Combination Of Low-dose Aspirin Research Articles

Adjunctive Cilostazol in Patients With High Residual Platelet Reactivity After Drug-Eluting Stent Implantation: A Randomized, Open-Label, Single-Center, Prospective Study (ADJUST-HPR).

Cilostazol as an adjunct to dual antiplatelet therapy (DAPT) postcoronary stenting may further reduce vascular occlusion risks. The aim of this study was to assess the impact of cilostazol on high residual platelet reactivity (HRPR) in patients undergoing drug-eluting coronary stent implantation. In a randomized, open-label, single-center, prospective study, the degree of platelet inhibition by cilostazol 100 mg twice daily was assessed on top of conventional DAPT compared with standard clopidogrel and low-dose aspirin combination in poststent patients with HRPR. HRPR was defined as P2Y12 units (PRU) > 240 as measured by the VerifyNow P2Y12 assay. In addition, the platelet activity was assessed by light transmittance aggregometry (LTA) and Multiplate electrode analyzer (MEA). The total of 148 patients were screened, and HRPR was observed in 64 (43.2%). Those were randomized for DAPT versus triple therapy (TAPT). After 30 days, TAPT group exhibited significantly lower rate of HRPR when assessed by all 3 devices (VerifyNow: 40.0 vs. 66.7% P = 0.04, LTA: 6.7 vs. 30.0% P = 0.02, MEA: 10.0 vs. 30.0% P = 0.05 L all vs. DAPT). Also, higher absolute mean difference in TAPT versus DAPT group after 30 days (VerifyNow: 71.3 ± 38.2 vs. 24.6 ± 40.2 P < 0.001, LTA: 23.9 ± 15.1 vs. 9.4 ± 11.8 P < 0.001, MEA: 9.3 ± 12.9 vs. 2.4 ± 17.3 P = 0.08) was observed. Cilostazol in addition to standard DAPT reduces the incidence of HRPR and diminishes further platelet activity in poststent patients. Whether this favorable laboratory finding will affect clinical outcomes requires an adequately powered randomized trial.

Low-Dose Aspirin in Combination with Transarterial Chemoembolization in Treatment of Unresectable Hepatocellular Carcinoma

Low-Dose Aspirin in Combination with Transarterial Chemoembolization in Treatment of Unresectable Hepatocellular Carcinoma

Comparison of the Degree of Gastric Mucosal Injury between Patients Who Are Receiving Dual Antiplatelet Therapy or Single Antiplatelet Therapy.

Background: Patients taking low-dose aspirin have a higher incidence of gastroduodenal ulcers and higher risk of upper gastrointestinal bleeding than patients who do not. Thienopyridine antiplatelet agents may similarly cause bleeding gastroduodenal erosions and ulcers. The incidence of gastrointestinal bleeding is reported to be higher when these antithrombotic drugs are used in combination. Until now, most studies have focused on bleeding, and no study has compared the degree of gastric mucosal injury between patients receiving dual antiplatelet therapy (DAPT) and those receiving single antiplatelet therapy (SAPT) in real-world clinical practice. Aim: Our objective was to compare the degree of gastric mucosal injury in patients taking low-dose aspirin in combination with clopidogrel (one of the thienopyridine antiplatelet agents) with that of patients who were taking aspirin or clopidogrel as a single agent. Methods: Patients who were taking aspirin and/or clopidogrel and who underwent scheduled esophagogastroduodenoscopy between April 2015 and March 2020 were enrolled in this study. Endoscopic images were reviewed retrospectively, and the degree of gastric mucosal injury was assessed with the modified Lanza score (m-Lanza score). The m-Lanza score was compared between DAPT patients taking aspirin and clopidogrel and SAPT patients taking either aspirin alone or clopidogrel alone. Results: The m-Lanza scores of the DAPT group, the aspirin group, and the clopidogrel group were 1.67 ± 1.81 (mean ± standard deviation), 0.95 ± 1.61, and 0.72 ± 1.29, respectively. The m-Lanza score of the DAPT group tended to be higher than that of the aspirin group (p = 0.06) and was significantly higher than that of the clopidogrel group (p = 0.03). Conclusion: The degree of gastric mucosal injury in DAPT patients was significantly higher than that in patients using clopidogrel alone and tended to be higher than that in patients using aspirin alone in real-world clinical practice.

P-131 Low-dose aspirin in combination with transarterial chemoembolization in treatment of unresectable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt. Transarterial chemoembolization (TACE) is standard treatment for unresectable HCC. Recent studies showed that TACE refractoriness impairs survival of HCC patients. Various strategies under investigation aim to improve the outcome of TACE, Aspirin demonstrated chemopreventive, antithrombotic and anti-inflammatory properties Moreover, it has been reported that aspirin may reverse apoptosis resistance in HCC cell lines. This study includes 60 patients diagnosed as unresectable HCC indicted for TACE randomized in to two arms; control arm and aspirin arm. All patients have vascular and cellular compensated liver functions; platelets count ≥ 100,000, and normal prothrombin time. We excluded patients with bleeding tendency, gastrointestinal ulcers, portal hypertension, allergy or contraindication to aspirin. Aspirin arm patients received 75 mg of aspirin daily after meal for 3 months; we assessed feasibility, toxicity of aspirin, studied treatment response and disease progression. In this study there was no significant difference between the two arms regarding baseline patients’ characteristics. Regarding compliance to aspirin, 70% of patients were regular; regarding compliance to TACE, 60% of patients were compliant to TACE in aspirin arm versus 56.7% in control arm. Most of side effects of aspirin are of grade 1 gastrointestinal side effect. According to modified RECIST criteria, better responses achieved in aspirin arm; 10% of patients in aspirin arm had complete remission versus 6.7 %in control arm and 30% had partial response in aspirin arm versus 23% in control arm, 30% of patients in aspirin arm had disease progression versus 40% in control arm; however, the difference didn’t reach statistical significant level (p=0.806). 20% of patients in control arm developed portal vein thrombosis versus only 6.7% in aspirin arm. There was an improvement in progression free survival (PFS); the median PFS was not reached for aspirin arm versus 11 months for Control arm (P=0.035). The use of adjuvant aspirin with TACE in patients with HCC is feasible and may be associated with longer PFS and a tendency of better TACE responses; however, larger sample size may yield stronger results.

P2Y12 Inhibitors Exacerbate Low-dose Aspirin-induced Small Bowel Injury in Dual Antiplatelet Therapy.

Objective Antithrombotic drugs are being used increasingly frequently to prevent cardiovascular diseases. Few studies have evaluated small bowel mucosal injury induced by dual antiplatelet therapy (DAPT). The aim of the present study was to evaluate small bowel mucosal injury induced by DAPT compared with other antithrombotics using video capsule endoscopy (VCE). Methods The study included chronic users of antithrombotics who underwent VCE for obscure gastrointestinal bleeding between January 2007 and July 2018. We evaluated the instances of small bowel injury classified into erosions and ulcers. Results Overall, 183 patients (114 men and 69 women; mean age, 73.6 years old) were enrolled, and the study groups comprised 49 patients taking low-dose aspirin (LDA) only, 50 taking anticoagulants only, 37 being treated with DAPT, 33 on combined LDA and anticoagulants, and 14 taking P2Y12 inhibitors. Small bowel erosions and ulcers were most frequently observed in the DAPT group, with frequencies of 78.4% and 37.8%, respectively. Exacerbating factors of small bowel ulcers were DAPT [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.2-7.7] and age over 80 years old (OR 2.4, 95% CI 1.1-5.4). Conclusion P2Y12 inhibitors seem to exacerbate LDA-induced small bowel injury. Preventive strategies for small bowel injury induced by LDA, especially DAPT, are urgently required.

Management and Outcomes of Women with Antiphospholipid Antibodies or Antiphospholipid Syndrome during Pregnancy

BackgroundPregnant women with antiphospholipid antibodies (aPLs) or antiphospholipid syndrome have an increased risk for thrombosis. Although a combination of low-dose aspirin and unfractionated heparin (UFH) or low molecular weight heparin (LMWH) are usually prescribed in pregnancy, there is no consensus on optimal dosing of these agents. Despite the use of low-dose aspirin and LMWH, approximately 30% of women with a positive lupus anticoagulant (LA), underlying autoimmune disease, or a previous history of thrombosis have unfavorable outcomes.AimTo describe the management and outcomes of women with either aPLs or APS during pregnancy at a university medical center.MethodsWe conducted a retrospective cohort study of pregnant women with either aPLs or APS seen in our hematology clinic in consultation between January 2006 and August 2021. Data collected included demographics, reason for aPLs testing, personal or family history of thrombosis or autoimmune disease, and presence of other thrombophilias. Antiphospholipid antibodies included the LA, anti-cardiolipin (aCL) and anti-beta-2 glycoprotein 1 (ß2GP1) confirmed on two occasions at least 12 weeks apart. Data was collected on antithrombotic agents used during pregnancy, including aspirin, dose of LMWH, UFH and certolizumab. We recorded the following obstetric outcomes: live births, early delivery, fetal loss, early pregnancy loss <10 weeks gestational age (GA), pre-eclampsia, venous thromboembolic events (VTE), arterial thromboembolism (ATE), and post-partum hemorrhage (PPH). We compared management and outcomes in the presence or absence of LA. Statistical comparisons between groups were conducted with the Fisher's exact test.ResultsThere was a total of 202 pregnancies in 62 women with 11% of pregnancies achieved with assisted reproductive techniques. The most common reasons for aPLs testing were pregnancy loss (35%), VTE (23%), and ATE (8%). Antiphospholipid antibody profiles consisted of 56% triple positive, 8% positive LA plus either aCL or anti- ß2GP1, 13% positive LA alone and 22% with either double positive aCL and anti- ß2GP1 or single aCL or anti- ß2GP1. Twenty-tree percent of women had an additional inherited thrombophilia (Table 1). Of the 202 pregnancies, 52% resulted in live births, 20% in pregnancy loss <10 weeks, 12% in pregnancy loss >10 weeks, and 28% were either electively terminated, resulted on an ectopic pregnancy, or the outcome was unknown due to lost to follow up. Antithrombotic therapy was used in 47% of pregnancies: 26% used aspirin and LMWH, 10% used LMWH alone, and 7% used aspirin alone (Table 2). In 10% of pregnancies, patients were transitioned to UFH prior to delivery. Pre-eclampsia with or without HELLP syndrome occurred in 10% of pregnancies and maternal thromboembolic complications occurred in 6%. On analysis of outcomes stratified by LA status, there was a trend toward a higher rate of preterm births in the presence of a positive LA (Table 3). The rate of live births was increased with the use of antithrombotic therapy (Table 4).ConclusionPatients with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome had elevated rates of complications and adverse outcomes during pregnancy. LA positive status was associated with a trend toward a higher rate of preterm births. Further studies are needed to clarify the factors associated with adverse outcomes and optimal anticoagulation management. [Display omitted] DisclosuresDesancho: Sanofi-Genzyme: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:Certolizumab with the hypothesis of improving clinical outocomes

Effect of omega 3 fatty acids plus low dose aspirin as a host modulating agent in the treatment of periodontitis patients- A Systematic Review

Background and Objectives: Host Modulatory Therapy is a treatment modality for periodontal diseases. It aims at reducing the periodontal destruction and enhances the regenerative capacity of periodontal tissues. Various host modulating agents are used as an adjunct to scaling and root planing. Omega 3 Fatty acids and non-steroidal anti-inflammatory drugs like Aspirin modify the activity of inflammatory mediators and exert anti-inflammatory effect. The objective of the systematic review was to evaluate the effect of Omega 3 Fatty acids plus low dose Aspirin as adjunct to mechanical debridement in reduction of pocket depth in patients with periodontitis. Methods: In this systematic review, Randomized controlled trials in subjects with periodontitis in age group of 25-70 years were considered. Follow up period ranged from 6 weeks to 6 months. A systematic review of literature was performed using Pubmed, PMC, Google scholar, EBSCO host databases. Studies concerning the use of Omega 3 Fatty acids plus low dose Aspirin as host modulating agent in periodontitis treatment were selected. A total 2650 of studies were selected through search strategy and 5 articles which attained the inclusion criteria have been included in present systematic review. Results: Oral supplementation of omega 3 fatty acids in combination of low dose Aspirin as adjunct to mechanical debridement reduces the pocket depth during the 6 weeks to 6 months follow up period. Limitations: There are limited studies which are available. Also there is lack of data evaluating the long term follow up of the intervention. Conclusion: Use of omega 3 fatty acids and low dose aspirin in periodontitis patients improves periodontal status but further long-term studies need to be conducted.

Abstract P066: Purinergic Receptor Function In The Middle Cerebral Artery From Clopidogrel-treated Rabbits

Arterial thrombosis is the leading cause of death in the developed world and hypertensive patients are at an increased risk. Dual antiplatelet therapy, consisting of low-dose aspirin in combination with a P2Y 12 antagonist, is the most common preventative treatment for arterial thrombosis. Clopidogrel, a P2Y 12 antagonist, is associated with cerebral microbleeds and intracerebral hemorrhages. We have previously reported in rabbits that clopidogrel (3mg/kg) induces bleeding at lower doses than required to inhibit platelet aggregation, making it unlikely that the clopidogrel-mediated bleeding events are the result of platelet inhibition. I hypothesized that clopidogrel was acting on other purinergic receptors to impair artery function due to the structural similarity of the metabolites of clopidogrel. Purinergic receptors, P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 , are expressed in the endothelium of cerebral vessels. The purpose of this study was to determine the effects of clopidogrel on vascular function in response to activation of P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 . The middle cerebral artery (MCA) was used as it is the site most common for cerebrovascular events. New Zealand white rabbits (n=3) were treated for 3 days with vehicle or clopidogrel (3mg/kg/day) prior to MCA isolation. Myogenic tone was allowed to develop before assessing the response of the MCA to increasing concentrations (10 -9 -10 -5 M) of specific purinergic receptor agonists P2Y 1 : MRS 2365; P2Y 2 : MRS 2768; P2Y 4 : MRS 4062; P2Y 6 : MRS 2693. If myogenic tone was not generated the MCA was preconstricted with 10 -6 M serotonin. Response was analyzed by two-way ANOVA and compared to vehicle using Dunnett’s post-test. In all cases, p &lt; 0.05 denote statistical significance. Constriction was calculated as a percent change from baseline. Stimulation with the P2Y 4 agonist resulted in a mean maximal constriction of 28.95% (28.95 of 100) for vehicle and 52.72% (52.72 of 100) for 3mg/kg clopidogrel. There was no significant difference upon stimulation with the P2Y 1 , P2Y 2 , or P2Y 6 agonists compared to vehicle. These data suggest that clopidogrel has vascular effects on the P2Y 4 receptor expressed in the MCA and may explain the cerebral bleeding side effects observed.

Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin

ObjectiveTo evaluate T-helper cytokine responses in a short-term high fat diet (HFD) induced impaired glucose metabolism. To further evaluate the modulation of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines using short-term low-dose aspirin in combination with metformin. DesignTwo experiments were carried out in this study in order to evaluate the T-helper cytokine profiles in a state of impaired glucose metabolism. A total of 28 six-week-old male C57BL/6 mice were used in this study. In the first experiment, mice were fed either a high fat diet or low fat diet for a duration of 10 weeks. We then determined the Th1, Th2 and T-helper 17 (Th17) cytokine profiles. In the second experiment, we evaluated whether the short term 6-week treatment with low-dose aspirin in combination with metformin modulates T-helper cytokine profiles of the HFD-fed mice. MeasurementsIn the first experiment, we measured the body weights, blood glucose levels, insulin levels, lipid profiles and haematological parameters. We further performed oral glucose tolerance testing following an 8-hour fast and serum Th1, Th2 and Th17 cytokine levels were also determined following short-term 8-week diet-feeding and 6-week low-dose aspirin and combined metformin with low-dose aspirin treatment. ResultsHigh fat diet-feeding caused a marked increase in circulating peripheral blood lymphocytes, which was attenuated by short-term low-dose aspirin treatment. Moreover, the HFD feeding resulted in 2-fold increase in total cholesterol and a 4-fold increase in low-density lipoprotein cholesterol when compared to the low-fat diet-fed group (p < 0.05). In the high fat diet group, impaired glucose metabolism was associated with skewed Th2 responses without alterations in the Th1 and Th17 cytokine profiles. Interestingly the short-term treatment with low-dose aspirin showed no effect on the selected T-helper 1 cytokine IFN-Ƴ (P > 0.05). While the combination of low-dose aspirin with metformin considerably reduced the levels of serum IFN-Ƴ (P < 0.05). Furthermore low-dose aspirin treatment showed the modest attenuation of the selected Th2 cytokines, IL-10 and IL-13 when compared to low-dose aspirin with metformin (P < 0.01). ConclusionThe early immunological and metabolic changes that occur in a state impaired glucose tolerance are accompanied by the increased production of Th2 cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th2 cell responses.

Low-Molecular–Weight Heparin versus Unfractionated Heparin in Pregnant Women with Recurrent Abortion associated with Antiphospholipid Syndrome

Objectives: to compare the efficacy and safety of the combination of unfractionated heparin )UFH( and Low Dose Aspirin (LDA) with that of low-molecular-weight heparin )LMWH( and LDA in the management of pregnant women with recurrent pregnancy loss secondary to antiphospholipid syndrome (APS). Methods : In a randomized prospective study, 60 women with a history of 3 or more consecutive spontaneous abortions and positive antiphospholipid antibodies were assigned in equal numbers to receive either UFH (5000 units, twice daily) plus LDA, or LMWH (enoxaparin 40 mg, once daily) plus LDA as soon as pregnancy was diagnosed. Results: Twenty-four women in the LMWH group (80%) compared to 20 women in the UFH group (66.67%) delivered a viable infant (p >0.05). There was no significant difference in pregnancy complications or neonatal morbidity between the 2 groups. There were no incidences of excessive bleeding, thrombocytopenia, or osteoporotic fractures of excessive bleeding, thrombocytopenia, or osteoporotic fractures in either group. Conclusion: In this study, the use of LDA in combination with LMWH during pregnancy for the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome seems to be as safe as UFH plus LDA. Large randomized trials will be required to determine differences in outcome with LMWH and LDA compared with treatment with UFH combined with LDA in this group of patients.

Low-Molecular–Weight Heparin versus Unfractionated Heparin in Pregnant Women with Recurrent Abortion associated with Antiphospholipid Syndrome

Objectives: to compare the efficacy and safety of the combination of unfractionated heparin )UFH( and Low Dose Aspirin (LDA) with that of low-molecular-weight heparin )LMWH( and LDA in the management of pregnant women with recurrent pregnancy loss secondary to antiphospholipid syndrome (APS). Methods : In a randomized prospective study, 60 women with a history of 3 or more consecutive spontaneous abortions and positive antiphospholipid antibodies were assigned in equal numbers to receive either UFH (5000 units, twice daily) plus LDA, or LMWH (enoxaparin 40 mg, once daily) plus LDA as soon as pregnancy was diagnosed. Results: Twenty-four women in the LMWH group (80%) compared to 20 women in the UFH group (66.67%) delivered a viable infant (p >0.05). There was no significant difference in pregnancy complications or neonatal morbidity between the 2 groups. There were no incidences of excessive bleeding, thrombocytopenia, or osteoporotic fractures of excessive bleeding, thrombocytopenia, or osteoporotic fractures in either group. Conclusion: In this study, the use of LDA in combination with LMWH during pregnancy for the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome seems to be as safe as UFH plus LDA. Large randomized trials will be required to determine differences in outcome with LMWH and LDA compared with treatment with UFH combined with LDA in this group of patients.

In vivo effects of aspirin and cyclosporine on regulatory T cells and T-cell cytokine production in healthy dogs

Cyclosporine and aspirin are routinely used in combination to treat immune-mediated hemolytic anemia (IMHA) in dogs. Cyclosporine is a potent immunosuppressive agent that targets T cell production of the cytokines IL-2 and IFN-γ. Low-dose aspirin is often used to inhibit platelet function in dogs with IMHA, since these animals are prone to life-threatening thromboembolic disease. In rodents and humans, aspirin and cyclosporine have both been shown to variably affect T cell cytokine production, and also numbers of circulating regulatory T cells (Tregs). In dogs, it has not yet been determined if concurrent aspirin alters the effects of cyclosporine on T-cell cytokine expression, or if either drug influences Treg numbers.In a crossover study, seven healthy young adult dogs were given either oral high-dose cyclosporine (10 mg/kg Q12 h), oral low-dose aspirin (1 mg/kg Q24 h), oral high-dose aspirin (10 mg/kg Q12 h), or combined low-dose aspirin with cyclosporine, each for 8 days, with a washout of at least 2 weeks after each treatment. Activated T cell cytokine expression (IL-2 & IFN-γ) and percent CD4 + CD25 + FOXP3+ Tregs were evaluated using flow cytometry, both prior to and on the last day of treatment. The difference between pre- and post-treatment values for each group, as well as the difference between treatment groups, was evaluated.Cyclosporine significantly decreased IL-2 and IFN-γ expression when used alone or in combination with low-dose aspirin. High-dose aspirin, but not low-dose aspirin, also significantly decreased IL-2 expression, although the decrease was not as marked as that seen with cyclosporine alone or in combination with aspirin. Neither low-dose nor high-dose aspirin significantly affected IFN-γ expression. No drug or drug combination affected Treg numbers.Low-dose aspirin given with cyclosporine creates the same degree of T-cell cytokine suppression as does cyclosporine alone, suggesting that the two drugs can be used concurrently without significantly altering the immunosuppressive mechanism of action of cyclosporine.

Ticagrelor

Ticagrelor

The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs.

BackgroundCyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets.Hypothesis/ObjectivesOur hypothesis was that the concurrent administration of low‐dose aspirin and cyclosporine would inhibit cyclosporine‐associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis.AnimalsSeven healthy dogs.MethodsA randomized, crossover study utilized turbidimetric aggregometry and a platelet function analyzer to evaluate platelet function during the administration of low‐dose aspirin (1 mg/kg PO q24h), high‐dose aspirin (10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12h), and combined low‐dose aspirin and cyclosporine. The urine 11‐dehydro‐thromboxane‐B2 (11‐dTXB 2)‐to‐creatinine ratio also was determined.ResultsOn days 3 and 7 of administration, there was no difference in the aggregometry amplitude or the platelet function analyzer closure time between the low‐dose aspirin group and the combined low‐dose aspirin and cyclosporine group. On day 7, there was a significant difference in amplitude and closure time between the cyclosporine group and the combined low‐dose aspirin and cyclosporine group. High‐dose aspirin consistently inhibited platelet function. On both days, there was a significant difference in the urinary 11‐dTXB 2‐to‐creatinine ratio between the cyclosporine group and the combined low‐dose aspirin and cyclosporine group. There was no difference in the urinary 11‐dTXB 2‐to‐creatinine ratio among the low‐dose aspirin, high‐dose aspirin, and combined low‐dose aspirin and cyclosporine groups.Conclusions and Clinical ImportanceLow‐dose aspirin inhibits cyclosporine‐induced thromboxane synthesis, and concurrent use of these medications does not alter the antiplatelet effects of aspirin.

Low-dose aspirin plus low-molecular-weight heparin for the prevention of pre-eclampsia: yes, no or maybe.

Low-dose aspirin plus low-molecular-weight heparin for the prevention of pre-eclampsia: yes, no or maybe.

Celecoxib interferes to a limited extent with aspirin-mediated inhibition of platelets aggregation.

The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX-1 binding and its consequences on the aspirin-mediated antiplatelet effects. We investigated ex vivo the interaction between celecoxib and aspirin for COX-1 binding and measured the resulting antiplatelet effects. We applied mechanism-based pharmacokinetic-pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. The predictions of the PK-PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200mgday(-1) celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX-1 binding. Interaction between low dose aspirin and other COX-2 inhibitors and its clinical consequences requires further investigation.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Sturge-weber syndrome.

We try to see the babies prior to the onset of symptoms so that their parents can receive anticipatory guidance regarding seizures and how to recognize and respond to them and so that proper referrals to ophthalmology can be made. If there is any concern on history, exam, or EEG then we obtain a magnetic resonance imaging (MRI) with contrast. If presymptomatic diagnosis of brain involvement is made then treatment with low-dose aspirin is offered and if the brain involvement is extensively bilateral then an anticonvulsant such as levetiracetam is offered as well. Seizures are treated aggressively with a goal of obtaining and maintaining complete seizure suppression as much as possible often with a combination of low-dose aspirin and two anticonvulsants such as levetiracetam and oxcarbazepine. For many patients, this will provide adequate control of their seizures and stroke-like episodes. If the patient fails medical management and seizures are regular and accompanied by plateaued development, significant hemiparesis and visual field deficit and the patient is unilaterally involved and a surgical candidate then surgical management is urged. When the seizures are less regular, little or no hemiparesis or visual field deficit exist, and development is reasonable then this decision is more difficult. For bilaterally involved patients surgery is usually not a good option unless seizures are very severe and mostly coming from one side. Other therapeutic options include the ketogenic/Atkins diet and vagal nerve stimulator although in our experience these usually do not result in cessation of seizures. Endocrine problems occur with increased frequency and must be treated when they are present. The recent discovery of the somatic mutation causing Sturge-Weber syndrome holds promise for new treatment options in the future.

Considerations in antithrombotic therapy among patients undergoing transcatheter aortic valve implantation

Aortic stenosis (AS) accounts for the majority of valvular abnormalities requiring surgical intervention. Platelet dysfunction has been demonstrated among patients with severe aortic stenosis which may predispose patients to bleeding or ischemic events. Surgical aortic valve replacement (AVR) is the standard therapy for severe symptomatic AS; however, a number of patients have very high or prohibitive surgical risk. Transcatheter aortic valve implantation (TAVI) has been shown to be superior to medical therapy among inoperable patients and non-inferior to AVR in patients with high surgical risk. In comparison to AVR, TAVI has been associated with a higher incidence of ischemic cerebrovascular events, conduction abnormalities necessitating permanent pacemaker placement, and vascular complications. Current practice guidelines recommend dual antiplatelet therapy (DAPT) following TAVI using a combination of low dose aspirin and clopidogrel for 3-6months. This regimen may be adjusted in patients with clinical bleeding events or indications for concomitant systemic anticoagulation. Recent and ongoing trials aim to clarify the optimum antithrombotic regimen and duration of therapy following TAVI. Collectively, early studies have not revealed additional benefit of adding clopidogrel to aspirin therapy in regards to reducing ischemic events, but have shown a trend towards increase in major bleeding. TAVI has proven successful, and as its breadth of utility is expanded, further studies are needed to define optimum antithrombotic therapy following TAVI. This article will review the current data for antiplatelet and anticoagulant therapy following TAVI.

Ibudilast, a Phosphodiesterase Inhibitor, in Combination with Low-dose Aspirin Potently Inhibits Guinea Pig Carotid Artery Thrombosis without Extending Bleeding Time and Causing Gastric Mucosal Injury

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis. Each independent use of ASA (300 mg/kg, p.o.) and ibudilast (3 and 10 mg/kg, p.o.) significantly prolonged the TTO, and ASA (300 mg/kg) significantly increased bleeding time (BT) and gastric mucosal injury. A selective PDE4 inhibitor rolipram (1 and 5 mg/kg, p.o.) tended to prolong the TTO without extending BT. ASA (100 mg/kg) plus ibudilast (3 mg/kg) and ASA (100 mg/kg) plus rolipram (5 mg/kg) markedly prolonged the TTO compared with each agent alone. Interestingly, ASA (100 mg/kg) plus ibudilast (3 mg/kg) caused a longer TTO than ASA (300 mg/kg) alone, without significant extension of BT and gastric mucosal injury as observed in ASA (300 mg/kg). These results indicate that the combination of low-dose ASA and ibudilast has a more potent antithrombotic effect than ASA alone without increasing bleeding tendency and gastric mucosal injury. The potent in vivo antithrombotic effect of this combination may be brought about by an action that is associated with PDE4 inhibition of ibudilast.