Platelets, traditionally regarded as passive mediators of hemostasis, are now recognized as pivotal regulators in the tumor microenvironment, establishing metabolic feedback loops with tumor and immune cells. Tumor-derived signals trigger platelet activation, which induces rapid metabolic reprogramming, particularly glycolysis, to support activation-dependent functions such as granule secretion, morphological changes, and aggregation. Beyond self-regulation, platelets influence the metabolic processes of adjacent cells. Through direct mitochondrial transfer, platelets reprogram tumor and immune cells, promoting oxidative phosphorylation. Additionally, platelet-derived cytokines, granules, and extracellular vesicles drive metabolic alterations in immune cells, fostering suppressive phenotypes that facilitate tumor progression. This review examines three critical aspects: (1) the distinctive metabolic features of platelets, particularly under tumor-induced activation; (2) the metabolic crosstalk between activated platelets and other cellular components; and (3) the therapeutic potential of targeting platelet metabolism to disrupt tumor-promoting networks. By elucidating platelet metabolism, this review highlights its essential role in tumor biology and its therapeutic implications.

Patients with diabetes mellitus (DM) or aspirin resistance are exposed to recurrent atherothrombotic events after acute coronary syndrome (ACS). Aspirin once-daily can allow the recovery of platelet cyclooxygenase activity before the next intake in these patients. Twice-daily administration provides more stable inhibition of platelet aggregation and may improve prognosis in these patients.

To demonstrate the superiority of twice-daily aspirin compared to once daily in reducing major adverse cardiovascular events (MACE) in patients with DM or aspirin resistance after ACS.

The ANDAMAN trial is a randomized, multicenter study including patients (aged ≥18 years) with DM or with aspirin resistance defined as: i) index event occurring under aspirin; ii) body mass index ≥ 27 kg/m2); iii) increased waist circumference (≥ 88 cm for women or ≥ 102 cm for men). The patients will be recruited in 39 centers after an ACS (with or without ST elevation) with at least one significant coronary stenosis and will be randomized before hospital discharge between twice-daily versus once daily low-dose aspirin (100 mg bid versus od). The primary composite endpoint will be the occurrence of MACE including all-cause death, myocardial infarction, stroke, urgent coronary revascularization or acute arterial thrombotic event during a follow-up of 18 months. To achieve a 20% reduction in the relative risk of MACE in the twice-daily aspirin group, a total of 2,574 patients will be included in the trial. The main secondary endpoint will be major bleeding (type 3-5 following BARC classification).

The trial will evaluate the prognostic impact of twice-daily aspirin for ACS patients with DM or aspirin resistance and may change the way aspirin is administered to these patients.

ClinicalTrials.gov Identifier: NCT02520921.

Previous studies on exercise tolerance screening in asymptomatic individuals before starting physical activity were not cost-effective due to low specificity. However, given progress in diagnosing and treating coronary artery disease (CAD), a reevaluation of this approach is justified. We aimed to examine whether stress echocardiography (SE) would be cost-effective.

The study was conducted on asymptomatic individuals with no known coronary disease. The decision tree had two arms: in one arm, the subjects underwent stress echocardiography (SE) as a screening test before starting physical activity, and in the other, they did not. The probabilities and utilities of variables in the decision tree were taken from medical literature, and the costs of treatments were obtained from the Israeli Ministry of Health Tarif (HealthCare in Israel is universal, participation in one of four official health insurance organizations is compulsory, and "supplementary insurance" is optional). A 5-year Markov model and Monte Carlo simulation with 1000 iterations were used to assess cost-effectiveness from the insurer's perspective. The variables that had the most significant impact on cost-effectiveness were the prior risk of coronary disease and the frequency of physical activity in the population under study. When cost-effectiveness assessment of SE was conducted in subjects receiving optimal medical therapy (OMT) and revascularization either transcutaneously or with bypass surgery, both groups had almost identical benefits, with a slight advantage for those who did not undergo SE. However, the cost was higher for subjects who underwent SE, and the Incremental Cost-Effectiveness Ratio (ICER) favored the No-SE group. On the other hand, when subjects only received OMT without therapeutic catheterization or bypass surgery, a cost-effectiveness assessment of SE demonstrated a lower cost and higher benefit in the group that underwent SE. In fact, SE was found to be absolutely dominant, with a negative ICER of $(-)27,644, which means that performing SE not only adds effectiveness but also saves expenses. Finally, a cost-effectiveness evaluation was conducted to compare the benefits of performing exercise tolerance testing (ETT) without stress echocardiography in subjects receiving OMT without therapeutic catheterization or bypass surgery. The results showed that the group that underwent ETT had a slightly higher benefit at a higher cost, with an ICER of $1804. This value is much lower than a WTP (willingness-to-pay) of $50,000 per year.

Performing SE as a screening test before starting physical activity in asymptomatic individuals is not cost-effective when the therapeutic options include revascularization. However, when the therapeutic policy is medical therapy without revascularization - as recommended in current guidelines - performing SE screening tests improves subjects' utility and results in financial savings. Carrying out ETT also results in improved utility that is inferior to SE as a screening test. At the same time, the ICER for ETT is still much smaller than the WTP, so performing ETT is worthwhile in cases where SE is unavailable.

Despite improvements in the secondary prevention of atherothrombosis in patients with coronary artery disease during the past decade, it is estimated that approximately 19 million people annually die from cardiovascular diseases worldwide. Atherothrombosis remains the core pathobiology of acute complications including myocardial infarction (MI), and therefore, antithrombotic therapy plays a pivotal role in the strategies for major adverse cardiovascular event (MACE) prevention. Unlike early antithrombotic management after acute coronary syndrome, less evidence is available on long-term antithrombotic therapy in patients with chronic coronary syndrome (CCS). In addition, greater recognition of the impact of bleeding complications of such therapies has led to a more complex and personalized approach to their application. The purpose of this article is to review the available evidence on long-term antithrombotic therapy in patients with CCS including those with high-risk characteristics such as prior MI or polyvascular disease.

A comprehensive literature review was performed in major databases including PubMed, Embase, and the Cochrane Library. The main focus of this narrative review was on available data from guidelines, meta-analysis, randomized controlled trials, and observational studies that assessed the efficacy and safety profile of long-term antithrombotic therapy in patients with CCS.

Several studies suggest that long-term antithrombotic therapy is effective in reducing the risk of recurrent MACEs in patients with CCS. Current clinical guidelines recommend single antiplatelet therapy with aspirin as a first-line long-term strategy for patients without indication for oral anticoagulation. However, novel approaches focused on P2Y12 inhibitor monotherapy are emerging. More intensive antithrombotic strategies including long-term dual antiplatelet therapy and dual pathway inhibition further reduce ischemic risk but at the cost of increased bleeding.

This review highlights the importance of close monitoring and regular reassessment of the risk-benefit balance of antithrombotic therapy in patients with CCS. Overall, long-term antithrombotic therapy with either single antiplatelet therapy or dual antiplatelet therapy/dual pathway inhibition is effective in reducing the risk of MACEs in patients with CCS. The choice of antithrombotic therapy should be individualized based on the patient's clinical profile, particularly for thrombohemorrhagic risk. Future research should focus on identifying the optimal antithrombotic regimen for specific subgroups of patients with prior MI particularly for those with high bleeding risk.

Over the past decade, increasing the capacity of HDL (high-density lipoprotein) cholesterol to mediate macrophage reverse cholesterol transport has been a target of interest in the treatment of cardiovascular diseases (CVDs). However, clinical studies reporting the limited efficacy of HDL or its main apolipoprotein, APOA1, in reducing cardiovascular events have emerged. Although HDL cholesterol is unlikely to play a direct causal role in CVD, its inverse, albeit modest, association with CVD risk, consistently observed in large population studies, suggests it may influence alternative pathways beyond cholesterol metabolism. Given the diverse functions of HDL and its components, it is conceivable that its impact on CVD occurs through less direct mechanisms. A potential hypothesis is that HDL modulates platelet function, a crucial player in the initiation and progression of atherothrombosis, which may contribute to its observed relationship with CVD risk. In this review, we focus on how HDL and its components, with an emphasis on APOA1, interact with platelets (and their precursors or activation products) to modulate atherothrombotic responses.

Antiplatelet and anticoagulation therapy are commonly used in the general population and sometimes in athletes experiencing cardiovascular disorders. In these cases, the treatment has to be tailored according to the individual bleeding and thrombotic risk profile, also considering the intrinsic risk of sports activities when advising athletes for eligibility for competitive sports. In athletes, it is necessary to pre-assess the individual bleeding risk, considering not only the personal bleeding risk (usually low in athletes) but also the type of sport the athlete would like to practice, with careful consideration in sports where traumatic collisions are highly likely. Additionally, non-steroidal anti-inflammatory drugs are commonly used among athletes, and antiplatelet therapy may further increase the bleeding risk. Therefore, in selected competitive athletes, the default approach for antithrombotic therapy could be personalized. This review discusses the clinical management challenges of competitive athletes under antithrombotic or antiplatelet therapy, focusing on the intrinsic risks of sports practice and the indications for sports eligibility and disqualification.

Atherosclerotic cardiovascular disease (ASCVD) continues to be a growing global health concern with ischemic heart disease and stroke as leading causes of years of life lost. While aging is a major ASCVD risk factor, recent trends show a concerning rise in its incidence among younger adults driven, in part, by increased rates of risk factors such as hypertension and diabetes. These individuals with ASCVD are at elevated risk of recurrence years following their initial event, further underscoring the need for aggressive implementation of secondary prevention strategies to reduce morbidity and mortality. This case-based review discusses evidence-based pharmacological approaches to ASCVD secondary prevention-focusing on the roles of antiplatelets, lipid lowering therapies, antihypertensive medications, and glucose lowering treatments, in practical clinical settings.

Elderly patients with coronary artery disease (CAD) are at heightened risk for ischemic and bleeding complications. This study evaluates antithrombotic therapy use and its clinical outcomes in Chinese patients aged ≥65 years with CAD and elevated ischemic risk.

This prospective cohort study enrolled patients aged ≥65 years with diagnosed CAD and ≥ 1 high ischemic risk factor from two centers. We recorded major adverse cardiovascular events (MACE)-death, nonfatal myocardial infarction, nonfatal ischemic stroke-and bleeding events over a 2-year follow-up.

Of 1005 patients (mean age 76.3 ± 7.2 years; 25.3% female), 49.0% were aged 65-75 and 51.0% were >75. Antithrombotic regimens included no therapy (1.8%), single antiplatelet therapy (SAPT, 23.0%), dual antiplatelet therapy (DAPT, 64.3%), and anticoagulation (10.9%), with 60.9% of the latter combining antiplatelet therapy. Older patients (>75 years) experienced higher MACE rates (11.5% vs 6.3%; RR: 1.825; 95% CI: 1.203-2.769; p = 0.004) and a trend towards increased bleeding (8.4% vs 6.5%; p = 0.257). Notably, all-cause and cardiovascular mortality were significantly higher in this group. Anticoagulation therapy was linked to a higher, yet non-significant, MACE rate and significantly increased bleeding risk compared to SAPT and DAPT. Multivariate analysis identified age >75, LVEF <50%, and eGFR <50 mL/min/1.73 m2 as predictors of mortality and MACE, with anticoagulation therapy increasing bleeding risk.

In elderly CAD patients, those aged >75 years exhibit higher mortality and MACE rates, with anticoagulation therapy associated with increased bleeding. Age, reduced LVEF, and renal function emerge as critical predictors of adverse outcomes.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality globally, significantly influenced by modifiable risk factors, particularly hypercholesterolemia. Despite the availability of effective lipid-reducing drugs, achieving the low-density lipoprotein cholesterol (LDL-C) target levels remains a significant challenge in clinical practice, contributing to persistently high rates of cardiovascular events. The intEgrated multidiscipliNary pathway for large-scale maNagement of dyslipidemiA in high-risk patients (ENNA) Project was designed to address the alarming rates of suboptimal lipid management in patients at high and very-high risk in the province of Enna, Sicily. This program aims to optimize LDL-C control through an integrated care model that fosters collaboration among pharmacists, general practitioners, and cardiologists, ultimately promoting a patient-centered approach to therapy. The patients who are eligible are identified using data-driven methods through prescription claims, laboratory results, and hospital discharge data, facilitated by local pharmacies. General practitioners play a crucial role as the primary care providers for initiating or optimizing lipid-reducing therapy, whereas cardiologists are involved in managing more complex cases requiring specialized intervention. The primary objective of the ENNA Project is to increase the percentage of patients at great risk in whom LDL-C targets are achieved, improving overall lipid management and therapeutic adherence.

Traumatic brain injury (TBI) patients on antiplatelet therapy face higher mortality because of impaired platelet function, which may be treated by platelet transfusion. The value of testing platelet function in this cohort remains controversial. We aimed to evaluate the relationship between platelet function assays and outcomes in TBI patients on antiplatelet therapy receiving platelet transfusions. We hypothesized that the magnitude of change in platelet assay performance following a transfusion would predict meaningful clinical outcomes.

A cohort of patients, aged 18 to 89 years, with a history of preinjury antiplatelet therapy or who required platelet transfusion, and who were deemed at risk for neurosurgical intervention, was selected from a prospective randomized controlled trial of platelet transfusion for TBI. Pre- and posttransfusion blood samples were drawn. Platelet hemostatic function assays (PHFAs) included thromboelastography with platelet mapping (TEG-PM) and VerifyNow. Logistic regression models assessed the association of temporal assay results with 30-day all-cause mortality, need for craniotomy, and initial and follow-up Rotterdam scores.

Data from 94 TBI patients (43% female) with a median age of 76 years were analyzed. The 30-day mortality rate was 14%. VerifyNow aspirin assay was able to capture increases in platelet function following a platelet transfusion in patients on aspirin (significant positive Δ = 65 aspirin response units, p < 0.001). Thromboelastography with platelet mapping parameters detected improved platelet function following transfusion, although the absolute value of changes was minimal. Thromboelastography with platelet mapping parameters predicted important clinical outcomes on logistic regression, although no significant associations with clinical outcomes were identified by the change in PHFA after transfusion or after adjusting for multiple comparisons.

Higher absolute pre- and posttransfusion values of TEG-PM were associated with decreased mortality, decreased need for neurosurgical intervention, and decreased risk of progression of hemorrhage in TBI patients taking antiplatelet agents, although neither the change in TEG-PM after transfusion nor any other PHFA value predicted outcomes.

Prognostic and Epidemiological; Level II.

Dual antiplatelet therapy is the standard of care for acute coronary syndrome, but uncertainty exists regarding the optimal regimen for patients in North America. We sought to compare the effectiveness and safety of acetylsalicylic acid (ASA) and ticagrelor or clopidogrel in patients with acute coronary syndrome from a single tertiary academic centre in Montréal, Canada.

We conducted a pragmatic, open-label, time-clustered (bimonthly between October 2018 and March 2021), randomized controlled trial. The primary effectiveness end point was a composite of all-cause mortality, nonfatal myocardial infarction, or ischemic stroke. The primary safety end point was hospital admissions for bleeding. We ascertained 12-month outcomes from the Quebec universal electronic health databases. We designed and analyzed the study within a Bayesian paradigm to supplement existing knowledge. The primary analysis was a Bayesian logistic regression model with an informed focused prior from previously randomly assigned North American patients. Robustness was evaluated with vague and other prespecified informative priors, spanning reasonable pre-existing beliefs. We defined clinically important benefits and harms as risk reductions exceeding a 10% difference.

We randomly assigned 1005 patients with acute coronary syndrome to ticagrelor (n = 450) or clopidogrel (n = 555). Major acute cardiovascular events occurred in 50 (11.1%) patients assigned to ticagrelor and 64 (11.5%) assigned to clopidogrel (relative risk [RR] 0.95, 95% credible interval 0.67-1.35, with a vague prior). The primary analysis with an informed focused prior resulted in probabilities of a clinically meaningful ticagrelor benefit (RR < 0.9), equivalence (0.9 ≤ RR ≤ 1.1) or harm (RR ≥ 1.1) of 2%, 41%, and 57%, respectively. For the safety end point, there was no consistent signal of benefit or harm with ticagrelor. Sensitivity analyses with a range of prior beliefs gave generally consistent results.

Whether we analyzed this trial with a vague or a range of reasonable informed priors, we found no strong evidence for the superiority of ticagrelor over clopidogrel in North American patients. Current guidelines favouring ticagrelor over clopidogrel might take this new evidence into future consideration.

Clinicaltrials.gov no. NCT04057300.

The effect of guideline-directed medical therapy (GDMT) on mid-term mortality in Asian patients, including Japanese patients, who have undergone endovascular therapy (EVT) for lower extremity artery disease remains still unclear. This study evaluated the effects of GDMT, defined as the combined prescription of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, on 2-year mortality in Japanese patients undergoing EVT for femoropopliteal (FP) lesions.

In this multicenter retrospective study, 1,756 registered patients were divided into 2 groups: those who received all 3 medications that comprised GDMT (full GDMT group) and those who received ≤2 medications (non-GDMT group). After propensity score matching, the baseline characteristics did not differ significantly between the 413 pairs of participants in the full GDMT and non-GDMT groups. All-cause mortality within 2 years was significantly lower in the full GDMT than non-GDMT group (14.3% vs. 20.8%; log-rank P=0.030). Mortalities from cardiovascular and cardiocerebrovascular diseases within 2 years were also significantly lower in the GDMT group (4.2% vs. 9.5% [log-rank P=0.021] and 4.2% vs. 10.5% [log-rank P=0.007], respectively).

In Japanese patients undergoing EVT for FP lesions, GDMT may improve all-cause, cardiovascular, and cardiocerebrovascular mortality within 2 years.

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis. It is often associated with coronary and/or cerebral vascular involvement, leading to a higher risk of cardiovascular and cerebrovascular events, among which myocardial infarction, stroke, and death. Cardiovascular prevention has proven effective in reducing the progression of the disease and early diagnosis leads to more rapid initiation of medical therapy. However, revascularization of the diseased segment represents the only solution in the manifest and symptomatic forms of the disease.

Surgical treatment has historically represented the first treatment of PAD, which consists in the creation of bypasses excluding the obstructed segment. Nowadays, endovascular treatment represents in many cases the first line of intervention. Drug-coated balloons are a cornerstone solution for the treatment of peripheral lesions and are supported by multiple trials demonstrating their efficacy and safety.

New devices, such as sirolimus-eluting balloons, and also new eluting technologies will further improve the efficacy and the results of peripheral angioplasty. In the next years, we will experience the routinary use of new techniques currently under study. In this review, we will discuss the role of drug-coated balloons in the treatment of PAD.

Arachidonic acid (AA) metabolism is a critical regulator of platelet activation. The cytochrome P450 (CYP450) pathway represents a key metabolic route for AA, yet the precise roles of CYP450 enzymes and their primary product, 20-hydroxyeicosatetraenoic acid (20-HETE), in platelet activation and thrombosis remain incompletely elucidated.

We assessed the impact of aspirin on AA-induced platelet aggregation in human platelets. We further explored the influence of 20-HETE on platelet aggregation, granule secretion, and integrin activation. To elucidate the underlying mechanisms of 20-HETE action, we employed the antagonist 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) and G protein-coupled receptor 75 (GPR75) knockout mice. Additionally, we evaluated the antiplatelet potential of the CYP450 inhibitor 17-octadecynoic acid (17-ODYA).

Aspirin suppressed platelet aggregation induced by low dose of AA and has no effect on high dose AA-induced aggregation.20-HETE indirectly induced platelet aggregation, granule release, and integrin αIIbβ3 activation in a concentration-dependent manner, independent of GPR75. The effects of 20-HETE were mediated through Gαq-coupled GPCRs. The CYP450 inhibitor 17-ODYA potently suppressed platelet activation and thrombus formation.

Thromboxane A2 (TXA2) is not indispensable for AA induced platelet activation. Moreover, 20-HETE has been identified as a potent platelet activator that acts through Gαq-coupled GPCRs. Its effects are mediated by downstream metabolites rather than direct interaction with GPR75.

Currently, there is not sufficient data regarding the prevalence of resistance or inadequate platelet function inhibition with the use of antiplatelet therapy in patients with noncardioembolic stroke. This study was designed to evaluate the prevalence of antiplatelet inactivity to aspirin and clopidogrel in the setting of chronic use and presentation with primary or recurrent stroke.

Patients who were taking aspirin, clopidogrel, or both at the time of presentation for stroke were selected in this study. Those with confirmed stroke on MRI or clinically determined TIA and age > 18 years were included. A standard laboratory test, VerifyNow aspirin or P2Y12 assay, was utilized to assess the responsiveness to the platelet inhibitors. A total of 158 patients were identified, 52 presenting with primary stroke and 106 with recurrent stroke. Data were analyzed using chi-squared or Fisher's exact as well as t-test analysis.

Of the primary stroke population, 4% of patients demonstrated resistance to aspirin and 30% to clopidogrel. Of the patients presenting with recurrent stroke, 13% demonstrated resistance to aspirin and 38% to clopidogrel. The data also suggest increased resistance to aspirin and clopidogrel in Caucasians compared to minorities, with 11% versus 8% in regard to aspirin and 33% versus 17% to clopidogrel. Additionally, this study demonstrated 17% resistance to aspirin in males compared to 4% in females and 13% in males compared to 36% in females, respectively, regarding resistance to clopidogrel. No difference in inactivity to either aspirin or clopidogrel was detected between patients with stroke mechanisms of small or large vessel disease.

The present result demonstrated that a sizeable portion of the population has inefficacious activity in the setting of specific antiplatelet agents. Additionally, sex and ethnicity differences in responsiveness to aspirin or clopidogrel have been noted. Determining a patient's response to medications could provide opportunities to individualize treatment and better prevent future strokes. Further studies of a larger scale are indeed needed to apply this information to pursue individualized treatment.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12inhibitor, has been the principal antiplatelet therapy after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) and chronic coronary disease. Particularly in patients with ACS, which presents a higher ischemic risk than chronic coronary artery disease, DAPT for up to 12 months is the recommended standard treatment. However, to decrease bleeding events related to the potency of P2Y12inhibitors and a prolonged duration of DAPT, recent studies have suggested P2Y12inhibitor monotherapy after short-term DAPT (1-3 months), which decreased the bleeding risk without an increased ischemic risk. In this article, we discuss the evidence related to the efficacy of a P2Y12inhibitor as single-antiplatelet therapy after short-term DAPT compared with standard DAPT, with a focus on patients with ACS treated with DES.

The link between cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD) is well-established at both the epidemiological and pathophysiological levels. Among the common pathophysiological mechanisms involved in the development and progression of both diseases, oxidative stress and inflammation, insulin resistance, lipid metabolism deterioration, hepatokines, and gut dysbiosis along with genetic factors have been recognized to play a pivotal role. Pharmacologic interventions with drugs targeting common modifiable cardiometabolic risk factors, such as T2DM, dyslipidemia, and hypertension, are a reasonable strategy to prevent CVD development and progression of MASLD. Recently, a novel drug for metabolic dysfunction-associated steatohepatitis (MASH), resmetirom, has shown positive effects regarding CVD risk, opening new opportunities for the therapeutic approach of MASLD and CVD. This review provides current knowledge on the epidemiologic association of MASLD to CVD morbidity and mortality and enlightens the possible underlying pathophysiologic mechanisms linking MASLD with CVD. The role of cardiometabolic drugs such as anti-hypertensive drugs, hypolipidemic agents, glucose-lowering medications, acetylsalicylic acid, and the thyroid hormone receptor-beta agonist in the progression of MASLD is also discussed. Metformin failed to prove beneficial effects in MASLD progression. Studies on the administration of thiazolinediones in MASLD suggest effectiveness in improving steatosis, steatohepatitis, and fibrosis, while newer categories of glucose-lowering agents such as GLP-1Ra and SGLT-2i are currently being tested for their efficacy across the whole spectrum of MASLD. Statins alone or in combination with ezetimibe have yielded promising results. The conduction of long-duration, large, high-quality, randomized-controlled trials aiming to assess by biopsy the efficacy of cardiometabolic drugs to reverse MASLD progression is of great importance.

Antithrombotic management in patients with chronic coronary syndrome and previous stent implantation who require long-term oral anticoagulation is highly challenging in daily practice, especially in those at high residual risk of coronary and vascular events. Dual therapy with oral anticoagulation and aspirin may lead to a higher risk of bleeding, whereas stopping aspirin in high-risk patients with coronary artery disease after percutaneous coronary intervention may lead to recurrent ischaemic events.

To assess the optimal antithrombotic regimen that should be pursued long term (often lifelong) in these patients.

The AQUATIC study is a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicentre study conducted in patients with chronic coronary syndrome at high risk of ischaemic events (i.e., stent implantation [> 6 months before inclusion] in a context of previous acute coronary syndrome and/or with high-risk features of ischaemic event recurrences) and requiring long-term oral anticoagulation. For superiority, we ensure 80% power at level α=0.05 to detect a 25% reduction in hazard in the experimental group relative to the control group. Overall, 2000 patients will be randomized in a 1:1 ratio to receive either oral anticoagulation and aspirin or oral anticoagulation and placebo. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization and acute limb ischaemia. Major bleeding according to the International Society on Thrombosis and Haemostasis definition is a secondary safety endpoint that will be assessed as a priority.

The AQUATIC trial will test the efficacy and safety of adding aspirin to long-term oral anticoagulation in patients with chronic coronary syndrome and previous coronary stenting who are at high residual risk of recurrent ischaemic events and require oral anticoagulation.

The hemostatic function of platelets is complementary to blood coagulation. However, traditional platelet function tests have primarily focused on measuring platelet aggregation, reducing their clinical effectiveness for antiplatelet drug monitoring. To address this limitation, we propose a new test principle that evaluates platelet function and the effects of antiplatelet drugs through blood coagulation reactions. This principle was validated in model experimental systems using blood samples from healthy volunteers (n = 11), where antiplatelet drugs such as aspirin, prostaglandin E1, or ticagrelor were added to the blood samples. Ticagrelor was tested at four concentration levels, covering the expected therapeutic range. We found that the complementary function of platelets can be assessed by monitoring the 1 MHz dielectric permittivity during the blood coagulation process, particularly the peak value. When reagents such as agonists (arachidonic acid, collagen, or adenosine diphosphate ADP) and calcium were mixed into the citrated blood with turbulence by pipetting, platelets became activated and aggregated before thrombin generation, resulting in a "consumed" state of platelets. Consequently, the contribution to the permittivity peak was minimal. By contrast, when blood spiked with antiplatelet drugs was tested, agonist-induced platelet aggregation was inhibited during the initial stage of the measurement. However, after thrombin generation, platelets were activated through the thrombin receptor. These activated platelets interacted with fibrin, thereby affecting the permittivity peak. The results of this validation process with Student's t-tests confirm the fundamental operating principle of the proposed platelet function assay, thereby contributing to antiplatelet therapy monitoring.

Advances in pharmacotherapy for coronary thrombosis treatment and prevention have transformed the clinical outcomes of patients with coronary artery disease but increased the complexity of therapeutic decision-making. Improvements in percutaneous coronary intervention techniques and stent design have reduced the incidence of thrombotic complications, which consequently has increased the challenge of adequately powering clinical trials of novel antithrombotic strategies for efficacy outcomes. Knowledge of the pathophysiology of coronary thrombosis and the characteristics of antithrombotic drugs can help with therapeutic decisions.

This review covers the pathophysiology of coronary thrombosis and the mechanisms of action of drugs developed for its treatment, provides an overview of the key issues in decision-making, and highlights key areas for further work in order to guide clinicians on how to individualize risk management and address gaps in the evidence base.

Individualization of antithrombotic therapy regimens has become a vital part of optimizing risk management in people with coronary thrombosis. A critical appraisal of the strengths and limitations of available drugs and the evidence supporting the use of different antithrombotic combinations is intended to provide direction to clinicians and point the way toward further improvements in pharmacotherapy for coronary thrombosis treatment and prevention.

Antiplatelet drugs are a cornerstone in managing atherosclerotic vascular disease (ASVD). However, their interactions with other medications present significant challenges to treatment efficacy and safety. Patients with ASVD often require multiple treatment regimens due to complex comorbidities, which increases the risk of drug-drug interactions (DDIs). These interactions can lead to drug resistance, reduced therapeutic outcomes, or adverse effects. A thorough understanding of DDIs is crucial for optimizing patient care.

This review aims to explore the clinical significance. mechanisms, and implications of DDIs in antiplatelet therapy Additionally, it seeks to identify future research directions to advance personalized treatment strategies and improve therapeutic outcomes.

A systematic literature review was conducted using key databases, focusing on clinical studies, mechanistic research, and guidelines related to antiplatelet therapy and DDIs. Findings were analyzed to identify common interaction patterns, associated risks, and management strategies.

The review identifies common DDIs involving antiplatelet drugs, particularly with anticoagulants, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors. These interactions primarily occur through pharmacokinetic mechanisms, such as alterations in drug metabolism via cytochrome P450 enzymes, and pharmacodynamic mechanisms, including synergistic or antagonistic effects on platelet inhibition. Clinically, DDIs can increase bleeding risk, reduce antiplatelet efficacy, and contribute to adverse cardiovascular outcomes. Strategies to mitigate these risks include individualized drug selection, dose adjustments, genetic testing, and therapeutic drug monitoring.

Effective management of DDIs in antiplatelet therapy is essential to improve clinical outcomes. A patient-specific approach, considering comorbidities, genetic predispositions, and concurrent medications, is crucial. The review categorizes DDIs based on clinical settings and underscores the need for further research on predictive biomarkers, pharmacogenomics, and advanced monitoring techniques.

DDIs significantly impact the effectiveness and safety of antiplatelet therapy, necessitating a comprehensive understanding of their mechanisms and clinical implications. Future research should focus on developing personalized treatment approaches, integrating genetic testing, and optimizing pharmacological monitoring to minimize risks and improve therapeutic outcomes. This review provides a foundation for advancing clinical practice and enhancing the management of patients with ASVD.

Stroke is the leading cause of disability globally, with antiplatelet therapy being crucial for secondary prevention but also increasing bleeding risks. This requires careful dosage adjustments to balance thrombosis and bleeding risks.

This study compared the efficacy and safety of low-dose versus standard-dose antiplatelet therapy in stroke patients.

We conducted a comprehensive search across multiple databases, including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, CNKI, and the Wanfang Medical Database, up to March 2024. Only randomized controlled trials assessing low-dose antiplatelet therapy in stroke patients were considered. The Cochrane Risk of Bias Tool (RoB 2) was used for quality. Performed meta-analysis using Stata 15.0, with relative risk (RR) and 95% confidence interval (CI) as effect estimates.

Ten studies involving 7,703 Asia participants, mainly from China and Japan, were analyzed. The meta-analysis revealed that low-dose reduces the risk of bleeding (RR 0.51; 95% CI 0.27, 0.98) compared to standard dose, with similar risks for stroke (RR 1.04; 95% CI 0.69, 1.55), myocardial infarction (MI) (RR 1.91; 95% CI 0.88, 4.12), all-cause death (ACD) (RR 1.17; 95% CI 0.38, 3.62), and major bleeding (RR 0.74; 95% CI 0.16, 3.30). Subgroup analysis revealed that compared to standard-dose clopidogrel, low-dose clopidogrel increased the risk of MI. Notably, this increased risk was observed specifically within the Chinese population but not in the Japanese population. Low-dose clopidogrel and low-dose prasugrel reduce the risk of bleeding compared to standard-dose clopidogrel, but there is no statistically significant difference. Low-dose aspirin significantly reduces the risk of bleeding compared to standard-dose aspirin.

In patients with stroke in Asia, low-dose antiplatelet therapy significantly reduces the risk of bleeding compared to standard doses, with consistent risks of stroke, MI, ACD, major bleeding, and discontinuation due to bleeding.

Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the "less traditional" designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.

Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa.

We conducted a modeling study to simulate hypertension and CVD across 3,000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated 2 policies compared to current hypertension treatment: (1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy); and (2) CCC plus population-level hypertension screening of adults ≥40 years of age by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Among adults 45 to 64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1% to 7%) to 14% (6% to 26%); additional CHW screening would improve control to 44% (35% to 54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3% to 17%), strokes by 13% (5% to 23%), and CVD mortality by 9% (3% to 15%). CCC plus CHW screening would reduce IHD by 28% (19% to 36%), strokes by 36% (25% to 47%), and CVD mortality by 25% (17% to 34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC.

Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa.

Optimal medical therapy (OMT) for peripheral artery disease (PAD) is associated with decreased major amputation and mortality. OMT has several components, including antiplatelet and high-intensity statin therapy, blood pressure control, etc. While there are disparities in receipt of OMT among PAD patients, it is unknown if patients from disadvantaged neighborhoods, measured by the area deprivation index (ADI), are less likely to be on OMT.

We performed a retrospective review of patients that underwent major lower extremity amputation between 2015 and 2019 at 2 large academic healthcare systems. Primary exposure was high ADI, defined as ADI ≥60th percentile, and secondary exposure was non-Hispanic Black (NHB) race. For each analysis, the primary outcome of interest was receipt of OMT, defined here as at least one antiplatelet agent and a high-intensity statin. The exposure outcome relationship was assessed using multivariable logistic regression.

Among 354 patients with median age of 66 (interquartile range [IQR] 58-74), 267 (75.4%) were male, 219 (61.9%) identified as NHB and 116 (32.8%) as non-Hispanic White (NHW). Overall, 91 (25.7%) patients were on OMT at time of amputation despite 57.3% of the cohort being established with a vascular surgeon. Compared to those with low ADI, the category high ADI had a higher proportion of NHB patients (48.1% vs 70.3%, P = 0.001) and patients were more often hospitalized at the University-affiliated facilities (47.4% vs 63.0%, P = 0.004). High ADI was not associated with receipt of OMT prior to major amputation (adjusted odds ratio [aOR] 0.72, 95% confidence interval [CI] 0.42-1.24). In secondary analysis, NHB race was not associated with receipt of OMT. Stratification by facility type (Veterans Affairs and University-affiliated facilities) also showed no association between high ADI or race and receipt of OMT.

Neighborhood economic well-being is not associated with receipt of OMT prior to major amputation. While the absence of socioeconomic disparities is notable, the proportion of patients on OMT is suboptimal. Care processes should be critically evaluated and quality measures potentially created to improve the rate of receipt of OMT among patients at risk for amputation.

The association between aspirin and hepatocellular carcinoma (HCC) has been reported to prevent carcinogenesis caused by hepatitis B or C virus infection. The objective of this study was to investigate the prognostic impact of aspirin in patients who underwent liver resection for HCC.

Data for 1032 patients who underwent primary resection for HCC between 2000 and 2019 were reviewed. There were 87 patients (8.4%) who took aspirin (aspirin group) and 945 (91.6%) who did not (non-aspirin group). Short-term outcomes, recurrence-free survival (RFS), and overall survival (OS) were compared between two groups in the matched cohort using propensity-score matching.

The median patient follow-up was 42.6 months (95% confidence interval 3.12-136.8 months). There was no significant difference in short-term outcomes, including bleeding events. RFS and OS after liver resection in the aspirin group were significantly better than those in the non-aspirin group in the unmatched cohort [5-year RFS rate: 50.3% vs 31.4%, hazard ratio (HR) 0.55, P = 0.0002; 5-year OS rate: 82.9% vs 70.2%, HR 0.46, P = 0.002]. In the matched cohort, RFS and OS after liver resection in the aspirin group were also significantly better than those in the non-aspirin group (5-year RFS rate: 50.3% vs 32.0%, HR 0.60, P = 0.003; 5-year OS rate: 82.9% vs 74.6%, HR 0.56, P = 0.03).

Use of aspirin was associated with better prognosis for patients who underwent primary resection for HCC.

Aspirin treatment is recommended as a secondary prevention strategy and could be a potential primary prevention strategy for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). However, aspirin resistance is notably common among diabetic patients, compromising the efficacy of aspirin treatment. Hence, our study sought to assess the clinical predictors of aspirin resistance (AR) in T2DM patients.

We conducted a systematic search of three major medical databases (PubMed, Embase, and Cochrane Library) to identify relevant articles up to September 17, 2024. Details of publications and investigated parameters were extracted from the selected studies. The meta package in the R language software was utilized to synthesize the evidence concerning clinical predictors of AR. We applied either a fixed- or random effects model based on the heterogeneity observed among the included studies. The pooled results were visually displayed using forest plots.

In total, 10 publications were finally included in our study (n = 2113 patients). AR was predominantly linked to specific laboratory parameters, particularly those indicative of heightened insulin resistance and inadequate lipid management. Specifically, the laboratory parameters associated with AR included fasting glucose level (mean difference (MD) = 8.21; 95% confidence interval (CI) = 2.55 to 13.88), glycated hemoglobin (MD = 0.22; 95% CI = 0.06 to 0.38), high-density lipoprotein (HDL) level (MD = -2.02; 95% CI = -3.62 to -0.42), low-density lipoprotein (LDL) level (MD = 7.00; 95% CI = 2.87 to 11.13), total cholesterol level (MD = 9.52; 95% CI = 4.37 to 14.67), and triglyceride levels (MD = 12.51; 95% CI = 3.47 to 21.55).

Markers associated with dyslipidemia and blood glucose levels are robust indicators of AR in individuals with T2DM. These findings imply that assessing lipid and glucose regulation could enhance the development of personalized preventive approaches for vascular complications linked to diabetes.

CRD42023388170, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=388170.

Objectives: Evidence for antithrombotic therapy after endovascular therapy (EVT) is limited. Methods: This retrospective, multicenter, observational study enrolled 732 consecutive patients with lower extremity artery disease who underwent EVT between January 2018 and December 2019. Overall, 570 patients who received single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) were selected and divided into the SAPT (n = 189) and DAPT (n = 381) groups. The primary outcome was bleeding events at 24 months. The secondary outcomes were bleeding events at 30 days and 24 months after 30 days, ischemic events, and all-cause death at 24 months. Bleeding and ischemic events at 24 months were investigated in subgroups. Results: A propensity score matching yielded 164 patients in both groups. There were no significant differences in bleeding events between the SAPT and DAPT groups (14.2% and 11.3% at 24 months, p = 0.775; 2.5% and 6.1% at 30 days, p = 0.106; 11.7% and 6.7% at 24 months after 30 days, p = 0.162). Additionally, there was no significant difference in ischemic events at 24 months between the two groups (32.7% and 30.6%, p = 0.625). Bleeding and ischemic events at 24 months were similar between subgroups. Conclusions: No significant differences in bleeding or ischemic events between SAPT and DAPT were observed.

Acute myocardial infarction (AMI) remains a significant cause of global mortality, exacerbated by ischemia-reperfusion (IR) injury. Myocardial cell pyroptosis has emerged as a critical pathway influencing IR injury severity.

We aimed to investigate the cardioprotective effects of aerobic exercise on IR injury by examining the modulation of IGFBP2 and its impact on GSDME-dependent myocardial cell pyroptosis. Mechanistic pathways were explored using western blot analysis, ELISA, immunofluorescence, and echocardiography.

Our findings demonstrate that aerobic exercise leads to increased circulating levels of IGFBP2, which effectively suppresses GSDME-dependent myocardial cell pyroptosis. This regulation occurs via the AKT-GSK3β signaling pathway, involving VDAC1 phosphorylation, thereby enhancing mitochondrial function and reducing oxidative stress.

In conclusion, our study highlights the role of IGFBP2 in mitigating GSDME-dependent pyroptosis as a mechanism through which aerobic exercise exerts cardioprotective effects against IR injury. These insights suggest potential therapeutic targets for managing acute myocardial infarction.

The adverse effects of aspirin are dose-dependent, and there is controversy surrounding the use of low-dose (LD) aspirin to prevent venous thromboembolism (VTE) following total joint arthroplasty (TJA). This meta-analysis sought to compare the efficacy and complication rate of low-dose (162 mg per day) versus high-dose (HD, 650 mg per day) aspirin after TJA surgery.

In four main databases, we searched from inception until September 2024 for articles comparing the rate of VTE following TJA(TKA/THA) using only aspirin chemoprophylaxis with different dosages. We meta-analyzed and compared the VTE and complication rates of LD aspirin (162 mg per day) with HD aspirin (650 mg per day) and presented our results as odds ratio (ORs) in forest plot diagrams.

There were 14 eligible studies, comprising 43,518 patients in the LD group and 62,645 patients in the HD group. DVT (OR: 1.37, CI: 0.93-2.02, P = 0.11) and PE (OR: 1.86, CI: 0.73-4.72, P = 0.19) rates were similar between the groups. However, taking VTE as the total number of cases with DVT or PE, the incidence was significantly higher in the HD group than in the LD group (OR:1.53, CI: 1.17-2.00, P = 0.002). HD also had a significantly higher rate of PJI (OR:2.68 CI:1.5-4.6 P = 0.001), but gastrointestinal bleeding (GIB) was similar between the two groups (OR: 0.97, CI: 0.42-2.22, P = 0.95).

The findings suggest that LD aspirin may be a viable option for VTE chemoprophylaxis following TJA, potentially offering comparable efficacy with a lower risk of PJI compared to HD aspirin regimens.

Therapeutic Level II.

Cardiovascular disease (CVD) and diabetes mellitus are prominent public health concerns in Saudi Arabia owing to their increasingly high prevalence and burden. Based on this, the Saudi Heart Association (SHA) set out to develop an official position statement on CVD and diabetes mellitus, with a focus on the prevention and management of these conditions and relevant special populations in the context of Saudi Arabia.

A multidisciplinary panel of experts met under the auspices of the SHA in a series of meetings to review and discuss available evidence on the prevention and management of comorbid CVD and diabetes mellitus. Specialized subcommittees reviewed the data and offered context-specific recommendations (taking into account Saudi population characteristics, local healthcare system, available resources and medical expertise), which were later approved by the full expert panel.

The prevalence of diabetes mellitus and CVD is alarming in the Saudi Arabian population. Diabetes mellitus and CVD are interconnected on several levels, including cellular and molecular events as well as epigenetic and genetic mechanisms. Screening for CVD is a priority for patients with diabetes and concomitant risk factors. The expert panel also recommends aggressive management of high blood pressure and dyslipidemia in addition to lifestyle changes and achieving glycemic targets for the prevention of CVD in patients with diabetes. Some glucose-lowering drug classes, namely SGLT2-inhibitors and GLP-1 receptor agonists, offer significant benefits on the level of cardiovascular risk reduction and are thus a powerful addition to the clinical management armamentarium in CVD and diabetes. Special consideration is also advised for patient populations with distinct clinical presentation and needs, such as coronary artery disease, heart failure, and chronic kidney disease, among others.

Background/Objectives: Despite the widespread use of oral anticoagulants (OACs), acute ischemic stroke (AIS) remains a significant risk for patients with atrial fibrillation (AF). The real-world effectiveness of OACs in preventing recurrent strokes, particularly following an initial stroke of cardioembolic (CE) origin, continues to be a major challenge for clinicians managing AF patients. This study evaluated the efficacy of OACs in secondary stroke prevention and investigated the influence of anticoagulation type and quality on recurrence risk. Methods: We analyzed data from 128 AF patients in the prospective Transzlációs Idegtudományi Nemzeti Laboratórium (TINL) STROKE-registry, admitted with CE stroke between February 2023 and September 2024. Patients were categorized by anticoagulation status at admission (OAC-users, n = 89; anticoagulation-naïve, n = 39). Recurrence rates were assessed using logistic regression models, adjusted for age, sex, hypertension, diabetes, and pre-stroke disability. Subgroup analyses explored the effects of anticoagulation type and quality. Results: Recurrence rates were similar between the OAC-treated and anticoagulation-naïve patients after adjusting for confounders (19.10% vs. 17.95%, p = 0.870). Among the anticoagulated patients, neither anticoagulation type nor quality alone significantly influenced the recurrence risk. However, their interaction was statistically significant (p = 0.049), suggesting that the effectiveness of anticoagulation in preventing strokes is strongly affected by treatment quality. Conclusions: Although OACs are a cornerstone of stroke prevention in patients with AF, their efficacy in reducing recurrence depends on optimal management. These findings highlight that adequate anticoagulation, not just its use, is critical to minimize recurrence risk. To effectively prevent strokes in high-risk AF patients, future strategies must focus on standardized protocols, tailored monitoring, and individualized dosing regimens.

To demonstrate the therapeutic similarity of CT-P42 compared with reference aflibercept (Eylea) in adult patients with diabetic macular edema (DME).

Randomized, active-controlled, double-masked, phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus with DME involving the center of the macula.

Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 ml) by intravitreal injection every 4 weeks (5 doses), then every 8 weeks (4 doses), in the main study period. Results up to week 24 are reported herein.

The primary end point was mean change from baseline at week 8 in best-corrected visual acuity (BCVA) using the ETDRS chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the 2-sided 95% confidence interval (CI) (global assumptions) and 2-sided 90% CI (United States Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set.

Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). Best-corrected visual acuity improved from baseline to week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the predefined equivalence margin of ±3 letters (95% CI, -0.73 to 1.88 [global]; 90% CI, -0.52 to 1.67 [FDA]). Through week 24, other efficacy results for the 2 groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing ≥1 treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups.

This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 ml) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.