Daily Aspirin Therapy Research Articles

Fixed dose combination of aspirin and pantoprazole: Results of a multicenter, comparative, randomized, double-blind, double dummy, phase III study in Indian patients

ObjectiveTo compare the efficacy and safety of a fixed-dose combination of aspirin and pantoprazole with that of aspirin alone for the prevention of gastro duodenal mucosal damage in patients taking aspirin for secondary prevention of cardiovascular disease or cerebrovascular disease. MethodsThis was a comparative, double-blind, double-dummy, randomized, multicenter, phase III study conducted in patients taking aspirin ≤150 mg daily for ≥3 to ≤6 months and expected to require daily aspirin therapy for at least 6 months for the secondary prevention of cardiovascular disease or cerebrovascular disease. ResultsA total of 240 patients were randomized to receive either a fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg or aspirin 150 mg alone in a 2:1 ratio. The proportion of non-responders (patients experiencing gastroduodenal events) was 9.7 % in the test group (fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg) compared to 19.7 % in the comparator group (aspirin 150 mg) at week 12, while the proportions were 11.0 % in the test group and 22.4 % in the comparator group at the end of 24 weeks of treatment (p-value was <0.05 at week 12 and 24). GI injuries were significantly less in test group as compared to comparator group. Both drugs were well tolerated by all patients. ConclusionThe fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg was found to be more efficacious and safer compared to aspirin 150 mg alone for the prevention of gastroduodenal mucosal damage in patients receiving aspirin.

Association between daily aspirin therapy and risk of hepatocellular carcinoma according to metabolic risk factor burden in non-cirrhotic patients with chronic hepatitis B.

Several studies have demonstrated chemopreventive effects of aspirin against hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). To investigate the associations of aspirin use with risks of HCC, liver-related mortality, and major bleeding according to metabolic risk factor burden among non-cirrhotic patients with CHB METHODS: Using the Korean National Health Insurance Service database, we identified 282,611 non-cirrhotic adults with CHB. Data on obesity, diabetes, high blood pressure, and hypercholesterolemia were collected. Subjects were stratified into lower and higher metabolic risk groups (≤2 and ≥3 risk factors, respectively). Propensity score-matched cohorts of aspirin users and non-users were generated. Risks of HCC, liver-related death and major bleeding were analyzed. During the median follow-up of 7.4 years, positive associations between metabolic risk factor burden and outcomes were verified (all ptrend < 0.001). In the lower metabolic risk group (13,104 pairs), the association between aspirin use and HCC risk was not significant after multivariable adjustment (adjusted subdistribution hazard ratio [aSHR]: 0.93; 95% CI: 0.84-1.03); however, aspirin use was associated with elevated major bleeding risk (aSHR: 1.22; 95% CI: 1.08-1.39). In the higher metabolic risk group (2984 pairs), aspirin use was associated with reduced risks of HCC (aSHR: 0.72; 95% CI: 0.57-0.91) and liver-related mortality (aSHR: 0.69; 95% CI: 0.50-0.96) without an increase in risk of major bleeding (aSHR: 1.02; 95% CI: 0.79-1.32). Aspirin therapy was associated with reduced risks of HCC and liver-related death without excess risk of major bleeding, in non-cirrhotic patients with CHB who had a higher metabolic risk factor burden.

TO CHALLENGE OR AVOID? POSSIBLE ASPIRIN ALLERGY IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA

<h3>Introduction</h3> Aspirin remains an important component of dual antiplatelet therapy following percutaneous coronary intervention (PCI). Despite studies showing safety in discontinuing aspirin post PCI through use of P2Y12 inhibitor therapy plus anticoagulation, no large, randomized trials evaluate an initial aspirin-free regimen post PCI without systemic anticoagulation. Aspirin intolerances occur in 20% of patients, with only 2% being true allergies. Most aspirin intolerances are linked to asthma, rhinitis, and chronic idiopathic urticaria (CIU). Differentiating this population is important for optimizing care. <h3>Case Description</h3> C.P. is a 54-year-old male with CIU referred for evaluation of aspirin allergy prior to coronary angiography with possible PCI. In 2001, C.P. developed right periorbital edema an hour after his third dose of daily aspirin therapy. Antihistamines reduced the swelling within hours, however due to reaction, his physician recommended discontinuing aspirin. He noted taking aspirin as a child and ibuprofen as an adult without incident. An in-clinic open oral drug challenge to aspirin was conducted. The patient was given 1/10^th of the full dose, followed by the remaining dose then monitored for 1 hour. The patient was diagnosed with NSAID exacerbated CIU and discharged with aspirin and antihistamines for control. <h3>Discussion</h3> Without clear guidelines for managing NSAID induced CIU, many physicians recommend avoidance, resulting in suboptimal care. 20-40% of CIU patients have flares triggered by NSAIDs, and many are misdiagnosed with an aspirin allergy. Our case demonstrates that through careful history and oral challenge, aspirin exacerbated CIU can be effectively managed without forgoing quality care.

Atypical Presentation of Traumatic Pediatric Carotid Artery Dissection: A Case Report.

IntroductionCarotid artery dissection is a rare but serious condition manifesting with signs and symptoms that closely overlap with other more benign medical diagnoses. This vascular injury, however, can result in debilitating sequelae, including thromboembolic cerebrovascular accidents.Case ReportWe describe the atypical presentation of a healthy eight-year-old male who presented to the emergency department (ED) with generalized abdominal pain and non-bloody, non-bilious emesis. These symptoms occurred nine days after he sustained blunt head trauma after a non-syncopal fall from standing while playing hockey. He was initially diagnosed with gastroesophageal reflux disease and constipation and was discharged home. The following day he developed an acute headache followed shortly by gait ataxia, prompting a return visit to the ED. Imaging of the head and neck revealed a left internal carotid artery dissection. The patient was started on intravenous unfractionated heparin and admitted to the hospital. He was later discharged symptom-free on therapeutic enoxaparin for eight weeks, followed by daily aspirin therapy.ConclusionPediatric trauma patients, especially those sustaining insult to the head and cervical spine, are at risk for craniocervical arterial injuries. This rare but dangerous pathology often manifests in a non-specific, delayed fashion making it a challenging diagnosis for physicians to make on the initial medical encounter.1,2 Maintaining a high clinical suspicion for carotid artery dissection is required to make this diagnosis and should guide a thorough history, physical examination, and appropriate imaging in order to improve patient morbidity and mortality. This case emphasizes key clinical features and risk factors of this disease that may help emergency clinicians promptly recognize and treat this entity.

Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital

Study objectiveThis study describes a pharmacist-led process to identify and discontinue inappropriate aspirin in patients receiving concomitant anticoagulant therapy and to evaluate the effectiveness of the intervention. SettingThe study took place in an outpatient anticoagulation clinic within a small community hospital. ParticipantsPatients ≥40 years old on indefinite anticoagulation therapy for atrial fibrillation and/or venous thromboembolism were included. DesignThis is a quality improvement initiative. InterventionsUtilizing the electronic medical record and patient interview, use and indication for daily aspirin therapy was confirmed. Prospectively collected patient demographics and past medical history were used to determine appropriateness of aspirin therapy. For patients identified as receiving inappropriate aspirin therapy, a fax was sent to the referring provider recommending aspirin discontinuation. Main outcome measuresTo assess the effectiveness of the intervention, outcomes were retrospectively measured. The primary outcome was the percentage of “accepted” recommendations. Secondary outcomes included the prevalence, dosing, and indications for aspirin therapy. ResultsEighty (33 %) of 242 patients were on aspirin. Fifty-two patients with atrial fibrillation and/or venous thromboembolism were assessed and aspirin was deemed inappropriate in 22 patients. The provider agreed with deprescribing aspirin therapy in 45 %. The most common dose and indication of aspirin therapy was 81 mg (98 %) and primary prevention (40 %) respectively. ConclusionsIn our small practice, pharmacist-led interventions were an effective means to recommend aspirin discontinuation in our identified patients. Further studies are needed to optimize a pharmacist's role and address the long-term effects of deprescription.

Aspirin challenge and desensitization in patients with suspected AERD in Qatar.

Background: Aspirin-exacerbated respiratory disease (AERD) is a chronic disease characterized by chronic rhinosinusitis, nasal polyposis, asthma, and intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin challenge is considered the gold standard for diagnosing AERD. Many patients with AERD have reported clinical benefits when desensitized to aspirin and maintained on daily aspirin therapy. In this study, we have summarized aspirin challenges and aspirin desensitization in our division during the past ten years.Methods: We reviewed aspirin challenges and desensitization procedures performed in the Allergy and Immunology Division at the Hamad Medical Corporation, Doha, Qatar, between 2010 and 2020 from our procedures log registry and reported the results of the procedures.Results: The procedures were performed for patients with chronic rhinosinusitis, nasal polyposis, and bronchial asthma with a historical reaction to NSAIDs or those never exposed to NSAIDs. The challenge and desensitization procedure protocol is outlined in table.1. Of the 45 procedures performed, 36 (80%) patients reacted during aspirin desensitization; and their characteristics, historical reaction to NSAIDs, provoking dose, length of desensitization, and types of reactions were reviewed. Of the reactors, 32 (88%) patients completed aspirin desensitization successfully. The mean ( ± SD) age of patients was 46 ( ± 11.6) years, and 51% were women. The historical symptoms were asthma symptoms (56%) and naso-ocular (21%). The common (71%) reaction during the procedure was asthma symptoms, and 29% had naso-ocular symptoms. The provoking dose was 50–75 mg in most patients. The desensitization procedure was carried out over 2 days in most patients; however, 29% of the patients needed more than 2 days to complete the desensitization. None of the reactors needed emergency epinephrine use or hospital admission.Conclusion: In our review, desensitization was successful in all the patients who reacted to aspirin, and it was the only therapeutic choice for patients with AERD before the era of biologics. The procedure was well tolerated in most patients. Aspirin challenge was positive in 80% of our patients with suspected AERD, and this has an important diagnostic value that may help in choosing the proper biologic, such as dupilumab, for these patients.

Influence of daily aspirin therapy on ACE2 expression and function—implications for SARS‐CoV‐2 and patients with aspirin‐exacerbated respiratory disease

In March 2020, the French Minister of Health warned against the use of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen, suggesting that their use might be associated with more severe disease presentation in patients with COVID-19.1 This advice was apparently based on unpublished anecdotal reports that patients who had been exposed to NSAIDs developed more severe symptoms of COVID-19.

The role of aspirin desensitization followed by oral aspirin therapy in managing patients with aspirin-exacerbated respiratory disease: A Work Group Report from the Rhinitis, Rhinosinusitis and Ocular Allergy Committee of the American Academy of Allergy, Asthma & Immunology

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the cycloxgenase-1 enzyme. Patients with AERD on average have more severe respiratory disease compared with patients with chronic rhinosinusitis with nasal polyps and/or asthma alone. Although patients with AERD traditionally develop significant upper and lower respiratory tract symptoms on ingestion of cycloxgenase-1 inhibitors, most of these same patients report clinical benefit when desensitized to aspirin and maintained on daily aspirin therapy. This Work Group Report provides a comprehensive review of aspirin challenges, aspirin desensitizations, and maintenance aspirin therapy in patients with AERD. Identification of appropriate candidates, indications and contraindications, medical and surgical optimization strategies, protocols, medical management during the desensitization, and recommendations for maintenance aspirin therapy following desensitization are reviewed. Also included is a summary of studies evaluating the clinical efficacy of aspirin therapy after desensitization as well as a discussion on the possible cellular and molecular mechanisms explaining howthis therapy provides unique benefit to patients with AERD.

Mepolizumab does not prevent all aspirin-induced reactions in patients with aspirin-exacerbated respiratory disease: A case series

Aspirin-exacerbated respiratory disease (AERD) is a syndrome that includes nasal polyposis, asthma, and nonsteroidal anti-inflammatory drug sensitivity. This clinical triad is seen in about 7% of adults with asthma, and in about 15% of those with severe asthma,1 with the average age of onset being 34 years. A positive aspirin-induced reaction during a provocative aspirin challenge is the current standard for confirmative diagnosis.2 Aspirin desensitization, followed by initiation of daily high-dose aspirin therapy, is often used to help reduce nasal polyposis and asthma symptoms in these patients.

Influence of Sex on Platelet Reactivity in Response to Aspirin.

BackgroundThere are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood.Methods and ResultsHealthy volunteers (n=378 208 women) and patients with coronary artery disease or coronary artery disease risk factors (n=217 112 women) took aspirin for 4 weeks. Light transmittance aggregometry using platelet‐rich plasma was used to measure platelet reactivity in response to epinephrine, collagen, and ADP at baseline, 3 hours after the first aspirin dose, and after 4 weeks of daily aspirin therapy. A subset of patients underwent pharmacokinetic and pharmacodynamic assessment with levels of salicylate and cyclooxygenase‐1–derived prostaglandin metabolites and light transmittance aggregometry in response to arachidonic acid and after ex vivo exposure to aspirin. At baseline, women had increased platelet aggregation in response to ADP and collagen. Innate platelet response to aspirin, assessed with ex vivo aspirin exposure of baseline platelets, did not differ by sex. Three hours after the first oral aspirin dose, platelet aggregation was inhibited in women to a greater degree in response to epinephrine and to a lesser degree with collagen. After 4 weeks of daily therapy, despite higher salicylate concentrations and greater cyclooxygenase‐1 inhibition, women exhibited an attenuation of platelet inhibition in response to epinephrine and ADP.ConclusionsWe observed agonist‐dependent sex differences in platelet responses to aspirin. Despite higher cyclooxygenase‐1 inhibition, daily aspirin exposure resulted in a paradoxical attenuation of platelet inhibition in response to epinephrine and ADP over time in women but not in men.

Association of Daily Aspirin Therapy With Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis C Virus Infection

Aspirin therapy has been associated with reduced risk of colon cancer, but there is only limited evidence for its effects on risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We aimed to investigate the association of daily aspirin therapy with HCV-related HCC risk. In this cohort study, based on Taiwan's National Health Insurance Research Database, we screened 237,963 patients with chronic HCV infection for the period of 1997 through 2011. We excluded patients with confounding conditions and 2478 patients who continuously received daily aspirin therapy for 90 days or more (treated group) were randomly matched 1:2 with 4956 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores. Cumulative incidence of, and hazard ratio (HR) for, HCC development were analyzed after we adjusted for patient mortality as a competing risk event. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group over 5 years (4.67%; 95% CI, 3.74%-5.59% vs 7.32%; 95% CI, 6.33%-8.30%; P<.001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.78, 95% CI, 0.64-0.95; P = .011), after adjustment for age per year, male sex, cirrhosis, liver decompensation, hyperlipidemia, statin use, and interferon therapy. Sensitivity subgroup analyses also verified this association (all HRs<1.0). In addition, older age (HR, 1.03 per year; 95% CI, 1.02-1.04), male sex (HR, 1.46; 95% CI, 1.21-1.77), and cirrhosis (HR, 3.13; 95% CI, 2.55-3.84) were independently associated with an increased HCC risk. In a nationwide cohort study in Taiwan, we found aspirin therapy to be significantly associated with a reduced risk of HCV-related HCC.

Unique Effect of Aspirin Therapy on Biomarkers in Aspirin-exacerbated Respiratory Disease. A Prospective Trial.

Rationale: Daily high-dose aspirin therapy benefits many patients with aspirin-exacerbated respiratory disease but provides no benefit for aspirin-tolerant patients with asthma. Type 2 inflammation characterizes aspirin-exacerbated respiratory disease.Objectives: To determine whether high-dose aspirin therapy changes biomarkers of type 2 inflammation in aspirin-exacerbated respiratory disease.Methods: Forty-two subjects with aspirin-exacerbated respiratory disease underwent an aspirin desensitization and were placed on high-dose aspirin (1,300 mg daily). Fifteen aspirin-tolerant subjects with asthma were also placed on high-dose aspirin. Biologic specimens and clinical parameters were collected at baseline and after 8 weeks on aspirin. Urinary eicosanoids, plasma tryptase and cytokine levels, platelet-leukocyte aggregates, and granulocyte transcripts were assessed.Measurements and Main Results: Eight weeks of high-dose aspirin decreased nasal symptoms and urinary prostaglandin E metabolite (P < 0.05) and increased urinary leukotriene E4 (P < 0.01) levels in subjects with aspirin-exacerbated respiratory disease, but not in those with aspirin-tolerant asthma. Urinary prostaglandin D2 and thromboxane metabolites decreased in both groups. Only in subjects with aspirin-exacerbated respiratory disease, exhaled nitric oxide (P < 0.05), plasma tryptase (P < 0.01), and blood eosinophil (P < 0.01) and basophil (P < 0.01) counts increased and plasma tryptase correlated with eosinophil counts (Pearson r = 0.514; P < 0.01) on aspirin. After correction for eosinophil counts, aspirin-induced changes in blood granulocyte transcripts did not differ between groups. Aspirin had no effect on platelet-leukocyte aggregates, platelet activation markers, or plasma cytokines in either group.Conclusions: High-dose aspirin therapy for 8 weeks paradoxically increases markers of type 2 inflammation in subjects with aspirin-exacerbated respiratory disease, despite reducing nasal symptoms. This effect of aspirin is unique to aspirin-exacerbated respiratory disease and not observed in subjects with aspirin-tolerant asthma.

Role of and Recent Evidence for Antiplatelet Therapy in Prevention of Cardiovascular Disease in Diabetes

When treating patients with diabetes mellitus (DM), the benefits of antiplatelet therapy in preventing cardiovascular disease must be weighed against an increased risk of bleeding. Recent trials have sought to determine both the optimal anti-platelet regimen for patients with DM, and who specifically requires medication among the DM population. This paper will review recent trials and evidence recommending the use of antiplatelet therapy in the prevention of cardiovascular disease in patients with diabetes. Seven notable trials assessed the effectiveness of antiplatelet therapy in the DM population. The ASCEND trial concluded 100mg aspirin/day reduced rates of serious vascular events (OR 0.88, p < 0.01) but also increased rates of major bleeding events (OR 1.29, p < 0.01). The DAPT study revealed a longer dual antiplatelet regimen (30months vs. 18months) after coronary stent placement was more effective in reducing rates of stent thrombosis (0.5% vs. 1.1%, p = 0.06) and rates of myocardial infarction (3.5% vs. 4.8%, p = 0.06). DECLARE DIABETES showed that adding cilostazol to dual antiplatelet therapy after a coronary stent procedure reduced rates of in-stent and in-segment late loss and increased rates of revascularization (p < 0.04). In PEGASUS-TIMI, daily ticagrelor demonstrated reduced rates of major adverse cardiovascular and cerebrovascular events (OR 0.84, p < 0.04). The DAVID trial compared daily picotamide with daily aspirin therapy, finding reduced mortality rates in the picotamide group (OR 0.55, p < 0.05). Lastly, ACUITY found bivalirudin monotherapy resulted in lower rates of major bleeding events when compared to a glycoprotein IIb/IIa inhibitor and heparin or bivalirudin combination regimen (p < 0.01). Dual antiplatelet therapy guidelines still typically revolve around aspirin, but an increasing number of studies have demonstrated other drugs that may have a role in preventing atherosclerotic cardiovascular disease while decreasing the risk of major bleeding. Overall, it is wise to weigh the cardiovascular risk of a DM patient before prescribing antiplatelet medication. More research is necessary to determine a universal drug or combination of drugs that is safe and effective for DM patients.

Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited. To investigate the association of daily aspirin therapy with HBV-related HCC risk. In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018. Daily aspirin therapy during the study period. Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event. Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk. Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

A Retrospective Analysis of Esophageal Eosinophilia in Patients with Aspirin-exacerbated Respiratory Disease

Gastrointestinal symptoms are the most common side effect leading to discontinuation of aspirin therapy in patients with aspirin-exacerbated respiratory disease (AERD). Some patients with gastrointestinal symptoms on high-dose aspirin demonstrated biopsy-proven esophageal eosinophilia (EE). In a large cohort of patients with AERD we report on this novel clinical entity. Charts from 387 patients enrolled in the Brigham and Women’s Hospital AERD registry were reviewed for history of biopsy-proven EE. All subjects were diagnosed with AERD by a Partners Healthcare physician. Data was analyzed using student’s t-test and chi-square tests where appropriate. 13 (3.4%) patients had a history of biopsy-proven EE documented in the medical chart. 10 of 13 were desensitized to aspirin with 9 of them first developing EE 3 months to 6 years after aspirin initiation. AERD subjects with EE demonstrated greater rates of gastric irritation at follow-up visits (p<0.001) and of aspirin discontinuation due to gastric irritation (p=0.013, Pearson’s Chi-Squared test) than the non-EE group. Those with EE reported a faster rate of nasal polyp regrowth compared to the non-EE group (4.75±3.35 versus 14.9±20.8 months, p<.0001). Our study is the first to explore the relationship between aspirin therapy in AERD and the development of EE. We observed that EE develops in subjects with AERD both before and after initiation of daily aspirin therapy with more cases reported after starting aspirin. We found that the presence of EE is associated with faster regrowth of nasal polyps suggesting more severe sino-nasal mucosal pathology in this population.

Identification of aspirin resistance using a PDW-miR92a-score: Validation in an intermittent claudication cohort

ObjectiveAspirin is a widely used platelet inhibitor to prevent thrombotic events. However, in 25% of patients the antiplatelet effect is insufficient. The current study aimed to validate a newly developed PDW-miR92a-score as a biomarker of the individual response to aspirin enabling targeted antithrombotic therapy. MethodsBlood samples were collected from 209 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test, patients were defined as aspirin resistant (n = 92) or responders (n = 117). Using the cut-off values for platelet distribution width (PDW) and plasma levels of microRNA-92a (miR-92a) defined in our pilot study, we investigated the performance of the combined PDW-miR92a-score in the validation study. Furthermore, receiver operating characteristic curve analysis was performed in the validation cohort in order to optimize the cut-off values of the two score parameters. ResultsPDW and miR-92a levels were significantly higher in aspirin resistant compared to responding patients. When using the predefined cut-off values for PDW and miR-92a the combined PDW-miR92a score showed high specificity (93.1%) but poor sensitivity (19.8%) for aspirin resistance. By recalculation using new cut-off values identified in the validation cohort, a score with a specificity of 75% and a sensitivity of 54.9% was obtained. ConclusionBoth PDW and plasma levels of miR-92a were confirmed to be significantly higher in aspirin resistant compared to responding patients in our validation cohort. We were, however, unable to confirm the high sensitivity of the combined PDW-miR92a-score previously published by our group in a pilot study.

Effect of Aspirin on Disability-free Survival in the Healthy Elderly

BackgroundInformation on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.MethodsFrom 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage.ResultsA total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001).ConclusionsAspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

Long-term Clinical Outcomes of Aspirin Desensitization With Continuous Daily Aspirin Therapy in Aspirin-exacerbated Respiratory Disease.

Background Aspirin-exacerbated respiratory disease (AERD), also known as Samter's triad or aspirin (ASA)-intolerant asthma, affects 7% of asthmatics and has a higher prevalence in those with chronic rhinosinusitis and concomitant nasal polyposis. ASA desensitization with daily ASA therapy is a uniquely beneficial treatment for this disease entity and has been shown to have a significant impact on symptom scores, polyp disease, and need for systemic corticosteroids. However, no long-term studies have demonstrated whether or not ASA therapy remains safe and beneficial for these patients beyond 5-10 years. Objective This study was designed to determine the clinical course of AERD patients desensitized between 1995 and 2010. Methods A 20-question survey was distributed to patients who successfully completed ASA desensitization between January 1995 and April 2010. The questions were designed to assess ASA safety and longitudinal effects of ASA therapy in AERD. Results Of the 285 patients contacted, 92 (32%) completed the questionnaire. Average length of follow-up was 15 years. Of survey responders, 35 patients had discontinued ASA therapy. Although adverse reactions occurred, many also discontinued due to lack of efficacy or need for surgery. For those remaining on ASA (62%), significant improvement in sense of smell, asthma, sinus, and allergic rhinitis scores were noted ( P ≤ .001). The majority of ASA patients (68%) had a positive response to treatment and did not require further sinus surgery. However, ASA therapy did not delay the time to next sinus/polyp surgery ( P = .27) or reduce total number of sinus surgeries ( P = .56) compared to those who stopped treatment. Nearly 85% of AERD patients on ASA therapy found it to be helpful in improving airway disease and quality of life. Conclusion Aspirin desensitization followed by daily maintenance ASA therapy appears to be safe and effective even after 10+ years of continuous use.

Contemporary management of chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease: an evidence-based review with recommendations.

Chronic rhinosinusitis (CRS) in aspirin-exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD. A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population >18 years old; CRS based on published diagnostic criteria, and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology (AAO) guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment. This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification, and desensitization with daily aspirin therapy. Based on the available evidence, dietary salicylate avoidance and leukotriene-modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision endoscopic sinus surgery (ESS).

Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width

ObjectiveAspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events. This study aimed to investigate the value of circulating miR-92a and platelet size as biomarkers of the individual response to aspirin therapy. MethodsBlood samples were collected from 50 healthy blood donors without antithrombotic medication and 50 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test on Multiplate®analyzer (ASPItest), patients were defined as aspirin resistant (n=10) or aspirin responders (n=40). Plasma levels of miR-92a were evaluated by RT-qPCR analysis and platelet distribution width (PDW) was used to assess platelet size variability. Receiver operating characteristic curves for miR-92a levels and PDW were used to set cut-off values for discrimination between aspirin responding and aspirin resistant patients. ResultsWhen defining aspirin resistance as an ASPItest ≥30U, the optimal cut-off values for discrimination of aspirin responders and aspirin resistant patients were found to be PDW>11.8fL and a relative expression level of miR-92a>4.5. Using these cut-off values we could define a PDW/miR-92a-score with a specificity of 97.5% and a sensitivity of 80.0% in relation to detect aspirin resistance. The corresponding positive and negative predictive values were found to be 88.9% and 95.1%, respectively. ConclusionAspirin resistance can potentially be identified by miR-92a levels in plasma combined with PDW.