Glenzocimab, a platelet glycoprotein VI antagonist, is a novel agent that inhibits platelet activation and aggregation. Its safety was demonstrated in the ACTIMIS trial (Acute Ischemic Stroke Interventional Study; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03803007) for patients with stroke receiving thrombolysis, with or without mechanical thrombectomy, and results suggested a reduction in intracranial hemorrhages and mortality. The ACTISAVE trial was designed as a confirmatory study to evaluate the efficacy and safety of glenzocimab in acute ischemic stroke.

ACTISAVE (Acute Ischemic Stroke Study Evaluating Glenzocimab Used as Add-On Therapy Versus Placebo) was an international, randomized, double-blind, placebo-controlled phase 2/3 study in patients with stroke, treated by thrombolysis within 4.5 hours of symptoms onset with or without mechanical thrombectomy. The study was conducted at 54 primary and comprehensive stroke centers located in 10 countries. Patients were randomized 1:1 to glenzocimab (1000 mg-IV) or placebo. The primary outcome was the modified Rankin Scale (mRS) score of 4 to 6 at day 90. Key secondary outcome was the mRS score of 0 to 2 at day 90. Mortality, mRS shift, National Institutes of Health Stroke Scale score, quality of life, and safety outcomes were assessed.

Between September 2021 and October 2023, 438 patients were randomized, 421 treated, and included as randomized in the primary analysis set. Median age was 73 (63-80) years, and 43% were female. Thrombolysis was performed 2.3 hours (median) after symptom onset and followed by mechanical thrombectomy in 36% of patients. The assigned treatment began a median of 1.2 (interquartile range, 0.8-1.6) hours after thrombolysis initiation. Prethrombolysis National Institutes of Health Stroke Scale score median was 9 (6-15). At day 90, there was no statistically significant difference in the primary outcome between the treatment groups: the incidence of poor outcome (mRS score 4-6 versus 0-3) was 21.6% in the glenzocimab group compared with 15.3% placebo group (odds ratio, 1.51 [95% CI, 0.90-2.54]; P=0.120). No statistically significant difference in secondary outcomes was observed. There were no major safety signals with any intracerebral hemorrhage occurring respectively in 60 (28.6%) and 63 (29.9%) patients in glenzocimab and placebo arms.

ACTISAVE failed to confirm a beneficial effect of glenzocimab on mRS in patients with acute ischemic stroke treated by thrombolysis.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05070260.

Adverse pregnancy outcomes are linked to increased risk of maternal cardiovascular disease. However, the association between preterm delivery (PTD) and long-term risk of stroke in the mother remains uncertain, particularly in the case of spontaneous PTD.

A systematic review and meta-analysis were performed to provide an up-to-date synthesis of the evidence on the association between PTD and long-term maternal stroke. PubMed, CINAHL, and Web of Science were searched for relevant articles published between January 1, 2000, and May 6, 2025. Eligible studies included cohort and case-control studies examining populations of parous women. Primary exposure was defined as any PTD; secondary exposures were spontaneous PTD and medically indicated PTD. The primary outcome was defined as any stroke; secondary outcomes were ischemic and hemorrhagic stroke. Two reviewers screened studies, extracted data, and performed quality assessments. Pooled unadjusted and adjusted effect estimates (as defined by the original study) were calculated separately using random effects inverse variance models.

Eleven thousand twenty-five studies were screened for eligibility. Across 21 studies including a total of 8.7 million participants, PTD was consistently associated with increased stroke risk. The follow-up period ranged from 8 to 57 years. The primary meta-analysis demonstrated a positive association between any PTD and any stroke (adjusted risk ratio [aRR], 1.66 [95% CI, 1.34-2.05]). A high level of heterogeneity was observed (I²=97%, τ²=0.15), possibly due to variations in exposure definition, outcome ascertainment, and follow-up durations. Spontaneous PTD (aRR, 1.37 [95% CI, 1.15-1.64]) and medically indicated PTD (aRR, 2.08 [95% CI, 1.70-2.54]) were associated with any stroke. PTD was positively associated with ischemic (aRR, 1.59 [95% CI, 1.45-1.75]) and hemorrhagic stroke (aRR, 1.44 [95% CI, 1.06-1.94]).

Women who have experienced a PTD, including spontaneous PTD, may be at increased risk of stroke in later life. These women may benefit from targeted cardio-metabolic preventive interventions postpartum to reduce their risk.

Hard-to-control hypertension, comprising uncontrolled and resistant hypertension, is highly prevalent, meaning many patients with hypertension remain at risk of adverse outcomes despite treatment. To discuss the role of managed care in addressing hard-to-control hypertension, AMCP Market Insights virtually convened an expert panel of managed care stakeholders in November 2025. This article provides a qualitative summary of the panel discussion. Key insights were that despite multiple effective, low-cost pharmacotherapy options, a significant proportion of patients have blood pressure above recommended goals because of confounding factors at both the micro and macro levels; and managed care-specific challenges in hard-to-control hypertension include competing organizational priorities, data gaps, and lack of integration of existing resources. Opportunities to advance care in hard-to-control hypertension include focusing on prevention and providing additional patient and clinician support such as with education and enhancing use of digital technologies. Other insights were that top payer priorities in hypertension include reducing cardiovascular events and other complications and meeting quality goals, and that current clinical guidelines and provider input are important elements of payer decision-making. These findings can support informed clinical and coverage decisions, can offer practical actions for payers, and may inform future work.

Clopidogrel was added to the national formulary of the Veterans Health Administration (VHA) in 2000, with national guidance in the form of Criteria for Use (CFU) generated in 2007 by the Pharmacy Benefits Management office. Although the national CFU restricted the duration of clopidogrel to no more than 30 days following peripheral vascular intervention (PVI) for peripheral artery disease (PAD), each local VHA Veterans Affairs Medical Center (VAMC) determined its own strategies of implementation. Strategies ranged from passive diffusion of information to electronic health record-mandated pharmacist approval for noncompliant CFU prescribing.

To characterize patterns of compliance to restricted duration of clopidogrel and determine the factors associated with compliance.

In a retrospective cohort study, we used the Veterans Affairs Surgical Quality Initiative Program (2007-2022) to identify index PVI performed for PAD and integrated post-PVI medication information from the VA Clinical Data Warehouse. Our primary outcome was to evaluate compliance with the CFU. During the active CFU period (2007-2018), we compared patient, procedural, and VAMC features by CFU compliance and determined their associations with compliance using multivariable logistic regression. We also characterized variation in compliance across the Veterans Integrated Service Network (VISN), VAMC, and surgeons.

Among 7,206 PVIs with postoperative clopidogrel, 35% and 26% had post-PVI clopidogrel durations of no more than 30 days during and after the CFU period, respectively. During the active CFU period, we found no strong association among patient, PVI, and VAMC characteristics with compliance. Compliance during the active CFU period varied significantly among VISNs (16%-55%), VAMCs (0%-93%), and surgeons (0%-100%).

Adherence to no more than 30 days of clopidogrel post-PVI was low during and after the active CFU period and varied substantially among the VISNs, VAMCs, and surgeons. Given that national guidance implementation was directed by local VHA pharmacies, this study highlights the importance and limitations of local implementation strategies on national guidance compliance.

Over the past decade, colchicine has re-emerged as a promising therapeutic candidate for atherosclerotic cardiovascular disease. Here we review evidence from large randomized controlled trials together with advances in mechanistic research that have clarified how colchicine modulates vascular inflammation and plaque stability. Canonically, colchicine disrupts microtubule dynamics and suppresses NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation. Beyond these actions, it limits oxidative stress, modulates cytoskeletal cross-talk, attenuates cholesterol crystal formation and reprograms inflammatory and metabolic proteomic networks. Colchicine influences multiple vascular and immune cell types, including neutrophils, monocytes, macrophages, endothelial cells, smooth muscle cells and platelets, collectively reducing vascular inflammation and promoting plaque stability. Notably, while colchicine has demonstrated benefit in coronary artery disease, several recent trials in cerebrovascular disease have reported neutral outcomes, suggesting disease-specific inflammatory mechanisms and therapeutic responsiveness. Integrating mechanistic insights with clinical evidence will be critical to optimize colchicine use and advance precision anti-inflammatory strategies in atherosclerotic cardiovascular disease.

Measurements of blood sphingolipids have previously been shown to predict cardiometabolic risk beyond traditional biomarkers. However, before these scores can be implemented in clinical practice, it is essential to establish lifespan trajectories and age- and sex-specific values for sphingolipid levels. This cross-sectional study aimed to characterise sphingolipid levels in clinically healthy individuals across the lifespan.

Serum sphingolipids from 522 clinically healthy individuals aged 20 to 91 of the COmPLETE-Health study (48% females) were quantified using targeted liquid chromatography-tandem mass spectrometry. Associations between sphingolipids and age were assessed using multiple linear regressions adjusted for sex, cardiorespiratory fitness, and other confounding variables. Descriptive age- and sex-specific sphingolipid quantile curves were modelled using generalised additive models for location, scale, and shape.

Fourteen of the 21 detected sphingolipids were significantly and positively associated with age in both sexes. Notably, all four sphingolipids included in the Cardiovascular Event Risk Tests (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) increased with age, whereas their respective ratios were not significantly associated with age. Females exhibited significantly higher levels than males for four sphingomyelins, two ceramides, HexCer18:0, and the Cer16:0/Cer24:0 ratio. Age- and sex-specific values across the lifespan (20 to 90 years) are provided as percentiles. Associations between cardiorespiratory fitness and sphingolipid levels varied by species.

Serum sphingolipid levels depended on age, underscoring the need for age-specific interpretation when assessing cardiometabolic risk using sphingolipid-based scores. Conversely, sphingolipid ratios remained unaffected by age.

Atrial cardiomyopathy (ACMP) encompasses structural, electrical and functional atrial abnormalities that have been associated with ischaemic stroke, heart failure and mortality, independent of atrial fibrillation (AF). Increasing evidence suggests that AF, stroke and other adverse outcomes may represent parallel manifestations of ACMP. In the present narrative review, we synthesise current experimental and clinical evidence on the risk factors, pathophysiology, diagnosis and stages of ACMP, and summarise its bidirectional interactions with affected organs, including the left ventricle, lungs, brain, kidneys and gut.ACMP can be considered as an upstream disease process driven by fibrosis, inflammation, oxidative stress, hypercoagulability, metabolic stress and adipose tissue. Through haemodynamic, neurohormonal, inflammatory and thrombotic pathways, ACMP both contributes to and results from dysfunction in other organs, forming self-perpetuating cycles. ACMP can be characterised using complementary electrical, structural, functional and biomarker-based measures, although no single diagnostic standard exists. Disease progression appears staged, with earlier phases potentially reversible and advanced stages dominated by more permanent structural remodelling.Collectively, the evidence supports considering ACMP as a multiorgan disease, highlighting the need for an atrium-centred, integrated approach to risk stratification, preventive and therapeutic strategies.

Data on outcomes of patients complicating with Takotsubo syndrome (TTS) following stroke, contributing factors and prognosis significance have not been well characterised.

To assess the incidence, factors and prognosis of TTS-complicated stroke, and to determine the 30-day unplanned readmission rates with TTS and its prognosis among stroke survivors without initial TTS.

The US Nationwide Readmission Database was queried using International Classification of Disease codes to gather information on individuals hospitalised with primary diagnosis of stroke between January 2010 and November 2021. Incidence, factors and prognosis associated with TTS-complicated stroke and 30-day unplanned readmissions with new TTS were assessed. The primary outcome was the occurrence of death during index admission for stroke as well as during readmission episode with TTS. Incidence, factors and prognosis associated with TTS-complicated stroke and 30-day unplanned readmissions with new TTS were assessed.

Of 3 376 606 patients admitted with primary diagnosis of stroke, 6119 (0.18%) developed TTS secondary to stroke. Patients with TTS were more likely to be women (79% vs 50%, p<0.001), younger (median 67 vs 70 years), present with haemorrhagic (as opposed to ischaemic stroke, p<0.001) and have a higher comorbidity burden. The mortality rate was significantly higher in those who had TTS-complicated stroke (21% vs 7.8%, p<0.001). Of patients who were discharged without having TTS during the index admission, 217 745 (6.5%) patients had 30-day unplanned readmission, among these, 214 (0.1%) were readmitted with the new diagnosis of TTS. Patients who were readmitted with TTS were more likely to be women (79% vs 50%), had higher comorbidity burden and experienced higher mortality rate during readmission compared with those without TTS (13% vs 6.5%, p=0.008).

Although rare, TTS secondary to stroke is highly fatal. Female sex, presentation with haemorrhagic stroke and pre-existing health conditions were strong factors associated with TTS-complicated stroke. Early recognition and management of TTS-complicated stroke are of paramount importance to prevent serious consequences.

The global prevalence of metabolic diseases such as obesity, diabetes, and cardiovascular diseases is closely related to overnutrition and imbalanced dietary patterns. As an important carbohydrate, starch directly affects the homeostasis of glucose and lipid metabolism due to its digestion characteristics. Resistant starch (RS) with unique anti-digestive properties and prebiotic functions has become the current hotspot in dietary nutrition research for improving glucose and lipid metabolism disorders. This review summarizes the digestive characteristics of starch and the comprehensive effects of RS and its mechanisms for ameliorating metabolic diseases. Diets with high RS content not only optimize glucose homeostasis by delaying glucose release, the undigested fractions entering the colon also drive the metabolic regulatory network of the gut microbiota-gut-brain axis by activating the AMPK/ACC pathway to reduce fat accumulation, enhancing intestinal barrier function mediated by short-chain fatty acids (SCFAs), and promoting GLP-1/PYY neural signal transduction. These insights facilitate the design of new healthy foods and inspire new strategies for optimizing dietary nutrition and regulating glucose and lipid metabolism disorders caused by high-carbohydrate diets.

Pericardial involvement is common in systemic lupus erythematosus (SLE), but distinguishing sterile immune-mediated pericarditis from septic pericarditis is difficult because clinical features overlap with sepsis, immunosuppressive effects and nonspecific serologic abnormalities. Septic pericarditis in SLE is rare yet potentially fatal and existing evidence is limited to isolated case reports.

We describe a fatal case of a patient in the fourth decade of life with newly diagnosed SLE who developed methicillin-resistant Staphylococcus aureus (MRSA) purulent pericarditis. Despite broad-spectrum antibiotics and immunosuppressive therapy for multisystem lupus activity, the patient deteriorated rapidly due to MRSA-positive pericarditis.

In parallel with this index case, we systematically searched PubMed/MEDLINE, Google Scholar and ResearchGate for case reports and series of microbiologically confirmed septic or purulent pericarditis in SLE, from inception to March 2025 and updated through November 2025. Two reviewers independently screened studies; extracted relevant clinical, microbiologic, immunologic and outcome data; and synthesised findings descriptively.

Fifteen published culture-confirmed cases plus our index case were identified (total n=16). Most patients were female (93.8%), with a mean age of 34.1 years. Staphylococcus aureus (including MRSA) and Salmonella species predominated. Dyspnoea (68.8%) was more frequent than fever (31.3%) and nearly all patients progressed to cardiac tamponade requiring urgent drainage. Survival was 93.8% when timely pericardial drainage and pathogen-directed antimicrobial therapy were achieved, while routine serological markers failed to distinguish infection from lupus flare.

Septic pericarditis in SLE is uncommon but rapidly progressive. Early echocardiography and a low threshold for diagnostic pericardiocentesis are essential to prevent fatal delay.