Mg Of Aspirin Research Articles

Low-dose Aspirin Inhibits Cardiac Sympathetic Activation and Vagal Withdrawal Response to Morning Rising

Aspirin is known to interfere with platelet function and can protect individuals at risk of sudden death. However, this property of aspirin is less defined for cardiac autonomic activity. We assessed pulse rate variability by spectral analysis and measured plasma eicosanoid levels before and after administration of 81-mg aspirin to 12 healthy subjects over a 60-degree head-up tilt test in the morning. In upright posture, low-dose aspirin decreased both the normalized unit value of low-frequency (normalized LF) power (mean ± SD, 82.5 ± 4.5 vs. 77.5 ± 6.5 nu, P = 0.01) and LF/HF ratio (6.0 ± 2.1 vs. 4.7 ± 2.7, P = 0.02) and augmented the normalized unit value of high-frequency power (15.0 ± 4.4 vs. 19.8 ± 6.4 nu, P = 0.004). It simultaneously upregulated plasma 6-keto-PGF1α level (13.4 ± 6.8 vs. 19.7 ± 12.8 pg/mL, P = 0.04) and inhibited plasma thromboxane B2 (TXB2) level (11.6 ± 7.3 vs. 6.3 ± 4.2 pg/mL, P = 0.003). In the upright posture, both before and after aspirin, there was a significant direct correlation between plasma TXB2 levels and the normalized LF power (r = 0.42, P = 0.04) as well as between the plasma TXB2/6-keto-PGF1α ratio and the normalized LF power (r = 0.50, P = 0.01). Administration of low-dose aspirin in healthy people inhibits cardiac sympathetic activation and vagal withdrawal response to morning rising through an alternation of the TXA2/PGI2 balance.

Beneficial Effect of Beraprost Sodium Plus Aspirin in the Treatment of Acute Ischemic Stroke.

BackgroundTo investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS).Material/Methods308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge.ResultsInitially, no significant differences were found between the two groups. After six months, the relapse-free survival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment.ConclusionsIn our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding.

Asymptomatic Large Thrombus Formation in Drug-Eluting Stent 2 Days After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction Patient

A 73-year-old man who smokes presented to the emergency room with inferior ST-segment elevation myocardial infarction. The patient was loaded with 325-mg aspirin and 180-mg ticagrelor, and was immediately taken to the cardiac catheterization laboratory. Coronary angiography (CAG) revealed thrombotic

Effect of Low-Dose Aspirin on Bleeding Following Exodontia: A Prospective Clinical Study

This research aims to study the effects of low-dose aspirin on bleeding after exodontia and to compare statistically and analyze perioperative blood loss during exodontia in patients on aspirin therapy and healthy patients and also to discuss the various measures if required necessary for controlling postoperative bleeding in simple and uncomplicated exodontia. The study included 100 patients, ranging in age from 30 to 60years. The patients were divided into two groups, a test group consisting of 50 patients who were on a daily dose of 75-150mg of aspirin and a control group consisting of 50 patients not on any antiplatelet therapy. All extraction procedures were performed on outpatient basis. Patients were operated under local anesthesia. Post-extraction sockets were checked for bleeding immediately (30min) and followed up at 24, 48, and 72h, and 1week, after the procedure. Amount of intraoperative blood loss was similar in both test and control groups, and there was no excessive postoperative bleeding in any case. Out of 100 patients, only three patients of test group and two patients of control group required level II hemostatic measures and two patients of test group needed level III measures. We could reach a conclusion and recommend that patients on long-term low-dose aspirin (75-150mg) need not to discontinue their aspirin dose prior to routine exodontia and can be carried out safely with enhanced local hemostatic measures, if required.

Safety and Efficacy of a 600-mg Loading Dose of Clopidogrel 24 Hours Before Pipeline Embolization Device Treatment.

Clopidogrel/aspirin antiplatelet therapy routinely is administered 7-10 days before pipeline aneurysm treatment. Our study assessed the safety and efficacy of a 600-mg loading dose of clopidogrel 24 hours before Pipeline Embolization Device (PED) treatment. We performed a retrospective cohort study involving patients treated with pipeline from October 2010 to May 2016. A total of 39.7% (n= 158) of patients were dispensed a loading dose of 650 mg of aspirin plus at least 600 mg of clopidogrel 24 hours preceding PED deployment; 60.3% (n= 240) received 81-325 mg of aspirin daily for 10 days with 75 mg of clopidogrel daily preprocedurally. The mean follow-up was 15.8 months (standard deviation [SD] 12.4 months). modified Rankin Scale (mRS) was registered before the discharge and at each follow-up visit. To control confounding, we used multivariable logistic regression and propensity score conditioning. Of 398 patients, the proportion of female patients was ≈16.5% (41/240) in both groups and shared the same mean of age ≈56.46 years. Similarly, ≈12.2% (mean= 0.09; SD= 0.30) had a subarachnoid hemorrhage. A total of 92% (mean= 0.29; SD= 0.70) from the pretreatment group and 85.7% (mean= 0.44; SD= 0.91) of the bolus group had a mRS ≤2. In a multivariate analysis, bolus did not affect the mRS score, P= 0.24. Seven patients had a long-term recurrence, 2 (0.83%; mean= 0.01; SD= 0.10) from the pretreatment group. In a multivariable logistic regression, bolus was not associated with a long-term recurrence rate (odds ratio [OR] 1.91; 95% confidence interval [CI] 0.27-13.50; P= 0.52) neither with thromboembolic accidents (OR 0.99; 95% CI 0.96-1.03; P= 0.83) nor with hemorrhagic events (OR 1.00; 95% CI 0.97-1.03; P= 0.99). Three patients died: 1 who received a bolus had an acute subarachnoid hemorrhage. The mean mortality rate was parallel in both groups ≈0.25 (SD= 0.16). Bolus was not associated with mortality (OR1.11; 95% CI 0.26-4.65; P= 0.89). The same associations were present in propensity score-adjusted models. In a cohort receiving PED, a 600-mg loading dose of clopidogrel should be safe and efficacious in those off the standard protocol or showing <30% platelet inhibition before treatment.

Prevalence of aspirin resistance in patients with type II diabetes: a descriptive-analytical study .

Aspirin resistance is one of the most important factors for arterial thrombotic events in diabetic patients. This study aimed to evaluate aspirin resistance in diabetic patients. In this cross-sectional study, 180patients who received 80mg of aspirin daily for at least 10 days were studied, and their urinary 11-DH-TXB2 was measured. Those with 11-dehydro-thromboxane B2 above 1,500pg/mg creatinine were considered aspirin resistant. Data with significance level of 5% were analyzed in SPSS-16. The mean±SD of patient age was 60.22±9.59 years and 50% (n=90) were male. BMI was normal in 29.4% of the patients (n=53), the others were overweight or obese. Aspirin resistance was observed in 33 (18%) patients. The relationship between aspirin resistance and gender, age, and BMI was not significant (p>0.05). There is a high prevalence of aspirin resistance in diabetic patients and given that such patients are at risk of arterial thrombotic events, evaluation of aspirin resistance is suggested for those at a high risk of cardiovascular events or recurring events despite the use of aspirin. .

PI3K mutation and effect of aspirin use in breast cancer.

e23209 Background: Increasing literature suggests a protective role of aspirin in breast cancer. PI3K mutation is prevalent in 30% of estrogen receptor positive and 50% of HER2 receptor positive breast cancers. Aspirin inhibits prostaglandin-endoperoxide synthase 2 (PTGS2) through down-regulation of phosphatidylinositol 3-kinase (PI3K). A study in colorectal cancer demonstrated that regular use of aspirin was associated with superior survival among patients with PI3K mutated tumors. The aim of this study was to retrospectively examine the presence of PI3K mutation in breast cancer tissue in patients who used aspirin during treatment, and compare survival between those with and without PI3K mutations. Methods: Among 1259 patients diagnosed with breast cancer between year 2002 to 2013 at Augusta University (AU), 47 patients who used at least 81 mg of aspirin daily during cancer treatment were identified, and their breast cancer tissue blocks were analyzed for PI3K mutation by gene sequencing technique. Genomic DNAs were extracted from formalin fixed paraffin-embedded tissues using GeneRead DNA FFPE kit (Qiagen) and sequenced on Miseq sequencer (Illumina). We selectively analyzed five genes involved in the PI3K pathway, including PIK3CA, AKT, PIK3R1, PTEN, and TP53. The presence of mutation was correlated to overall survival, using Kaplan-Meier and Cox Regression analyses. Results: Of the 47 patients, 53% were Caucasian and 47% were African American. 70% were early stage (TNM stage I, II) and 30% were late stage (TNM stage III, IV). 69% were never smokers, 31% were current or former smokers. ER, PR and HER2 were expressed in 84%, 79%, and 86% patients respectively. 66% had PI3K mutation, and 34% were PI3K wild type. There was no significant difference (log-rank test p = 0.28) in overall survival (OS) of patients with PI3K mutation versus those without, although the former group had longer survival numerically. The multivariable-adjusted hazard ratio (HR) for PI3K mutation was 0.53 (p = 0.29). Conclusions: Our project supports justification for a larger study to explore the role of aspirin in prevention, treatment and prognosis of breast cancer, and to validate biomarkers such as PI3K and related genes mediating the aspirin effect.

MP68-10 PERIOPERATIVE ASPIRIN USE DURING PERCUTANEOUS NEPHROLITHOTOMY (PCNL): OUR SINGLE CENTER EXPERIENCE.

You have accessJournal of UrologyStone Disease: Surgical Therapy VI1 Apr 2017MP68-10 PERIOPERATIVE ASPIRIN USE DURING PERCUTANEOUS NEPHROLITHOTOMY (PCNL): OUR SINGLE CENTER EXPERIENCE. Joshua Ebel and Bodo Knudsen Joshua EbelJoshua Ebel More articles by this author and Bodo KnudsenBodo Knudsen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2326AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The rates of heart disease and nephrolithiasis continue to increase in the United States. As more patients on aspirin for secondary prevention present with large kidney stones, urologists are increasingly faced with the decision to proceed with the less effective but lower risk ureteroscopy or the higher risk but more effective percutaneous nephrolithotomy (PCNL). Leavitt, Smith, and Okeke recently published their experience performing PCNLs on seventeen patients continued on aspirin perioperatively and concluded that the procedure was safe. We wish to add our center's experience to this body of knowledge. METHODS We retrospectively reviewed our single center, single surgeon, experience of 199 PCNLs performed between January 2013 and September 2016. Hemoglobin pre- and post-operatively was recorded as were the relevant related variables of age, sex, BMI, operative duration, skin-to-stone distance, stone size, aspirin dose, aspirin indication, number of blood transfusions, and Clavien-Dindo complication classification. Correlations between hemoglobin and explanatory variables were then explored with linear regression and the Wilcoxon rank-sum test. RESULTS Of the 199 PCNLs performed at our institution in the range of our study, 27 procedures on 23 patients were conducted without discontinuing aspirin perioperatively. Coronary artery disease was the most common indication for aspirin use. In 24 cases, the patient was on 81 mg of aspirin perioperatively with the remaining three patients on 325 mg of aspirin daily. The average patient experienced a 1.3 g/dl drop in hemoglobin perioperatively. The largest drop was 4.1 g/dl, but the lowest post-operative hemoglobin was 8.2 g/dl. No significant associations were found between hemoglobin decline and age, sex, BMI, operative duration, skin-to-stone distance, or stone size. There were no Clavien-Dindo grade III or higher complications in the course of our review, and no patients required a blood transfusion or embolization. In one case, a patient required a three day inpatient stay following stent removal for continuous bladder irrigation after developing gross hematuria but this resolved spontaneously. CONCLUSIONS In our single center experience, PCNLs performed on patients taking aspirin perioperatively were not associated with the need for blood transfusion nor the occurrence of high-grade complications. It is our experience that this practice is safe when performed by expert hands. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e921-e922 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Joshua Ebel More articles by this author Bodo Knudsen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD30-04 PERIOPERATIVE MANAGEMENT OF LOW-DOSE ASPIRIN IN SURGICAL KIDNEY STONE MANAGEMENT: A SURVEY OF CURRENT ENDOUROLOGIC PRACTICE PATTERNS.

You have accessJournal of UrologyStone Disease: Surgical Therapy III1 Apr 2017PD30-04 PERIOPERATIVE MANAGEMENT OF LOW-DOSE ASPIRIN IN SURGICAL KIDNEY STONE MANAGEMENT: A SURVEY OF CURRENT ENDOUROLOGIC PRACTICE PATTERNS. Joshua Ebel, Brian Eisner, Michael Lipkin, Ben Chew, and Bodo Knudsen Joshua EbelJoshua Ebel More articles by this author , Brian EisnerBrian Eisner More articles by this author , Michael LipkinMichael Lipkin More articles by this author , Ben ChewBen Chew More articles by this author , and Bodo KnudsenBodo Knudsen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1369AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The recently published American Urological Association guidelines on the surgical management of kidney stones state that ureteroscopy (URS) is the preferred treatment for patients on continuous antiplatelet regimens, however multiple recent case series questioned whether continuing low-dose aspirin at the time of percutaneous nephrolithotomy (PCNL) or extracorporeal shockwave lithotripsy (ESWL) could be safe in certain settings. We conducted a survey study to further define current practice trends and guide future research into the topic. METHODS An electronic survey was sent to approximately 2000 members of the Endourology Society in September of 2016. 184 substantive responses (9.2%) were received from members in six continents. The resulting data was analyzed and associations were measured by Pearson's chi-squared test. RESULTS 63% of respondents were fellowship trained, 67% practiced in academic centers, and 70% practiced in North America or Europe. 79% of respondents stated that they routinely performed URS on patients taking 81 mg of Aspirin (ASA) daily as opposed to only 29% when asked the same question with regard to PCNL (Odds Ratio (OR): 17.4, p < 0.001) and 18% with regard to ESWL (OR: 9.2, p < 0.001). Those in academic practice were more likely to perform PCNL (OR: 2.4, p = 0.02) but not ESWL (p = 0.51) on patients while taking ASA. Respondents from outside North America or Europe rarely reported performing PCNL or ESWL on patients taking ASA (40% vs. 5%, p <0.001 and 22% vs 7%, p = 0.01). Neither fellowship training nor high case volumes were associated with an increased likelihood of performing PCNL or ESWL in patients taking ASA; however if a surgeon performed fellowship training in North America or Europe, they were significantly more likely to routinely perform PCNL on patients taking ASA (p <.0001). Those who performed PCNL or ESWL on ASA were significantly less likely to consult cardiology regarding cessation of ASA pre-operatively (p <.001). There was a trend toward younger physicians performing PCNL and ESWL on ASA (p = 0.06, 0.05, respectively). CONCLUSIONS Urologists commonly perform URS in patients taking aspirin, but only a minority perform ESWL and PCNL in patients on ASA. There was a wide regional variation in aspirin usage in ESWL. Surgeons in academic centers and with fellowship training from North America or Europe were more likely to perform PCNL on ASA. The next step is to evaluate the safety and outcomes of remaining on ASA for surgery. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e579 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Joshua Ebel More articles by this author Brian Eisner More articles by this author Michael Lipkin More articles by this author Ben Chew More articles by this author Bodo Knudsen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

BackgroundAlthough many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin.MethodsIn this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding.ResultsA total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups.ConclusionsAmong patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439.)

Transfer of Low Dose Aspirin Into Human Milk.

Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

TWO CASES OF ACUTE EPIDURAL HEMATOMA FORMATION AFTER CERVICAL INTERLAMINAR EPIDURAL STEROID INJECTIONS

Cervical interlaminar epidural injections are rarely associated with epidural hematoma resulting in surgical decompression. Multiple strategies in the prevention of epidural hematoma after cervical epidural injections are based on cessation of therapy in patients with bleeding disorders on antiplatelet therapy, fi sh oil, and multiple other drugs. Multiple guidelines from organizations across the globe have recommended continuation of nonsteroidal anti-infl ammatory drugs (NSAIDs) and low dose aspirin. Guidelines also have recommended to continue or cessation of antithrombotic agent therapy based on risk benefi t ratio, due to associated risks of thrombotic events with interventional techniques or other surgeries with discontinuation of antiplatelet therapy. We report 2 cases of cervical epidural hematoma requiring surgical decompression, without residual dysfunction. The fi rst case was in a 41-year-old Caucasian woman with controlled hypertension; however, with no drug therapy contributing to bleeding and 2 uneventful cervical interlaminar epidural injections, the patient developed a cervical epidural hematoma after the third procedure which was performed uneventfully. She developed rapid paralysis and underwent surgical decompression without residual dysfunction. The second case involved a cervical epidural injection resulting in a cervical epidural hematoma. This patient was on 81 mg of aspirin and was continued with therapy. Surgical decompression was carried out with no residual dysfunction. This patient also received Toradol for pain control in the recovery room which may have exacerbated the epidural hematoma. These 2 case reports illustrate that cervical epidural hematoma is a rare, but fatal occurrence associated with cervical epidural injections. Appropriate patient selection with constant vigilance on post operative course and follow-up treatment with surgical intervention or conservative management is crucial. It is also crucial to understand the role of loss of resistance technique with air only which may complicate the closed space phenomenon of cord compression and post procedure pain at the injection site which is different from the pain ever experienced by the patient with the previous injections. Key words: Interventional techniques, cervical epidural injections, cervical epidural hematoma, bleeding disorders, aspirin, antithrombotic agents, Ketoralac

Abstract TP412: Predicting Pharmacokinetic versus Pharmacodynamic Aspirin Resistance in Patients

20%-40% of patients being treated with aspirin for secondary prophylaxis of stroke or myocardial infarction may derive no antiplatelet effects. Early identification of patients as pharmacokinetically or pharmacodynamically resistant to aspirin has the potential to become an invaluable clinical tool, reducing delays to optimal treatment, cardiovascular events, and healthcare costs. This study tested the capability of an assay that was previously developed in healthy volunteers, to differentiate between these two types of resistance in patients. Patients who needed aspirin treatment in the course of normal medical care were included. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to a maximum 325 mg daily occurred every 10-14 days based on the results of whole blood impedance aggregation testing to the agonists, collagen (1 ug/mL, 5 ug/mL) and arachidonate (0.5 mM). The in vitro test was conducted in triplicate by performing the same aggregometry test on blood samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Resistance was defined as a response to collagen 1 ug/mL &gt;10 ohms, and/or response to arachidonate &gt;6 ohms, and/or the ratio of collagen 1 to 5 ug/mL &gt;0.5. Patients were excluded if they had any disorders affecting platelet function, an abnormal CBC, alcohol use within 24 hours of a test, NSAID use, or had any conditions that would affect absorption. Of the 36 patients included who were compliant with their 81 mg aspirin regimen based on pill count, 16 were found to be resistant to 81 mg of aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten actually remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose of aspirin while six actually did. No statistical difference was found between predicted aspirin response and actual aspirin response (p=0.61). Sensitivity was 83% and specificity was 80%. In conclusion, results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin therapy necessitating an alternative antiplatelet regimen. Larger, multi-site studies are inevitably needed.

Low-Dose Aspirin Is Effective Chemoprophylaxis Against Clinically Important Venous Thromboembolism Following Total Joint Arthroplasty

Aspirin is a safe and effective prophylaxis for the prevention of venous thromboembolism following total joint arthroplasty. The optimal dose of aspirin prophylaxis is unknown. Our hypothesis was that lower-dose aspirin is as effective as higher-dose aspirin for the prevention of venous thromboembolism and is associated with fewer gastrointestinal side effects. In a prospective, crossover study, we analyzed 4,651 primary total joint arthroplasty cases performed from July 2013 to June 2015. For 4 weeks, 3,192 patients received enteric-coated 325-mg aspirin twice daily (the 325-mg aspirin group) and 1,459 patients received 81-mg aspirin twice daily (the 81-mg aspirin group). There were no significant differences (p > 0.05) in sex, body mass index, or Charlson Comorbidity Index between the two patient populations. Recorded complications occurring within 90 days postoperatively included symptomatic venous thromboembolism (deep venous thrombosis and pulmonary embolism), gastrointestinal complications, acute periprosthetic joint infection, and death. The incidence of venous thromboembolism of 0.1% (95% confidence interval [CI], 0% to 0.3%) in the 81-mg aspirin group (1 with deep venous thrombosis and 1 with pulmonary embolism) was not significantly different (p = 0.345) from 0.3% (95% CI, 0.1% to 0.6%) in the 325-mg aspirin group (7 with deep venous thrombosis and 5 with pulmonary embolism). The incidence of gastrointestinal bleeding or ulceration of 0.3% (95% CI, 0% to 0.5%) in the 81-mg aspirin group was slightly, but not significantly (p = 0.66), lower than the 0.4% (95% CI, 0.2% to 0.6%) in the 325-mg aspirin group. The incidence of acute periprosthetic joint infection was 0.2% (95% CI, 0% to 0.4%) in the 81-mg aspirin group compared with 0.5% (95% CI, 0.2% to 0.7%) in the 325-mg aspirin group (p = 0.28). The 90-day mortality rate was similar in both groups at 0.1% (95% CI, 0% to 0.2%) in the 81-mg aspirin group and 0.1% (95% CI, 0% to 0.2%) in the 325-mg aspirin group (p = 0.78). Our study demonstrates that low-dose aspirin is not inferior to high-dose aspirin for venous thromboembolism prophylaxis following total joint arthroplasty. This is not unexpected, as the available literature demonstrates that low-dose aspirin is as effective as higher-dose aspirin in the prevention of acute coronary syndrome and cerebrovascular events. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus

BackgroundA limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. ObjectivesThe goal of this study was to determine if oral bioavailability mediates nonresponsiveness. MethodsThe rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B2 (TXB2) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB2 associated with elevated thrombotic risk (<99.0% inhibition or TXB2 >3.1 ng/ml) within 72 h after 3 daily aspirin doses. ResultsThe rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin–treated subjects had serum TXB2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [Cmax] and 77% and 82% lower AUC0–t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB2, with marked interindividual variability. ConclusionsA high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB2 generation due to incomplete absorption. Reduced bioavailability may contribute to “aspirin resistance” in patients with diabetes. (Pharmacodynamic Evaluation of PL2200 Versus Enteric-Coated and Immediate Release Aspirin in Diabetic Patients; NCT01515657)

Attenuation of the Effect of 100 mg Aspirin on Platelet Aggregation in Regular Kava Drinkers

Background and Purpose: Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several others may have serious clinical consequences. Kava (Piper methysticum) is an ancient crop of the western Pacific. Kava preparation and extracts are very popular in the Pacific and the potential remains for herbal supplements like kava to interact negatively with other drugs like aspirin in vivo which needs to be thoroughly explored. Management of cardiovascular disease in Fiji includes anti-platelet drugs, especially aspirin which is prescribed routinely. Aim: Our study aimed to assess the effect of two different doses of aspirin (100 mg and 300 mg) on the degree of platelet aggregation induced by collagen amongst healthy non kava drinkers and kava drinkers. The objective of this study was to examine potential effect of concomitant aspirin on platelet aggregation (PA) in kava drinkers. Methods: Platelet aggregation was measured using whole blood platelet aggregometer (Chronology Corp) using collagen as an aggregating agent in two main ethnic groups, Fijians and Indo-Fijians, before and after the intake of a single dose of 100 mg and 300 mg of aspirin. The Fijian and Indo-Fijian volunteers were divided into three groups, non-kava drinkers (NKD), occasional-kava drinkers (OKD) and regular-kava drinkers (RKD). Results: The results were found to be non-significant in NKD, OKD and RKD Fijians and IndoFijians before aspirin intervention, the intake of kava did not have any effect on platelet aggregation. Overall PA remained within the normal range (15-27 Ω). After a single dose of 100 mg of aspirin, a large number of participants in both ethnic groups of RKD were found to have decreased aspirin sensitivity. The decreased aspirin sensitive participants had their PA within the normal range (15-27 Ω) even after administration of aspirin. All the participants showed a reduction in PA ( 0.05). The most important finding of this study is that 100 mg aspirin had significantly less inhibitory effect on PA in both Fijian and Indo-Fijian RKD (p < 0.001). Conclusion: Our studies show a reduced effect of aspirin on platelet aggregation in regular kava drinkers (RKD).

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization

BackgroundThe frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. ObjectiveTo determine the rate and type of reaction at 325 mg of aspirin during desensitization. MethodsA retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20–40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. ResultsEighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0–10.3; P = .05). ConclusionDuring aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home.

Antiplatelet Therapy Combinations and Thrombogenicity in Patients with Non-Valvular Atrial Fibrillation.

Background and ObjectivesCombination antiplatelet therapy reduces the risk of ischemic stroke compared with aspirin monotherapy in non-valvular atrial fibrillation (NVAF) patients. The underlying mechanism, however, remains unclear. In addition, the association between platelet inhibition and thrombogenicity in NVAF has not been evaluated.Subjects and MethodsWe randomized 60 patients with NVAF that were taking 100 mg of aspirin daily (>1 month) to adding 75 mg of clopidogrel daily (CLPD group), 100 mg of cilostazol twice daily (CILO group), or 1000 mg of omega-3 polyunsaturated fatty acid twice daily (PUFA group). Biomarkers (von Willebrand factor antigen [vWF:Ag], fibrinogen, D-dimer, and high-sensitivity C-reactive protein [hs-CRP]) and platelet reactivity (PR), which were the levels stimulated by adenosine diphosphate (ADP), thrombin-receptor agonist peptide, collagen, and arachidonic acid, were measured at baseline and 30-day follow-up.ResultsCombination antiplatelet therapy significantly reduced vWF:Ag and fibrinogen levels (7.7 IU/dL, p=0.015 and 15.7 mg/dL, p=0.005, respectively), but no changes were found in D-dimer and hs-CRP levels. The CLPD and CILO groups showed fibrinogen and vWF:Ag level reductions (24.9 mg/dL, p=0.015 and 9.3 IU/dL, p=0.044, respectively), whereas the PUFA group did not show any differences in biomarkers. Irrespective of regimen, the changes in fibrinogen and vWF:Ag levels were mainly associated with the change in ADP-mediated PR (r=0.339, p=0.008 and r=0.322, p=0.012, respectively).ConclusionIn patients with NVAF, combination antiplatelet therapy showed reductions for vWF:Ag and fibrinogen levels, which may be associated with the inhibitory levels of ADP-mediated PR. The clinical implications of these findings need to be evaluated in future trials.

Effects of Aspirin Therapy on Ultrasound–Guided Renal Allograft Biopsy Bleeding Complications

PurposeTo determine if patient aspirin exposure and timing affect bleeding risk after renal allograft biopsy. Materials and MethodsReview of 6,700 renal allograft biopsies (in 2,362 unique patients) was performed. Median patient age was 53.0 years [interquartile range 43.0, 62.0]; 56.2% of patients were male. Of biopsies, 4,706 (70.2%) were performed in patients with no aspirin exposure within 10 days of biopsy; 664 (9.9%), were performed within 8–10 days of aspirin exposure; 855 (12.8%), within 4–7 days; and 475 (7.1%), within 0–3 days. Follow-up to 3 months after the procedure was completed in all patients. Biopsies were categorized as protocol or indication; 19.7% were indication biopsies. Bleeding complications were graded based on SIR criteria. Logistic regression models examined the association between aspirin use and bleeding events. ResultsRate [95% confidence interval] of major bleeding complications was 0.24% [0.14, 0.39], and rate of any bleeding complication was 0.66% [0.46, 0.90]. Bleeding events were significantly associated with patients undergoing indication biopsies compared with protocol biopsies (odds ratio [OR] 2.27, P = .012). Patient factors associated with major bleeding complications in multivariate models included estimated glomerular filtration rate (OR 0.61, P = .016) and platelet count (OR 0.64, P = .033). Aspirin use was not significantly associated with increased risk of bleeding complication except for use of 325 mg of aspirin within 3 days of biopsy (any complication OR 3.87 [1.12, 13.4], P = .032; major complication OR 6.30 [1.27, 31.3], P = .024). ConclusionsRenal allograft biopsy bleeding complications are very rare, particularly for protocol biopsies. Use of 325 mg of aspirin within 3 days of renal allograft biopsy was associated with increased bleeding complications.

Aspirin for in vitro fertilisation.

Aspirin is used with the aim of optimising the chance of live birth in women undergoing assisted reproductive technology (ART), despite inconsistent evidence of its efficacy and safety (in terms of intraoperative bleeding during oocyte retrieval and risk of miscarriage). The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is the second update of the review first published in 2007. To evaluate the effectiveness and safety of aspirin in women undergoing ART. We searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4) in the Cochrane Library (searched 9 May 2016); the databases MEDLINE (1946 to 9 May 2016) and Embase (1974 to 9 May 2016); and trial registers (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform search portal). We also examined the reference lists of all known primary studies and review articles, citation lists of relevant publications and abstracts of major scientific meetings, combined with the Cochrane Gynaecology and Fertility Group's search strategy. Randomised controlled trials on aspirin for women undergoing ART. Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcome was live birth. Secondary outcomes included clinical pregnancy, ongoing pregnancy, multiple pregnancy, miscarriage, and other complications associated with IVF/ICSI or with pregnancy and birth. We combined data to calculate risk ratios (RRs) (for dichotomous data) and mean differences (MDs) (for continuous data) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. The search identified 13 trials as eligible for inclusion in the review, including a total of 2653 participants with a mean age of 35 years. Ten studies used a dose of 100 mg and three used 80 mg of aspirin per day. In most of them, aspirin was commenced immediately at the start of down-regulation, while the duration of treatment varied widely. Eight studies provided a placebo for the control group.There was no evidence of a difference between the aspirin group and the group receiving no treatment or placebo in rates of live birth (RR 0.91, 95% CI 0.72 to 1.15, 3 RCTs, n = 1053, I² = 15%, moderate-quality evidence). In addition, clinical pregnancy rates were also similar for the two groups (RR 1.03, 95% CI 0.91 to 1.17, 10 RCTs, n = 2142, I² = 27%, moderate-quality evidence); sensitivity analysis, excluding studies at high risk of bias, did not change the effect estimate. There was no evidence of a difference between groups in terms of multiple pregnancy as confirmed by ultrasound (RR 0.67, 95% CI 0.37 to 1.25, 2 RCTs, n = 656, I² = 0%, low-quality evidence), miscarriage (RR 1.10, 95% CI 0.68 to 1.77, 5 RCTs, n = 1497, I² = 0%, low-quality evidence), ectopic pregnancy (RR 1.86, 95% CI 0.75 to 4.63, 3 RCTs, n = 1135, I² = 0%, very low quality evidence) or vaginal bleeding (RR 1.01, 95% CI 0.14 to 7.13, 1 RCT, n = 487, very low quality evidence). Data were lacking on other adverse effects.The overall quality of the evidence ranged from very low to moderate; limitations were poor reporting of study methods and suspected publication bias. Currently there is no evidence in favour of routine use of aspirin in order to improve pregnancy rates for a general IVF population. This is based on available data from randomised controlled trials, where there is currently no evidence of an effect of aspirin on women undergoing ART, as there is no single outcome measure demonstrating a benefit with its use. Furthermore, current evidence does not exclude the possibility of adverse effects.