Search Results (256)

For nearly two decades, 12 months of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been the standard recommendation. Recent evidence suggests that abbreviated DAPT durations may reduce bleeding without compromising ischemic protection in selected patients. This review synthesizes randomized controlled trials, meta-analyses, and guideline updates published between 2023 and 2025, evaluating abbreviated DAPT strategies after ACS with percutaneous coronary intervention. Immediate aspirin withdrawal after PCI increased early stent thrombosis in NEO-MINDSET and STOPDAPT-3. One-month DAPT followed by ticagrelor monotherapy reduced bleeding without increasing ischemic events in ULTIMATE-DAPT and T-PASS. Three-month strategies demonstrated the most consistent safety profile, with TWILIGHT showing 50% bleeding reduction without increased death, myocardial infarction, or stroke (noting that TWILIGHT included 35% chronic coronary syndrome patients). Clopidogrel monotherapy after abbreviated DAPT increased myocardial infarction in STOPDAPT-2 ACS, highlighting the importance of potent P2Y12 inhibition. Meta-analyses confirmed bleeding reductions with early P2Y12 inhibitor monotherapy across broader populations, though benefits were more pronounced in East Asian cohorts. Abbreviated DAPT strategies offer personalized alternatives to standard 12-month therapy. Three-month DAPT followed by ticagrelor monotherapy represents a reasonable and evidence-supported strategy in selected patients with ACS. Risk stratification tools and individual patient factors should guide therapy duration decisions. Full article

Background/Objectives: Clopidogrel is a widely prescribed antiplatelet prodrug that requires bioactivation, primarily by the polymorphic CYP2C19 enzyme. Genetic variation in this enzyme leads to differences in active metabolite formation and has prompted the development of pharmacogenetics-guided prescribing. However, current pharmacogenetic strategies are grounded in drug metabolism knowledge derived from mass balance studies conducted in small groups of healthy volunteers. This narrow evidence base may limit the data’s applicability to real-world settings, where factors like polypharmacy or altered organ function may influence drug response. Methods: Pharmacogenetics could benefit from real-world drug metabolism and excretion studies, which we conducted for clopidogrel in 38 kidney and 16 liver transplant recipients from the TransplantLines Biobank and Cohort Study (NCT03272841), utilizing existing LC-SWATH/MS pharmacometabolomic data. Clopidogrel-associated metabolic signals were identified using xenobiotic metabolism knowledge and literature-reported pathways. Results: Across both transplant groups, 26 clopidogrel-associated features were prioritized, of which some matched previously reported urinary metabolites, had previously been observed in plasma, or represented previously unreported metabolites. Clopidogrel carboxylic acid predominated in kidney transplant recipients, whereas its glucuronide form was most abundant in liver transplant recipients. Notably, unmetabolized clopidogrel was consistently detected across all patients. Moreover, our data support a thiol desulfurization route, aligning with emerging evidence of clopidogrel’s role as a hydrogen sulfide-releasing drug. Conclusions: More (putative) clopidogrel metabolites were detected than previously reported, demonstrating the value of pharmacometabolomics in expanding our understanding of drug metabolism. This approach provides novel data that may complement pharmacogenetics research to understand clopidogrel response variability among treated patients. Full article

The ONSET–OFFSET study was a multicentre study assessing the pharmacodynamic responses to ticagrelor and clopidogrel in aspirin-treated patients with chronic coronary syndromes. Recent concerns have been raised about the study methodology, including at the single United Kingdom (UK) site in Sheffield. Here, we report data generated at this site along with additional analyses. The UK site recruited 40 out of 123 of the study participants. Platelet P2Y₁₂ receptor inhibition was assessed using light transmission aggregometry and whole-blood methodologies. Samples were obtained during the onset and offset dosing periods. Percentage inhibition of platelet aggregation (%IPA) was calculated with (pre-specified) and without (post hoc) truncation of values [0, 100]. Study conduct was monitored by an external contract research organisation. The results from the UK site were concordant with the main study findings. %IPA at 2 h after ticagrelor loading: main study 88%, UK site 91% (truncated), UK site 91% (untruncated). %IPA correlated with other measures of P2Y₁₂ inhibition (VerifyNow: p < 0.0001; VASP phosphorylation assay: p < 0.0001). One patient treated with ticagrelor had >2 h delay in the onset of platelet inhibition associated with co-administration of metformin. The primary endpoint for the offset period was also similar to the main study findings. The UK site data confirm the more rapid onset and offset of inhibitory effects and greater mean levels of platelet inhibition with ticagrelor compared with clopidogrel, regardless of the mode of %IPA data analysis. Study conduct was rigorously monitored in order to demonstrate the integrity and validity of the results. Metformin may delay the onset of action of a ticagrelor loading dose. Full article

Background and Objectives: Elderly patients frequently receive antiplatelet therapy, creating a clinical dilemma between bleeding risk and cardiovascular protection during surgery. We evaluated the association between preoperative antiplatelet therapy and postoperative bleeding and cardiovascular events using multicenter observational data. Materials and Methods: We conducted a retrospective cohort study using standardized OMOP-CDM databases from 10 tertiary hospitals. Patients aged ≥65 years undergoing surgery were classified by preoperative aspirin or clopidogrel exposure. Propensity score matching was performed within each site. Hazard ratios (HRs) were estimated using Cox regression and pooled using meta-analytic techniques. Results: A total of 1464 exposed patients and 7038 matched comparators were analyzed. Across sites, hazard ratios varied without a statistically significant pooled association. The pooled HR for postoperative events was 1.01 (95% CI 0.57–1.78, p = 0.967). Covariate balance improved substantially after matching. Conclusions: Preoperative antiplatelet therapy was not associated with a consistent increase in postoperative bleeding or cardiovascular events in elderly surgical patients. These findings support individualized perioperative management rather than routine discontinuation. Full article

Background: Managing elderly patients with simultaneous acute cardiovascular and orthopedic emergencies presents a unique challenge. While ST-elevation myocardial infarction (STEMI) requires prompt revascularization and dual antiplatelet therapy (DAPT), pertrochanteric femoral fractures usually necessitate early surgical fixation to reduce morbidity and mortality. However, the combination of these conditions complicates both standard treatment pathways. Case presentation: We present the case of an 86-year-old woman admitted after a low-energy fall, with a radiologically confirmed unstable pertrochanteric fracture of the right femur (AO/OTA 31-A2). Upon routine electrocardiogram, anterior STEMI with new-onset atrial fibrillation was diagnosed. Although asymptomatic from a cardiac perspective, bedside echocardiography revealed a severely reduced left ventricular ejection fraction of 10%. Urgent coronary angiography demonstrated a critical mid-left anterior descending lesion, successfully treated with rotational atherectomy, intravascular lithotripsy, and stent implantation. She was initiated on DAPT (aspirin + clopidogrel) and anticoagulated with low-molecular-weight heparin. Given the extremely high bleeding risk, surgical intervention for the femoral fracture was deemed unsafe. Instead, conservative management with skeletal traction (6 kg) was employed. Despite optimal supportive care and early rehabilitation, the patient experienced a complicated hospital course, including delirium, hematuria, and lower respiratory tract infection. She passed away 52 days post-admission. Conclusions: This case illustrates the complexity of clinical decision-making in geriatric patients with competing acute conditions. Current evidence on how to proceed in patients requiring both antithrombotic therapy and urgent orthopedic surgery is limited. Multidisciplinary teams must carefully weigh the risks and benefits of both surgical and conservative strategies. Further guidelines addressing such scenarios in elderly patients are urgently needed. Full article

Clopidogrel has been the most commonly used therapy for preventing secondary cardiovascular events since 1997 by inhibiting the purinergic receptor P2Y, G-protein coupled, 12 protein receptor (P2RY12). P2RY12 is critical for microglia function in the brain, where it facilitates repair processes following injury. Under normal conditions, the blood-brain barrier (BBB) prevents peripheral drugs like clopidogrel from entering the brain. However, stroke-induced BBB disruption may allow clopidogrel to interfere with neural recovery by impairing microglia activity. Recently, we demonstrated that clopidogrel worsened cognitive outcomes in young mice after stroke. In this study, we examined the effects of clopidogrel on aged mice, focusing on survival, body weight, neurovascular changes, immune response, and amyloid beta accumulation. Aged male mice underwent photothrombotic stroke (or sham surgery) and received daily clopidogrel or control treatment for 14 days. On day 15, brain tissue was analyzed. Clopidogrel treatment significantly reduced survival and body weight, decreased vessel density, increased vascular permeability, altered microglia activity, and increased amyloid beta levels in the peri-infarct region. Notably, some of these effects were not observed in young mice. These results suggest that BBB disruption in stroke mice enables clopidogrel to enter the central nervous system, where it impairs microglia-mediated restoration of BBB integrity and promotes amyloid accumulation, factors that may contribute to worsened cognitive recovery. This study raises the possibility that clopidogrel may similarly cross the BBB in older stroke patients, impacting microglial function, and emphasizes the need for further research into its mechanisms of action. Full article

Objectives: The goal of this study is to establish the incidence of high on-treatment platelet reactivity (HTPR) to aspirin and clopidogrel in patients undergoing carotid stenting and to evaluate the efficacy of ticagrelor and ticlopidine in patients with HTPR to clopidogrel. Methods: In a single institutional setting spanning eight years, every consecutive patient who underwent carotid artery stenting was incorporated into a study. Subsequently, a retrospective analysis of their platelet function was executed. Prevalence of high on-treatment reactivity to aspirin, clopidogrel, ticlopidine and ticagrelor was assessed. Platelet function testing was conducted by light transmission aggregometry and Multiplate^®. Results: A total of 216 patients were tested for antiplatelet therapy efficacy. The high on-treatment reactivity to clopidogrel was observed in 68 patients (31.4%). No patients with high on-treatment reactivity to ticagrelor or ticlopidine were observed. There was a significant reduction in platelet reactivity with ticagrelor (p < 0.000) and ticlopidine (p < 0.000) in patients with HTPR to clopidogrel. Conclusions: High on-treatment platelet reactivity to clopidogrel is common in patients undergoing carotid artery stenting. Ticagrelor is a viable alternative to overcome HTPR to clopidogrel. These findings suggest that platelet function testing can identify patients who may benefit from tailored antiplatelet therapy in reducing thromboembolic complications after carotid stenting. Full article

Background: We present our experience of carrying out endovascular therapy (EVT) of a pseudo-aneurysm of the posterior tibial artery (PTA) with an associated arteriovenous fistula (AVF). We also present results of a systematic review which was carried out to cast light on endovascular treatment modalities. Methods: A 31-year-old patient with a history of war trauma presented with pain of increasing severity in the lower leg. A CT angiogram confirmed an aneurysm of the PTA with an AVF. With a bidirectional endovascular approach, the aneurysm was occluded with coils and excluded with a Viabahn endoprosthesis. Aspirin and clopidogrel were recommended postoperatively. After 18 months of follow-up, the patient was free of symptoms, with patent endoprosthesis. Multiple databases (Scopus, Pubmed, Medline, OVID) were systematically searched using MeSH terms. The studies were scrutinized, and data on demographics, procedural details, and follow-up were collected and aggregated. Results: A total of 44 studies (56 patients) were eligible and were included. Average age was 50 (15–87 years). The most common etiology was trauma (iatrogenic 29/56 (51.7%); non-iatrogenic 15/56 (26.7%)). EVT strategies included coil embolization (n = 29), stent implantation (n = 25), and a combination of both (n = 2). Median stent diameter was 3 mm (2.5–6). The follow-up period ranged from 1 week to 60 months. Aggregated reported primary patency was 18/27 (66.6%) with no documented complications—an observation that likely reflects reporting and publication bias, rather than a true absence of adverse events. Conclusions: EVT offers a feasible and safe alternative to simple ligation or occlusion of crural aneurysms, to preserve distal flow to the foot. Dedicated stents for crural arteries are not available. Studies with long-term follow-up are lacking. Full article

High platelet reactivity (HPR) in patients with coronary artery disease receiving P2Y12 inhibitors increases ischemic risk. Chronic kidney disease (CKD) is an established contributor to HPR during clopidogrel therapy. The objective of the study was to assess whether CKD influences platelet reactivity (PR) in patients treated with clopidogrel or ticagrelor. This double-blind, double-dummy study enrolled 106 stable patients more than one year after an acute coronary syndrome, with or without CKD. Participants were matched by age and sex and randomized to clopidogrel or ticagrelor. PR was measured using the VerifyNow™ P2Y12 assay, and HPR was defined as P2Y12 reaction units (PRU) ≥ 208. Median glomerular filtration rates were 80 mL/min/1.73 m² in non-CKD patients and 41 mL/min/1.73 m² in CKD patients (p < 0.01). Ticagrelor produced similarly low PR in both groups (36 vs. 35 PRU; p = 0.61). Clopidogrel resulted in a numerically higher PR in CKD patients (209 vs. 180 PRU; p = 0.07). The magnitude of PR reduction with ticagrelor relative to clopidogrel was greater in CKD patients (p-interaction = 0.09). HPR was markedly more common with clopidogrel, particularly in CKD (difference 37%; adjusted OR 4.42; p = 0.01). In conclusion, CKD significantly impairs clopidogrel responsiveness but does not affect ticagrelor, resulting in a greater relative advantage of ticagrelor in patients with CKD. Full article

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes. Full article

Background: Restenosis after coronary stent implantation remains a major clinical challenge, especially in patients with diabetes, long lesions, or multiple stents. Standard therapy with aspirin and P2Y12 inhibitors does not reliably prevent this complication. Objectives: We reviewed experimental and clinical evidence on cilostazol, a selective phosphodiesterase-3 inhibitor, as a strategy to reduce restenosis after percutaneous coronary intervention (PCI). Methods: Preclinical and clinical studies were critically appraised, focusing on the effects of cilostazol on vascular smooth muscle and endothelial cells, platelet aggregation, lipid metabolism, and restenosis rates. Results: Experimental models show that cilostazol inhibits smooth muscle proliferation and intimal hyperplasia after arterial injury. Clinical trials demonstrate reduced restenosis after balloon angioplasty and stent implantation compared with aspirin, ticlopidine, or clopidogrel. Although approved by the FDA for intermittent claudication, cilostazol remains underused in the prevention of coronary restenosis. Conclusions: Current evidence supports cilostazol as an effective adjunctive therapy to reduce restenosis following PCI. Wider adoption and further large-scale trials are warranted to better define its role in contemporary interventional practice. Full article

Background and Clinical Significance: Statins are widely prescribed for cardiovascular risk reduction and generally demonstrate a favorable safety profile. While myalgia and elevations in liver enzymes are well-recognized adverse effects, headaches are less commonly reported and often underrecognized in clinical practice. This may result in unnecessary diagnostic evaluations, increased healthcare costs, and delayed identification of the underlying cause. Case Presentation: We describe an adult patient who developed intractable headaches that emerged after many years of statin therapy. The headaches persisted despite conventional analgesic treatment and resolved completely following discontinuation of the statin. Secondary causes were excluded, and comorbid conditions were systematically ruled out. Statin-associated headache is uncommon but clinically relevant. Proposed mechanisms include nitric-oxide-mediated vasodilation, central effects of lipophilic statins, and mitochondrial involvement. In this case, the patient was taking metoprolol succinate, lisinopril, simvastatin, clopidogrel, and tamsulosin. Except for lisinopril, none of the other comedications are strongly linked to new-onset headaches. Holding it did not resolve his headache, making simvastatin the most plausible contributor. This was confirmed by resolution of headache through its discontinuation. Because such headaches may be overlooked, clinicians should consider a statin-related cause when symptoms begin after initiation and may manage this by switching to a hydrophilic statin or using alternative lipid-lowering therapy. Conclusions: Clinicians should remain vigilant about the possibility of statin-induced headache, even in long-term users. Early recognition can prevent unnecessary diagnostic investigations, expedite symptom resolution, and support optimal management of both cardiovascular risk and treatment-related adverse effects. Full article

Feline cardiogenic arterial thromboembolism (ATE) is a severe complication of cardiac disease in cats, often causing severe clinical signs and poor prognosis. Despite its importance, standardized guidelines for prevention and treatment are lacking. This systematic review evaluated available evidence on preventive, acute, and chronic management strategies for feline cardiogenic ATE. A comprehensive search using PubMed, Scopus and Web of Science was performed, following PRISMA 2020 guidelines. Peer-reviewed studies investigating therapeutic interventions for ATE were included. Risk of bias was assessed using the SYRCLE tool. Nineteen studies involving 909 cats were included. Preventive therapy with clopidogrel and rivaroxaban improved survival. Acute multimodal treatment combining anticoagulant and antiplatelet drugs improved survival compared to monotherapy. Thrombolytic therapy showed some efficacy but had frequent severe complications. Long-term management with clopidogrel and rivaroxaban achieved the longest survival and lowest recurrence, while acetylsalicylic acid provided inconsistent benefits and more adverse effects. Eleven of the nineteen (58%) studies had high risk of bias due to small sample size and heterogeneous protocols. Current evidence supports dual therapy, particularly clopidogrel with rivaroxaban or enoxaparin, as the most effective and well-tolerated approach for prevention and treatment. Larger, standardized prospective trials are urgently needed to strengthen the evidence. Full article

Background and Objectives: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard in ST-segment elevation myocardial infarction (STEMI). Guidelines favor ticagrelor over clopidogrel, but their effect on infarct artery flow prior to percutaneous coronary intervention (PCI) remains debated. Objective was to compare the effects of aspirin + clopidogrel versus aspirin + ticagrelor pretreatment on infarct artery Thrombolysis in Myocardial Infarction (TIMI) flow in STEMI patients. Materials and Methods: This retrospective cohort study included first-time STEMI patients ≥ 18 years admitted to the Military Medical Academy, Belgrade (January 2016–January 2022), who received pretreatment with aspirin + clopidogrel or aspirin + ticagrelor and underwent PCI. TIMI flow was graded before and after PCI. Primary outcomes were pre- and post-PCI TIMI flow; secondary outcome was in-hospital mortality. Results: Of 299 STEMI patients, 174 received aspirin + ticagrelor and 125 received aspirin + clopidogrel. Pre-PCI TIMI flow was significantly higher in the ticagrelor group (p < 0.001), while post-PCI TIMI flow (p = 0.056) and in-hospital mortality (p = 0.083) did not significantly differ between groups. After exclusion of patients receiving glycoprotein IIb/IIIa inhibitors, the difference in PCI TIMI flow grade after PCI became statistically significant (p = 0.007), favoring the aspirin + ticagrelor group. In multivariate analysis, male gender, drug-eluting stent implantation, and glycoprotein IIb/IIIa inhibitor use were independently associated with reduced in-hospital mortality. Conclusions: In STEMI patients, ticagrelor-based DAPT was associated with better initial coronary flow compared to clopidogrel. However, this advantage was not evident after PCI. Male gender, drug-eluting stent implantation, and glycoprotein IIb/IIIa inhibitor use were associated with improved survival. Full article

Introduction: Femoral neck fractures in older adults are associated with appreciable short-term mortality, yet long-term survival after hip arthroplasty is incompletely characterized. We analyzed early mortality risk factors and 5- and 10-year mortality after hemi-arthroplasty or total hip arthroplasty (THA) for femoral neck fractures. Materials and Methods: In this single-center retrospective cohort, 397 consecutive patients underwent arthroplasty for femoral neck fracture in 2014 and 2015. Mean age was 83.3 years and 70.3% were women. Demographic data, Charlson Comorbidity Index, Parker Mobility Score, medication history, operative and anesthetic details, transfusion, and peri-operative complications were extracted. Survival status up to 10 years was obtained from hospital and civil registries. p-value < 0.05 was considered statistically significant. Results: A total of 397 patients were included. When categorized by age and ASA scores into low-, medium-, and high-risk groups, mortality rates increased with higher risk (p < 0.001). The mortality rate at 30 days, 90 days, 1 year, 5 years, and 10 years postoperatively was 3.5%, 7.1%, 14.1%, 48.36% and 71.03%, respectively; mean time-to-death was 3.3 years. At 30 days, mortality was higher in males, those on clopidogrel, in patients with lower mobility (lower Parker Score), higher morbidity (higher Charlson Score), NNIS score of 1, higher ASA, patient who underwent hemiarthroplasty, and patients with medical complications post-op. Additional 90-day risks were antivitamin K therapy, immunosuppressants, and continuous spinal anesthesia; 1-year risks also encompassed advanced age, prolonged hospital stay, and peri-operative transfusion. Conclusions: Arthroplasty after femoral neck fracture is associated with high mortality rate; only half of patients survive 5 years and fewer than one-third reach 10 years. Mortality rate is affected by many risk factors, both non-modifiable factors and modifiable peri-operative variables. Targeted optimization of modifiable peri-operative factors and multidisciplinary geriatric-orthopedic care may improve outcomes in this frail population. Full article