Search Results (36)

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

Background and Objectives: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard care for acute coronary syndrome (ACS). Although ticagrelor showed superiority over clopidogrel in pivotal trials, patients with advanced chronic kidney disease (CKD) or on dialysis were underrepresented and results in Asian populations have been inconsistent. Materials and Methods: We conducted a retrospective cohort study using the Taiwan Society of Cardiology Acute Coronary Syndrome-Diabetes Mellitus (TSOC ACS-DM) registry between 1 October 2013, and 30 September 2016. Eligible patients had type 2 diabetes mellitus and ACS with stage III–V CKD or were on dialysis at index hospitalization and were discharged on aspirin plus either ticagrelor or clopidogrel. The primary endpoint was a composite of cardiovascular (CV) death, CV-related readmission, and repeated revascularization. Cumulative incidence functions were compared using expectation maximization (EM) weighting and propensity score adjustment. Results: After exclusions, 451 patients were analyzed (ticagrelor n = 116; clopidogrel n = 335). Ticagrelor associated with higher myocardial infarction (HR 1.59, 95% CI 1.12–2.28, p = 0.010), CV-related readmission (HR 1.72, 95% CI 1.12–2.65, p = 0.014), repeated revascularization (HR 2.24, 95% CI 1.36–3.68, p = 0.002), and the composite endpoint (HR 1.63, 95% CI 1.06–2.48, p = 0.024) at 2 years. Conclusions: Among real-world Taiwanese patients with type 2 diabetes mellitus, ACS, and CKD, ticagrelor use was linked to increased risks of cardiovascular events compared to clopidogrel. However, these relationships might be affected by potential confounding factors. Randomized controlled trials are necessary to establish the best antiplatelet strategy for this high-risk group. Full article

Background and Objectives: The benefits of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among high-risk patients with diabetes are controversial owing to bleeding risk. Current guidelines recommend the use of aspirin in high-risk patients with diabetes; however, the supporting evidence is inconsistent, primarily due to an increased risk of gastrointestinal (GI) bleeding. Given these concerns, it is important to explore alternative antiplatelet strategies. Clopidogrel, a widely used P2Y12 inhibitor, has been suggested to cause fewer GI bleeding events than aspirin. Accordingly, we aimed to compare the efficacy and bleeding risk of clopidogrel versus aspirin in high- and very high-risk populations with diabetes without prior ASCVD using the Korean National Health Insurance Service data. Materials and Methods: Propensity score-matching was performed to reduce baseline imbalances. The primary endpoint was net adverse clinical events (NACEs), defined as a composite of all-cause death, myocardial infarction (MI), stroke, intracranial hemorrhage (ICH), and gastrointestinal GI bleeding. Secondary endpoints included efficacy (composite of all-cause death, MI, and stroke) and bleeding outcomes (GI bleeding and ICH). Results: Among 10,453 patients (9550 on aspirin and 903 on clopidogrel), 902 matched pairs were analyzed. Clopidogrel showed no significant difference compared with aspirin in NACE incidence (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.79–1.19), efficacy endpoints (HR: 1.02; 95% CI: 0.82–1.26), or individual outcomes (MI, stroke, all-cause death). Clopidogrel demonstrated a trend towards lower GI bleeding (HR: 0.48; 95% CI: 0.23–1.01), although not significant. In subgroup analysis, male patients on clopidogrel had significantly lower NACE risk than those on aspirin (HR: 0.73; 95% CI: 0.54–0.99). Conclusions: These findings suggest that clopidogrel may be considered a preferable alternative to aspirin for primary prevention in high-risk male patients with diabetes, particularly those with an elevated risk for gastrointestinal bleeding, guiding personalized antiplatelet therapy choices in clinical practice. Full article

Background/Objectives: Patients suffering from fractures are often treated with clopidogrel during the phase of bone healing due to multiple comorbidities. Studies indicate that clopidogrel suppresses osteoblast proliferation and the formation of trabecular bone. However, it is unknown whether clopidogrel also affects fracture healing under ischemic conditions, as they may occur in multimorbid patients. Methods: To test this in the present study, a murine ischemia model was performed in CD-1 mice by ligating the right deep femoral artery to induce mild ischemia of the right lower limb. A closed fracture of the femur was then stabilized by inserting an intramedullary lag screw. The animals received either 3 mg/kg body weight clopidogrel daily per os or vehicle (control). Bone healing was assessed by biomechanical, radiological, histomorphometrical and Western blot analyses 2 and 5 weeks postoperatively. Results: The fractured femurs in the clopidogrel group exhibited no increase in biomechanical stiffness throughout the observation period in contrast to controls. While the radiological analysis showed no differences between both groups, histomorphometric analyses demonstrated a significantly reduced bridging score, less bone and more connective tissue within the callus of clopidogrel-treated animals. Western blot analyses revealed a significantly reduced expression of the osteogenic marker bone morphogenetic protein (BMP)-4 and an increased expression of the blood vessel marker CD31. Conclusions: These results show that clopidogrel may impair fracture healing under challenging ischemic conditions, which is associated with a shift in angiogenic and osteogenic expression markers in the callus tissue. Therefore, clopidogrel treatment may not be recommended in fracture patients with tissue ischemia. Full article

Background: Ischemic stroke (IS), a major cerebrovascular disease, is associated with high disability and mortality rates. Acute kidney injury (AKI) often complicates IS and increases in-hospital mortality. While antiplatelet agents are commonly used for IS treatment, their effectiveness in IS patients with AKI is unclear. Methods: This study, using data from the MIMIC-IV database, divided patients into non-combination (clopidogrel or ticagrelor alone) and combination (with aspirin) groups. The primary outcome was 28-day mortality, with secondary outcomes including 90-day, 1-year, and in-hospital mortality. Multivariable Cox and logistic regression models were used to analyze the relationship between antiplatelet regimens and mortality. Subgroup analyses and interaction tests were conducted. Results: Results showed the combination group had lower 28-day, 90-day, 1-year, and in-hospital mortality risks than the non-combination group (all p < 0.001). Subgroup analysis revealed an interaction effect by AKI stage, with combination therapy not significantly reducing mortality in severe AKI (stages 2 and 3, p = 0.743, p = 0.244). Conclusions: This study demonstrates that combination antiplatelet therapy significantly reduces 28-day, 90-day, 1-year, and in-hospital mortality risks of IS patients with AKI, suggesting its potential benefits in improving both short- and long-term clinical outcomes. However, this does not apply to patients with severe AKI, indicating heterogeneous survival benefits of combination therapy across AKI severity. Clinical decision-making should incorporate AKI stage stratification to evaluate the applicability of combination antiplatelet therapy. Further research is needed to explore the impact of AKI staging on antiplatelet therapy in IS patients. Full article

Background/Objectives: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis or obstetric complications and the laboratory detection of antiphospholipid antibodies. Although vascular thrombosis is the main manifestation of the disease, other rarer complications have also been described. Avascular necrosis (AN) is considered a rare manifestation of APS. The aim of our case series is to study patients with APS and AN. Methods: A retrospective study was performed on 80 patients diagnosed with APS. Results: AN was observed in 3 patients out of 80 diagnosed with APS. AN of the femoral head was observed in all cases. Case (1): A 54-year-old woman presented due to multiple ischemic infarctions in the brain, as detected in magnetic resonance imaging of the brain, Raynaud’s phenomenon, and AN of the femoral head. In laboratory testing, a prolongation of activated partial thromboplastin time was recorded. A heterozygous mutation was also found in the gene MTHFR C677T, and the patients was positive for lupus anticoagulant (LA). The patient was given clopidogrel and acenocoumarol. Case (2): A 52-year-old man was diagnosed with APS, based on the clinical presentation (stroke) and positivity for LA and anti-β2GPI (anti-β2 glycoprotein I antibody). In his medical history, episodes of vertigo and an episode of AN of the femoral head 2 years ago were described. Case (3): A woman aged 43 years presented due to AN of the femoral head. Due to suspected APS, immunological testing was performed, and positivity for LA and IgM anticardiolipin antibodies was detected. She was treated with acenocoumarol. Conclusions: AN is a rare clinical manifestation of APS, which may precede the diagnosis of APS for many years. Full article

Background: In rare cases, isolated hypoglossal palsy may arise from dissection and/or pseudoaneurysm of either the internal carotid artery (ICA) or the vertebral artery (VA). However, the mechanism of this pathology has not been elucidated, and no high-quality randomized data exist to guide its management. Case Description: A 43-year-old man without a significant medical history presented with signs of isolated right hypoglossal palsy following a vigorous coughing episode. Imaging demonstrated dissection and pseudoaneurysm of the left ICA in addition to dissection of the right VA. After 2 weeks on 325 mg aspirin daily, the patient presented with left (rather than right) tongue symptoms and worsening ICA and VA stenosis. While on 325 mg aspirin plus 75 mg clopidogrel daily without additional endovascular intervention, the patient improved with no residual symptoms at 6 weeks from symptom onset. Conclusions: Acute hypoglossal nerve palsy may present with ipsilateral swelling, which could be mistaken for contralateral atrophy. We suggest ordering a CT angiogram initially to delineate a potential ICA versus VA dissection, as well as to rule out other etiologies. In our case, dissection and pseudoaneurysm from the ICA likely led to hypoglossal palsy through a mass effect on the nerve. Our comprehensive literature review favors initial management with dual-antiplatelet agents, and to then escalate to procedural interventions if symptoms worsen. Full article

Background: Coexisting coronary artery disease and critical carotid stenosis present challenges in revascularization, particularly in urgent cases requiring surgery. Combining carotid artery stenting (CAS) with coronary artery bypass grafting (CABG) has gained popularity. Methods: This study analyzed 36 patients who underwent simultaneous CAS and CABG from 2014 to 2024. CAS was performed first, with the patient awake for real-time neurocognitive assessment. A clopidogrel loading dose was administered three hours post-surgery. From postoperative day 1, dual antiplatelet therapy was initiated. Results: The median age was 72 years (64–77) and 22.2% were females. The median EuroSCORE II was 2.80 (2.06–3.58). Nine patients (25%) underwent associated procedures. The median cardiopulmonary bypass and cross-clamp times were 66 (54–89) and 51 (41–72) minutes. We observed no in-hospital mortality and no postoperative stroke. The median postoperative bleeding in 24 h was 500 mL and only one (2.8%) patient needed resternotomy for bleeding. The median ventilation time was 9 h (6–12). The median intensive care unit and postoperative length of stay were 2 (2–4) days and 8 (7–11) days, respectively. The median follow-up time was 6 years. Survival at 1, 5, and 10 years was 93.7%, 81.5%, and 60.2%, respectively, while freedom from PTCA/PCI at 1, 5, and 10 years was 100%, 96.7%, and 87.5%, respectively. Conclusions: Simultaneous CAS and CABG is a safe and effective procedure with low in-hospital mortality and morbidity. Our protocol carries a low risk of perioperative stroke. Antiplatelet therapy administration on the day of surgery does not increase the risk of postoperative bleeding. Full article

(1) Background: Aspirin and clopidogrel have been found helpful in improving clinical outcomes among patients with chronic obstructive lung disease (COPD). However, the evidence on the efficacy of aspirin and/or clopidogrel on clinical outcomes has not been synthesized and summarized in the prior reviews. Hence, we undertook a meta-analysis of the research studies examining the effect of aspirin and/or clopidogrel on varying clinical outcomes among COPD patients; (2) Methods: Using key search terms, we searched databases, including MEDLINE, CINAHL, Google Scholar, and EMBASE to find observational studies and RCTs. Our search was limited to research written in English. We used a random effect model to calculate the 95% confidence intervals and pooled hazard ratio; (3) Results: We included 12 eligible research studies (33,8008 patients) in the current meta-analysis. Among COPD patients, the hazard of all-cause mortality among users of aspirin or clopidogrel was 17% lower (HR: 0.83; 95% CIs (0.70, 0.97; I² = 73%, X2: 33.34) compared to non-users of anticoagulants (aspirin or clopidogrel). The hazard of dyspnea among users of aspirin or clopidogrel was 3% lower (HR: 0.97; 95% CIs (0.27, 3.49; I² = 93%, X2: 42.15) compared to non-users of anticoagulants (aspirin or clopidogrel). There was no statistically significant effect of aspirin on other clinical outcomes such as myocardial infarction (HR: 2.04; 95% CIs (0.02, 257.33) and major bleeding (HR: 1.93; 95% CIs (0.07, 1002.33). The funnel plot and Egger’s regression test did not show any evidence of publication bias; (4) Conclusions: Overall, we found a positive and beneficial effect of aspirin and/or clopidogrel in reducing all-cause mortality among COPD patients. However, there is uncertainty of evidence for other clinical outcomes such as exacerbation of dyspnea, myocardial infarction, and major bleeding. A limited number of studies examining other clinical outcomes warrant conducting more robust epidemiological studies to assess the efficacy and safety of aspirin and clopidogrel on other clinical outcomes among COPD patients. Full article

The crystal structures of two pseudopolymorphic forms of S(+)clopidogrel–picrate are reported. Form 1 crystallizes in the monoclinic space group P2₁ with an ionic couple S(+)ClopH+·Pic⁻ and a molecule of solvent ethanol in the asymmetric unit, while Form 2 crystallizes in the monoclinic space group C2 with two ionic couples in the asymmetric unit. The configurations and conformations of the ionic couples, held together by ionized +N-H···O hydrogen bonds, are nearly identical in the structures. The self-assembly properties are compared with reported clopidogrel salts, including those used in pharmaceutical formulations. The hydrogen bonds are discussed in reference to the general corresponding behavior of the N-bases picrates and the properties of the acid-base coformers. The preparations of the pseudopolymorphs were optimized toward two different methods: solvent evaporation and mechanochemical treatment. Reproducibility to generate the single crystalline phases was confirmed by thermal and vibrational spectroscopic properties. Periodic third-order density-functional tight binding (DFTB3) calculations predict rather small energy difference between the two pure phases of polymorphs 1 and 2. However, the included solvent molecules in Form 1 decrease the lattice energy for ~10.5 kcal mol⁻¹, which leads to a lower ΔE_latt. lattice energy in comparison to Form 2 (by ~7.3 kcal mol⁻¹). All predicted trends are in line with the experimentally observed formation of Form 1 instead of its simulated non-solvated Form 1. Full article

(1) Background: The optimal antiplatelet therapy for end-stage kidney disease (ESKD) patients on chronic dialysis presenting with acute or chronic coronary syndromes (ACS or CCS) remains uncertain. This meta-analysis aimed to compare the efficacy and safety endpoints of ticagrelor and clopidogrel in ESKD patients requiring dialysis and presenting with ACS or CCS. (2) Methods: Studies were included comparing ticagrelor and clopidogrel in ESKD patients on chronic dialysis with ACS or CCS. The primary composite efficacy outcome was a combination of all-cause and cardiovascular mortality, recurrent myocardial infarction or coronary revascularization, and ischemic or hemorrhagic stroke. The primary safety outcome was major and non-major bleeding events. (3) Results: Five observational studies met the eligibility criteria. The pooled analysis showed no significant difference in the primary composite efficacy outcome between ticagrelor and clopidogrel (p = 0.40). Similarly, the 2 groups had no significant differences in all-cause mortality (p = 0.82) or cardiovascular mortality (p = 0.79). Ticagrelor did not show a significantly different risk of coronary revascularization (p = 0.35) or recurrent myocardial infarction (p = 0.41) compared to clopidogrel. Also, the risk of stroke was similar (p = 0.21). The 2 groups had no significant difference in the primary composite safety outcome (p = 0.22) or major bleeding events (p = 0.27). (4) Conclusions: In ESKD patients on chronic dialysis with ACS or CCS, there was no significant difference in efficacy or safety outcomes between ticagrelor and clopidogrel. Further randomized controlled trials are needed to establish the optimal antiplatelet therapy in this population. Full article

The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190–460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies. Full article

Background: Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin release. Methods: TIRATROP (TIcagrelor in Rotational Atherectomy to reduce TROPonin enhancement) is a multicenter double-blind randomized controlled trial that included 180 patients with severe calcified lesions requiring RA who received either clopidogrel (300 mg loading dose, then 75 mg/d) or ticagrelor (loading dose 180 mg then 90 mg twice daily). Blood samples were collected at the beginning (T0), and 6, 12, 18, 24 and 36 h after the procedure. Primary end point was troponin release within the first 24 h using area under the curve analysis (troponin level as a function of time). Results: The mean age of patients was 76 ± 10 years, 35% had diabetes. RA was used to treat 1, 2 or 3 calcified lesions in 72%, 23% and 5% of patients, respectively. Troponin release within the first 24 h was similar in both the ticagrelor (adjusted mean ±SD of ln AUC 8.85 ± 0.33) and the clopidogrel (8.77 ± 0.34, p = 0.60) arms. Independent predictors for troponin enhancement were acute coronary syndrome presentation, renal failure, elevated C-Reactive protein and multiple lesions treated with RA. Conclusion: Troponin release did not differ among treatment arms. Our results suggest that greater platelet inhibition does not affect periprocedural myocardial necrosis in the setting of RA. Full article

(1) Background: Coronary artery stenting leads to local inflammation, disturbs vasomotion, and slows endothelialization, increasing vascular thrombus risk. We used a pig stenting coronary artery model to assess how peri-interventional triple therapy with dabigatran ameliorates these effects. (2) Methods: In a total of 28 pigs bare-metal stents were implanted. Four days before the percutaneous coronary intervention (PCI), we started 16 of the animals on dabigatran, maintained through 4 days after the procedure. As controls, the remaining 12 pigs received no therapy. In both groups, dual antiplatelet therapy (DAPT) (clopidogrel, 75 mg plus aspirin, 100 mg) was administered until animals were euthanized. Just after the PCI and on day 3 after the procedure, we performed optical coherence tomography (OCT) in eight animals in the dabigatran group and four controls and euthanized them. We followed the eight remaining animals in each group with OCT and angiography for one month before euthanizing them and performed in vitro myometry and histology on harvested coronary arteries from all animals. (3) Results: The dabigatran group showed a significantly increased vasoconstriction at 3 days after PCI (10.97 ± 3.85 mN vs. 7.32 ± 5.41 mN, p = 0.03), but we found no differences between endothelium-dependent and -independent vasodilatation. We also found no group differences in OCT, quantitative angiography, or histomorphometry findings. (4) Conclusions: Starting a short course of dabigatran just before PCI and continuing for a 3-day window along with usual post-PCI DAPT is associated with enhanced vasoconstriction after bare-metal stent implantation without reducing neointimal formation at one month. Full article

There is limited information about diurnal changes in fibrinolysis parameters after acute myocardial infarction (AMI) and their relationship with on-treatment platelet reactivity. The aim of this study was to assess tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), α2-antiplasmin (α2-AP) activity, and plasmin–antiplasmin (PAP) complexes in 30 AMI patients taking dual antiplatelet therapy (DAPT), i.e., acetylsalicylic acid and clopidogrel. Fibrinolytic parameters were assessed at four time points (6 a.m., 10 a.m., 2 p.m., and 7 p.m.) on the third day after AMI using immunoenzymatic methods. Moreover, platelet reactivity was measured using multiple-electrode aggregometry, to assess potential differences in fibrinolytic parameters in low/high on-aspirin platelet reactivity and low/high on-clopidogrel platelet reactivity subgroups of patients. We detected significant diurnal oscillations in t-PA and PAI-1 levels in the whole study group. However, PAP complexes and α2-AP activity were similar at the analyzed time points. Our study reveals a potential impact of DAPT on the time course of fibrinolytic parameters, especially regarding clopidogrel. We suggest the presence of diurnal variations in t-PA and PAI-1 concentrations in AMI patients, with the highest levels midmorning, regardless of platelet reactivity. Significantly elevated levels of PAI-1 during the evening hours in clopidogrel-resistant patients may increase the risk of thrombosis. Full article