients receiving NOACs before stroke, the risks of clinical events were similar between patients taking NOACs alone and those taking NOAC plus AP after stroke. CONCLUSION: NOAC alone after stroke was associated with a better clinical outcome compared with nonanticoagulation, AP, or warfarin. Of patients already taking NOACs before stroke, the addition of AP did not confer additional benefits compared with NOACs alone. A change of NOAC types after stroke was associated with a 2-fold higher risk of ischemic stroke and composite outcomes.

Antithrombotic Therapy in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy.

BACKGROUND: Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph. SUBJECTIVE: The purpose of this study was to identify the potential lymph biomarkers for TIH. METHODS: Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. RESULTS: A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. CONCLUSIONS: This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.

Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome.

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.

Short-term Functional Outcomes and Treatment Trends between Branch Atheromatous Disease and Lacunar Infarction: Retrospective Cohort Study of the Nationwide Multicenter Registry.

Background: Branch atheromatous disease (BAD) is a form of ischemic stroke that presents with imaging findings similar to those of lacunar infarction, but has a different pathogenesis and is known to cause progressive paralysis. Due to regional variations, the epidemiology of BAD is not wellunderstood, and its relationship with functional prognosis remains unclear. Using a comprehensive Japanese stroke database, we investigated its epidemiological characteristics and associations with functional outcomes. Methods: In this multicenter cohort study, we retrospectively analyzed data from the Saiseikai Stroke Database (2013-2021) including 27 hospitals. We used multivariable logistic regression to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of BAD compared with LI for functional outcomes at discharge. Ischemic stroke caused by BAD or LI was included and demographic characteristics and clinical data were evaluated and contrasted between BAD and LI. Results: Of the 5,966 analyzed patients, 1,549 (25.9%) had BAD and 4,434 (74.1%) had LI. BAD was associated with worse functional outcomes (adjusted OR of 2.77, 95%CI: 2.42-3.17, relative to LI) and extended hospital stays (median 19 days for BAD vs. 13 days for LI). Moreover, aggressive treatment strategies, including the use of argatroban and dual antiplatelet therapy, were more common in BAD patients. Conclusions: BAD presented worse functional outcomes and longer hospital stays than LI, necessitating treatment plans that take into account its progression and prognosis.

Traumatic brain injury in elderly population: A global systematic review and meta-analysis of in-hospital mortality and risk factors among 2.22 million individuals.

BACKGROUND: Traumatic brain injury (TBI) among elderly individuals poses a significant global health concern due to the increasing ageing population. METHODS: We searched PubMed, Cochrane Library, and Embase from database inception to Feb 1, 2024. Studies performed in inpatient settings reporting in-hospital mortality of elderly people (≥60 years) with TBI and/or identifying risk factors predictive of such outcomes, were included. Data were extracted from published reports, in-hospital mortality as our main outcome was synthesized in the form of rates, and risk factors predicting in-hospital mortality was synthesized in the form of odds ratios. Subgroup analyses, meta-regression and dose-response meta-analysis were used in our analyses. FINDINGS: We included 105 studies covering 2217,964 patients from 30 countries/regions. The overall in-hospital mortality of elderly patients with TBI was 16 % (95 % CI 15 %-17 %) from 70 studies. In-hospital mortality was 5 % (95 % CI, 3 %-7 %), 18 % (95 % CI, 12 %-24 %), 65 % (95 % CI, 59 %-70 %) for mild, moderate and severe subgroups from 10, 7, and 23 studies, respectively. A decrease in in-hospital mortality over years was observed in overall (1981-2022) and in severe (1986-2022) elderly patients with TBI. Older age 1.69 (95 % CI, 1.58-1.82, P < 0.001), male gender 1.34 (95 % CI, 1.25-1.42, P < 0.001), clinical conditions including traffic-related cause of injury 1.22 (95 % CI, 1.02-1.45, P = 0.029), GCS moderate (GCS 9-12 compared to GCS 13-15) 4.33 (95 % CI, 3.13-5.99, P < 0.001), GCS severe (GCS 3-8 compared to GCS 13-15) 23.09 (95 % CI, 13.80-38.63, P < 0.001), abnormal pupillary light reflex 3.22 (95 % CI, 2.09-4.96, P < 0.001), hypotension after injury 2.88 (95 % CI, 1.06-7.81, P = 0.038), polytrauma 2.31 (95 % CI, 2.03-2.62, P < 0.001), surgical intervention 2.21 (95 % CI, 1.22-4.01, P = 0.009), pre-injury health conditions including pre-injury comorbidity 1.52 (95 % CI, 1.24-1.86, P = 0.0020), and pre-injury anti-thrombotic therapy 1.51 (95 % CI, 1.23-1.84, P < 0.001) were related to higher in-hospital mortality in elderly patients with TBI. Subgroup analyses according to multiple types of anti-thrombotic drugs with at least two included studies showed that anticoagulant therapy 1.70 (95 % CI, 1.04-2.76, P = 0.032), Warfarin 2.26 (95 % CI, 2.05-2.51, P < 0.001), DOACs 1.99 (95 % CI, 1.43-2.76, P < 0.001) were related to elevated mortality. Dose-response meta-analysis of age found an odds ratio of 1.029 (95 % CI, 1.024-1.034, P < 0.001) for every 1-year increase in age on in-hospital mortality. CONCLUSIONS: In the field of elderly patients with TBI, the overall in-hospital mortality and its temporal-spatial feature, the subgroup in-hospital mortalities according to injury severity, and dose-response meta-analysis of age were firstly comprehensively summarized. Substantial key risk factors, including the ones previously not elucidated, were identified. Our study is thus of help in underlining the importance of treating elderly TBI, providing useful information for healthcare providers, and initiating future management guidelines. This work underscores the necessity of integrating elderly TBI treatment and management into broader health strategies to address the challenges posed by the aging global population. REVIEW REGISTRATION: PROSPERO CRD42022323231.