Combination therapy for Sneddon syndrome to reduce the incidence of cerebrovascular complications.

BACKGROUND: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long-term results. PATIENTS AND METHODS: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. RESULTS: During the 99.7 patient-years of follow-up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient-year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient-year. After discontinuation of alprostadil therapy, eight events occurred in three patients. CONCLUSIONS: Combination therapy reduces the long-term incidence of ischemic events in patients with primary Sneddon syndrome.

An update on oral antiplatelet drug interactions with proton pump inhibitors: what are the risks?

INTRODUCTION: Aspirin and anti-P2Y12 are widely prescribed in cardiovascular patients, often in combination with proton pump inhibitors (PPIs) to limit the risk of upper gastrointestinal bleedings. The potential interaction between PPIs and antiplatelet agents has been widely discussed, but doubts remain as to whether PPIs may reduce the cardiovascular protection provided by aspirin, prasugrel, ticagrelor, and clopidogrel. AREAS COVERED: Many pharmacokinetic (PK) and pharmacodynamic (PD) studies have confirmed the interaction, especially between PPIs and clopidogrel, but with uncertain consequences on clinical outcomes. Therefore, we aimed to summarize the evidence for the widespread combined use of oral antiplatelet drugs and PPIs, to outline the current evidence supporting or opposing drug-drug interaction, and to discuss the clinical implications of such interactions. EXPERT OPINION: A large body of evidence describes the PK/PD interaction of antiplatelet drugs with PPIs and its potential role in increasing clinical cardiovascular adverse events, but no solid clinical data have confirmed these effects. In the light of the published studies, there seems to be no restriction on the choice of PPI with aspirin, prasugrel and/or ticagrelor. The choice of a PPI with no (or minimal) interference with the hepatic cytochrome P450 2C19 is preferred in patients receiving clopidogrel.

Predictors of symptomatic intracerebral hemorrhage after endovascular treatment for acute ischemic stroke due to tandem lesion in anterior circulation.

BACKGROUND: Endovascular treatment (EVT) of tandem lesion (TL) in the anterior circulation acute ischemic stroke (IS) usually requires periprocedural antithrombotic treatment and early initiation of dual antiplatelet therapy (DAPT) after carotid stenting. However, it may contribute to an occurrence of symptomatic intracerebral hemorrhage (SICH) in some cases. We investigated factors influencing the SICH occurrence and assessed the possible predictors of SICH after EVT. METHODS: IS patients with TL in the anterior circulation treated with EVT were enrolled in the multicenter retrospective ASCENT study. A good three-month clinical outcome was scored as 0-2 points in modified Rankin Scale (mRS) and recanalization using the TICI scale. SICH was assessed using the SITS-MOST criteria. Logistic regression analysis was used for the assessment of possible predictors of SICH with adjustment for potential confounders. RESULTS: In total, 300 (68.7% males, mean age 67.3 ± 10.2 years) patients with median of admission NIHSS 17 were analyzed. Recanalization (TICI 2b-3) was achieved in 290 (96.7%) patients and 176 (58.7%) had mRS 0-2. SICH occurred in 25 (8.3%) patients. Patients with SICH did not differ from those without SICH in the rate of periprocedural antithrombotic treatment (64 vs. 57.5%, p=0.526) and in the rate of DAPT started within the first 12 hours after EVT (20 vs. 42.2%, p=0.087). After adjustment, admission NIHSS and admission glycemia were found as the only predictors of SICH after EVT. CONCLUSION: Admission NIHSS and glycemia were found as the only predictors of SICH after EVT for TL. No associations between periprocedural antithrombotic treatment, early start of DAPT after EVT and SICH occurrence were found.

A Closer Look into Gastrointestinal Bleeding in Heart Failure Patients.

BACKGROUND: The frequency and risk factors for gastrointestinal bleed (GIB) in patients with heart failure with reduced ejection fraction (HFrEF) have not been extensively researched. OBJECTIVE: We aim to assess the frequency of GIB in this subset of patients and identify potential risk factors for bleeding. This study will evaluate the frequency of commonly used antiplatelet and anticoagulation agents in the HFrEF population, as well as look at some of the endoscopic features of the GIB. METHODS: A retrospective cohort analysis of 670 patients admitted between November 2021 to August 2023 to a single urban, tertiary teaching institution with acute HFrEF ICD-10 codes. Upper or lower GIB (hematemesis, coffee ground emesis, melena or hematochezia during admission) was identified on a manual chart review. Patients with GIB were defined as our cases. No GIB was defined as our controls. Sub analysis included comparing the use of anticoagulant and antiplatelet between the cohort. Independent t test assessed statistical differences in the case and control groups RESULTS: Out of the 670 patients, 134 (20%) were identified with GIB. The cases were older than the controls (median age 77 vs. 70 years) (p = 0.001), had a lower hemoglobin (9 g/dL vs. 12 g/dL) (p =<0.05), and had higher BNP levels (7,938 pg/ml vs. 6472 pg/ml) (IQR: 3,239, 23,701) (p =<0.01). Among the anticoagulant users, 64% of cases were on an anticoagulant compared to 42% of the controls (p<0.05). Among the antiplatelet users, 68% of the controls were on one or more antiplatelet agents, compared to 52% in the controls (p = 0.01). When combining AC and AP treatment, there was no statistical difference between cases and controls. Ninety-three (69%) patients from cases had cross-sectional imaging with only 23 (25%) showing abnormal findings which included diverticulosis, colitis, and GI masses. When comparing upper endoscopy findings, the presence of esophageal diseases (esophagitis and esophageal varices) and gastric/duodenal diseases (gastritis, gastric ulcer, duodenal ulcer and AVM) were significantly higher in cases compared to controls (p < 0.05). In addition to the colonoscopy findings, polyps and diverticulosis were more prevalent in the cases compared to the controls (p = 0.01). CONCLUSION: Heart failure patients are at risk of developing GIB. Age and high BNP on admission are risk factors for GIB, the higher the BNP levels the higher risk of GIB. Anticoagulant and antiplatelet use are associated with a higher risk of bleeding. However, the addition of dual antiplatelet therapy or concurrent antiplatelet and anticoagulation does not increase the risk of GIB. Some of the most common upper endoscopy findings include esophagitis/gastritis and esophageal/gastric ulcer. In terms of colonoscopy, findings include colonic mass, diverticulosis and hemorrhoids.

Antiplatelet therapy to prevent ischemic events in giant cell arteritis: protocol for a systematic review and meta-analysis.

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. Presenting features include new-onset headaches, constitutional symptoms, jaw claudication, polymyalgia rheumatica, and visual symptoms. Arterial inflammation with subsequent stenosis and occlusion may cause tissue ischemia, leading to blindness, strokes, and myocardial infarction. Oral antiplatelet therapy has been hypothesized to reduce GCA-related ischemic events. However, previous studies have demonstrated conflicting results regarding the efficacy of antiplatelet agents in GCA. The objective of this systematic review is to assess the safety and efficacy of antiplatelet therapy for the prevention of these events in adults with giant cell arteritis. METHODS: In this systematic review, we will include randomized controlled trials (RTCs), quasi-randomized trials, non-randomized intervention studies, cohort studies, and case-control studies on patients with new-onset or relapsing GCA. The intervention of interest will be pre-existing use or initiation of an oral antiplatelet medication (aspirin, clopidogrel, prasugrel, or ticagrelor) at GCA onset or relapse. The comparator of interest will be the absence of antiplatelet therapy. Endpoints will be evaluated after 6 and 12 months of follow-up. The primary outcome will be GCA-related ischemic events, including permanent blindness, stroke, myocardial infarction, and ischemic event-related deaths. Adverse events such as major bleeding and death caused by a bleeding event will be assessed. DISCUSSION: GCA-related ischemic events are catastrophic, sudden, often irreversible, and lead to significant morbidity. Antiplatelet agents are affordable, accessible, and could be effective for the prevention of these events. Nevertheless, the potential benefits of platelet aggregation inhibition must be weighed against their associated risk of bleeding. Assessing the efficacy and safety of antiplatelet therapy in GCA is therefore clinically important. SYSTEMATIC REVIEW REGISTRATION: Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42023441574.

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial.

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

Anticoagulation and Antiplatelet Regimen in Cardiac Transplant. Clinical Characteristics, Outcomes, and Blood Product Transfusion.

BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.

Treatment options for patients with CADASIL and large-scale cerebral infarction: mechanical thrombectomy and antiplatelet therapy-A case report.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant inherited arterial disease, with lacunar infarction resulting from intracranial small vessel lesions being the most prevalent clinical manifestation of CADASIL. However, large-scale cerebral infarction caused by intracranial non-small vessels occlusion is relatively uncommon, and reports of vascular intervention and long-term antiplatelet drug treatment for patients with CADASIL and large-scale cerebral infarction are rarer. Methods: We reported a 52 year-old male who experienced a significant cerebral infarction due to an occlusion in the second segment of the left middle cerebral artery, 4 months subsequent to being diagnosed with CADASIL. Following the benefit and risk assessment, the patient underwent intracranial vascular thrombectomy and balloon dilation angioplasty. Subsequently, he was administered dual antiplatelet therapy for 3 months, followed by mono antiplatelet therapy. Results: After undergoing intracranial vascular intervention and receiving antiplatelet therapy, significant improvement in the symptoms were observed. The National Institutes of Health Stroke Scale score decreased from 6 to 2 points, and no bleeding lesions were detected on the head computed tomography during regular follow-up visits after discharge. Conclusion: Our case highlights the possibility that patients with CADASIL may also encounter extensive cerebral infarction resulting from stenosis or occlusion of intracranial non-small vessels. Considering the specific circumstances of the patient, intravascular intervention and antiplatelet therapy can be regarded as viable treatment options for individuals with CADASIL.

Preventive medication efficacy after 1-year follow-up for graft failure in coronary artery bypass surgery patients: Bayesian network meta-analysis.

To compare preventive medications against graft failures in coronary artery bypass graft surgery (CABG) patients after a 1-year follow-up. Systematic review with Bayesian network meta-analysis and meta-regression analysis. We searched PubMed, Scopus, and Web of Science databases in February 2023 for randomized controlled trials, comparing preventive medications against graft failure in CABG patients. We included studies that reported outcomes at 1 year after surgery. Our primary outcome was graft failure After screening 11,898 studies, a total of 18 randomized trials were included. Acetylsalicylic acid (ASA) [odds ratios (OR) 0.51, 95% credibility interval (CrI) 0.28-0.95, meta-regression OR 0.54, 95% CrI 0.26-1.00], Clopidogrel + ASA (OR 0.27, 95% CrI 0.09-0.76, meta-regression OR 0.28, 95% CrI 0.09-0.85), dipyridamole + ASA (OR 0.50, 95% CrI 0.30-0.83, meta-regression OR 0.49, 95% CrI 0.26-0.90), ticagrelor (OR 0.40, 95% CrI 0.16-1.00, meta-regression OR 0.43, 95% CrI 0.15-1.2), and ticagrelor + ASA (OR 0.26, 95% CrI 0.10-0.62, meta-regression OR 0.28, 95% CrI 0.10-0.68) were superior to placebo in preventing graft failure. Rank probabilities suggested the highest likelihood to be the most efficacious for ticagrelor + ASA [surface under the cumulative ranking (SUCRA) 0.859] and clopidogrel + ASA (SUCRA 0.819). The 95% CrIs of ORs for mortality, bleeding, and major adverse cardio- and cerebrovascular events (MACE) were wide. A trend towards increased bleeding risk and decreased MACE risk was observed when any of the medication regimens were used when compared to placebo. Sensitivity analysis excluding studies with a high risk of bias yielded equivalent results. Of the reviewed medication regimens, dual antiplatelet therapy combining ASA with ticagrelor or clopidogrel was found to result in the lowest rate of graft failures.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Incidence and clinical impact of inappropriate periprocedural and perioperative management of antiplatelet therapy.

BACKGROUND AND AIMS: There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in "real life" in Spain. METHODS: A prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. RESULTS: We included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. CONCLUSIONS: Despite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the "real world" remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.

The influence of P2Y12 gene polymorphisms on clopidogrel therapy in patients after percutaneous coronary intervention.

Aim: We aimed to define the influence of P2Y12 polymorphisms (rs6801273, rs2046934, and rs6809699), diabetes, hypertension, obesity, hypercholesterolemia, statins intake, and smoking habit on clopidogrel therapy in patients undergoing percutaneous coronary intervention. Materials & methods: We used PCR-RFLP and PCR-ASO for P2Y12 genotype analysis. The effectiveness of the therapy was measured with the VerifyNow method and defined in platelet reactivity units. Results: Studied polymorphisms had no statistically significant influence on PRU before (PRU0) and 6 months (PRU6) after the procedure. H1/H1 diabetic carriers had significantly higher PRU6 values than patients without diabetes. Obese H1/H2 subjects had significantly lower PRU6 values than H1/H2 non-obese carriers. Conclusion: We found that obesity and diabetes may influence the long-term outcome of antiplatelet therapy.

Clopidogrel is a medicine that prevents platelets in the blood from clumping and blocking arteries. When the structure of the protein (e.g., P2Y12), responsible for response to clopidogrel is changed, we can observe less efficient therapy. Said changes can be caused for example by genetic polymorphisms, which are two or more variants of the same gene. This is why we wanted to check the impact of P2Y12 polymorphisms. We also wanted to check the impact of diabetes, high blood pressure, being overweight, high cholesterol blood level, cholesterol-reducing drugs, and smoking habits on clopidogrel treatment in patients after a procedure that unblocks blood vessels of the heart to restore its blood supply (percutaneous coronary intervention). We measured the efficacy of the treatment with platelet reactivity units (PRU). Studying polymorphisms had no impact on treatment efficacy before (PRU0) and 6 months (PRU6) after the medical procedure. We found that diabetes can cause higher platelet reactivity after 6 months of therapy. We noticed that being overweight may also be important, as obese patients had lower platelet reactivity values.

Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).

Effects of dual antiplatelet therapy (DAPT) compared to single antiplatelet therapy (SAPT) in patients with traumatic brain injury.

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.

Different antithrombotic strategies after coronary artery bypass grafting to prevent adverse events: a retrospective analysis.

OBJECTIVE: Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery. METHODS: This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias. RESULTS: A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events. CONCLUSIONS: Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.

Patient and Physician Perspectives on the Benefits and Risks of Antiplatelet Therapy for Acute Coronary Syndrome.

This article is co-authored by a patient with acute coronary syndrome (ACS) who is receiving long-term antiplatelet therapy in the USA and a cardiologist who routinely treats patients with ACS. The patient describes his experience from diagnosis to the present day and discusses his concerns regarding treatment and management of the condition, including the balance between the benefits and risks of antiplatelet therapy. The patient also describes his work as an advocate for cardiac health. The physician perspective on treating and managing patients with ACS is provided by a cardiologist based in the USA who is and was not involved in this patient's care. The physician reviews the benefits and risks of antiplatelet therapies for the treatment of patients with ACS and discusses his own clinical experience of managing these patients, including how issues such as treatment adherence, as well as the potential inertia to prescribing certain medications that may be seen among physicians, could be overcome.

Antiplatelet therapies are commonly prescribed to patients who have experienced events termed "acute coronary syndrome" (ACS), such as a heart attack, to prevent further cardiovascular events. However, these medicines come with potential risks, such as bleeding. This article provides perspectives from a patient and a cardiologist on managing ACS, and the benefits and risks of antiplatelet therapies. Platelet inhibitors, which aim to prevent blood clots from forming, are the standard treatment for ACS. Different types of platelet inhibitors are used, including treatments known as P2Y12 inhibitors as well as treatments referred to as platelet aggregation inhibitors. Clinical trials have tested different combinations and durations of antiplatelet therapies, and some trials have shown that changing to P2Y12 inhibitor treatment alone after receiving a combination of platelet inhibitors can reduce the risk of cardiovascular events without increasing the risk of bleeding. Treatment guidelines recommend at least 12 months of platelet inhibitors for patients with ACS; however, treatment decisions should be individualized based on the patient's risk profile. Despite the evidence supporting their benefits, some physicians remain reluctant to prescribe potent P2Y12 inhibitors, preferring older, less potent options. Treatment adherence is also challenging, and is influenced by factors such as bleeding, education level, and cost. Improved education about the benefits and risks of antiplatelet therapies may help to address these issues and improve outcomes for patients with ACS. The perspectives of both the patient and the physician contribute to an increased understanding of ACS management and the challenges faced by patients and health care providers.

Dual Antiplatelet Non-Responder: Resistance to Clopidogrel and Ticagrelor.

Background: Dual antiplatelet therapy is often required for neurointerventional procedures, especially when a stent or flow diverter is placed in the cervical and intracranial vessels. Patients are usually started on aspirin and clopidogrel given the simplicity of the once daily regimen with reasonable cost. Unfortunately, about a third of patients do not show the desired antiplatelet response to clopidogrel and another agent needs to be introduced. Ticagrelor is a potent antiplatelet medication that has a favorable pharmacological profile and has emerged as a reliable alternative to clopidogrel in recent years. Despite ticagrelor non-responders being rare, they do exist, and identification of these patients is important. Results: A 74-year-old female was incidentally found to harbor a right posterior communicating aneurysm which was successfully treated electively with stent-assisted coiling. Platelet inhibition testing revealed non-responsiveness to Clopidogrel. Ticagrelor was initiated but the patient's platelet reactivity unit remained in the normal range. Management algorithms to maximize a patient's ticagrelor response by facilitating enteral absorption were applied but no platelet inhibition was achieved. The patient was eventually identified as a true ticagrelor non-responder. Conclusion: Resistance to antiplatelet medication can result in devastating complications with permanent neurological deficits. Ticagrelor non-responders are rare but do exist. Platelet inhibition testing should be part of the preprocedural workup for neurointerventions.

Long-term outcomes among ischemic stroke TOAST subtypes: A 12-year Cohort study in China.

BACKGROUND: Disparities in short-term ischemic stroke (IS) prognosis among Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes were observed. Notably, little is known about the long-term prognosis of different subtypes in China. We aim to investigate the long-term outcome in IS patients and try to explore the potential interactive effects between IS subtypes and antithrombotic therapy. METHODS: This is a prospective cohort of stroke survivors. Patients diagnosed with first-ever IS at the Department of Neurology, West China Hospital, Sichuan University from January 2010 to December 2019 were recruited. They were followed until September 2022 to assess recurrence, mortality, and functional recovery. The multivariate Fine-Gray model assessed stroke recurrence, while Cox regression estimated hazard ratios. Modified Rankin Scale scores(mRS) were analyzed using the generalized linear mixed effects model. RESULTS: At baseline, 589 of 950 participants (62.00 %) were male. The longest follow-up was 150 months, the shortest was 1.5 months, and the median follow-up was 81.0 months. Cardio-embolism (CE) bore the highest mortality risk compared to large artery atherosclerosis (LAA) (HR=4.43,95 %CI 1.61-12.23). Among survivors on anticoagulant therapy, CE exhibited a reduced risk of mortality (HR = 0.18, 95 % CI 0.04-0.80). In function recovery, small artery occlusion (SAO) demonstrated more favorable prognostic outcomes (ß=-2.08, P<0.01, OR=0.13,95 %CI 0.03-0.47). Among survivors taking antiplatelet drugs, SAO demonstrated a slower pace of functional recovery compared to LAA (ß=1.39, P=0.05, OR=3.99,95 %CI 1.01-15.74). CONCLUSIONS: Long-term outcomes post-first IS vary among TOAST subtypes. Anticoagulant therapy offers long-term benefits among patients of the CE. However, prolonged administration of antiplatelet drugs among SAO patients may be limited in improving function recovery. Physicians should carefully consider treatment options for different IS subtypes to optimize patient outcomes and stroke care effectiveness.

Beyond RCTs: Short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack.

BACKGROUND AND PURPOSE: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs. METHODS: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment. RESULTS: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding. CONCLUSIONS: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.

Adenosine in Interventional Cardiology: Physiopathologic and Pharmacologic Effects in Coronary Artery Disease.

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.