Aspirin Maintenance Therapy Research Articles

GASTROINTESTINAL SYMPTOMS WITH ASPIRIN-EXACERBATED RESPIRATORY DISEASE MAY INCREASE RISK FOR FAILURE DURING RAPID ASPIRIN DESENSITIZATION

<h3>Introduction</h3> Aspirin-exacerbated respiratory disease (AERD) is a chronic condition with polyposis, asthma, and sensitivity to nonsteroidal anti-inflammatory drugs. Management of AERD is often through aspirin desensitization, which historically was a two-day or longer process. Few studies have examined specific phenotypes with the safety and efficacy of a one-day oral aspirin desensitization protocol. <h3>Methods</h3> We completed a single-center, retrospective chart review analyzing all patients with AERD who underwent a rapid, one-day aspirin desensitization from October 2018-April 2022. Descriptive statistics were used to analyze the data. <h3>Results</h3> Thirty-two of 36 (89%) subjects underwent successful aspirin desensitization. Sixty-six percent (21/32) of successful desensitization were completed in a single day (6.4 hours) and 34% (11/32) in two days (9.4 hours). The most common dose to illicit symptoms was 81 mg in the one-day group and 120 mg in the two-day group. Sinonasal symptoms during the reaction were the most common in both groups. Thirty-eight percent (8/21) of the one-day subjects discontinued aspirin maintenance therapy with 50% (4/8) initiating dupilumab. Similarly, 27% (3/11) of the two-day group discontinued aspirin with 33% (1/3) initiating dupilumab. Of the 4 subjects who failed desensitization, 3 had severe gastrointestinal symptoms with 1 requiring epinephrine at the clinic. <h3>Conclusion</h3> A single-day oral aspirin desensitization procedure appears safe and effective for AERD. Patients who failed desensitization more likely had gastrointestinal reactions to aspirin. Further research is necessary to explore the role of gastrointestinal reactions in AERD and the likelihood of failing aspirin desensitization.

Hypereosinophilia following aspirin desensitization for aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is an inflammatory syndrome characterized by the triad of asthma, chronic rhinosinusitis with nasal polyposis, and sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).1 Its pathogenesis is related to deranged arachidonic acid metabolism leading to elevated levels of cysteinyl leukotrienes (CysLTs) and prostaglandin D2, both of which contribute to eosinophilia found in AERD.1,2 Aspirin desensitization followed by maintenance aspirin therapy has been shown to be beneficial at reducing symptoms in patients with AERD, although its mechanism for doing so remains unproven.

Aspirin Actions in Treatment of NSAID-Exacerbated Respiratory Disease.

Non-steroidal Anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyposis, chronic rhinosinusitis, adult-onset asthma and hypersensitive reactions to cyclooxygenase-1 (COX-1) inhibitors. Among the available treatments for this disease, a combination of endoscopic sinus surgery followed by aspirin desensitization and aspirin maintenance therapy has been an effective approach. Studies have shown that long-term aspirin maintenance therapy can reduce the rate of nasal polyp recurrence in patients with N-ERD. However, the exact mechanism by which aspirin can both trigger and suppress airway disease in N-ERD remains poorly understood. In this review, we summarize current knowledge of aspirin effects in N-ERD, cardiovascular disease, and cancer, and consider potential mechanistic pathways accounting for the effects of aspirin in N-ERD.

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.

Systematic review of outcomes for endoscopic sinus surgery and subsequent aspirin desensitization in aspirin-exacerbated respiratory disease.

ObjectiveTo review and evaluate outcomes of patients with aspirin-exacerbated respiratory disease (AERD) following endoscopic sinus surgery and subsequent aspirin desensitization.MethodsElectronic searches of OVID MEDLINE (1948 to September 10, 2019), EMBASE (1980 to September 10, 2019), and PubMed were performed on September 10, 2019. A systematic review of the literature was performed using the 2009 PRISMA guidelines. Studies with both preoperative and postoperative data for patients with AERD who underwent sinus surgery and aspirin desensitization were considered appropriate for inclusion. Publications were written in English and included patients aged 18 years or older.ResultsSix studies met inclusion criteria for this systematic review. The primary outcome measure was change in symptom profile measured by patient-reported quality of life scores. The results demonstrate statistically significant improvement in symptoms following endoscopic sinus surgery, with sustained improvement following aspirin desensitization. Revision surgery rates were significantly lower in patients maintained on aspirin therapy.ConclusionThis review suggests that surgery followed by aspirin desensitization results in improvement in both subjective and objective outcome measures. The adjunctive use of aspirin desensitization allows for long-term stability in symptom scores. Recurrence of polyps and worsening symptoms requiring revision surgery occurs when aspirin maintenance therapy is interrupted.

Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease.

In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin-exacerbated respiratory disease (AERD). A retrospective chart review was conducted for patients with aspirin challenge-proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality-of-life measures using the 22-item Sino-Nasal Outcomes Test (SNOT-22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post-desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed-effects model was used for data analysis. Thirty-four patients met the inclusion criteria for this study. Thirty-two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow-up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT-22 scores. Our results demonstrate that total SNOT-22 scores remained statistically unchanged from immediate post-desensitization throughout the 30-month follow-up period. Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long-term management of sinus disease in patients with AERD.

Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI

Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN > 242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r = 0.69) and LTA vs. MEA (r = 0.56), with moderate agreement (κ = 0.46 and κ = 0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r = 0.42) and agreement (κ = 0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.

Impact of renal function on clopidogrel-induced antiplatelet effects in coronary artery disease patients without diabetes mellitus

Diabetes mellitus (DM) is the most important predictor of chronic kidney disease (CKD), and pharmacodynamic (PD) studies have shown that DM patients with impaired renal function are characterized by reduced clopidogrel response. However, post-hoc PD studies conducted in unselected cohorts, composed of both DM and non-DM patients, have reached controversial findings on the effects of CKD on clopidogrel response, likely attributed to patient heterogeneity. The impact of renal function on clopidogrel response in non-DM patients remains unexplored and represented the aim of this prospective investigation. We conducted a prospective PD investigation in non-DM patients with and without CKD defined as an estimated glomerular filtration rate (eGFR) below or above 60mL/min, respectively. All patients had known coronary artery disease and were on maintenance aspirin therapy. PD assessments were assessed at baseline and 2 and 24h after a 600mg loading dose of clopidogrel. PD assays included light transmission aggregometry (LTA) using 5 and 20μmol ADP with and without PGE1 and flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) to determine the platelet reactivity index. A total of 60 patients were studied (n=30 eGFR ≥60mL/min; n=30 eGFR <60mL/min). At baseline there were no differences between groups. Following clopidogrel loading dose administration, levels of on-treatment platelet reactivity were similar between groups at 2 and 24h as measured with LTA and VASP. Accordingly, there were no differences in rates of high on-treatment platelet reactivity between groups. In non-DM patients with CAD, the presence of impaired renal function is not associated with differences in clopidogrel-induced antiplatelet effects compared with patients with preserved renal function.

Therapeutic Management of Recurrent Peptic Ulcer Disease

The epidemiology of peptic ulcer disease (PUD) has undergone significant changes since the discovery of Helicobacter pylori. Various aetiologies contribute to recurrent PUD. Ulcers related to untreated H. pylori infection tend to recur. Use of NSAIDs, low-dose aspirin and dual anti-platelet therapy have become important risk factors for recurrent ulcers and their complications as the proportion of H. pylori-related ulcers declines. Recent data have shown that H. pylori-negative, NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk of recurrent ulcer bleeding and mortality. Effective management of recurrent PUD relies on identification and modification of treatable risk factors. Persistent H. pylori infection should be carefully ruled out. Choice of an effective H. pylori eradication regimen should be based on local antibacterial resistance patterns. For patients who need long-term NSAID therapy, the initial choice of an NSAID relates to a patient's cardiovascular risk, and the need for therapy to decrease gastrointestinal (GI) complications is determined by the severity and number of GI risk factors. For patients on dual anti-platelet therapy, strategies to prevent recurrent ulcer disease and its complications centre on balancing the bleeding and thrombotic risks of individual patients. Long-term proton pump inhibitor maintenance therapy may be necessary to prevent recurrent ulcer bleeding for patients with ulcer bleeding from H. pylori-negative, NSAID-negative ulcers, and for patients who require NSAID or aspirin maintenance therapy.

Abstracts From the Emerging Science Series, June 27, 2011

1 First Human Use of an Allogeneic Tissue Engineered Vascular Graft Todd N. McAllister, Cytograft/St. Joseph's Translational Res Inst, Novato, CA; Wojciech Wystrychowski, Medical UNiversity of Silesia, Katowice, Poland; Lech Cierpka, Krzysztof Zagalski, Medical Univ of Silesia, Katowice, Poland; Sergio A. Garrido, Fleni Hosp, Buenos Aires, Argentina; Samuel Radochonski, Nathalie Dusserre, Cytograft, Novato, CA; Nicolas L'Heureux, Cytograft/St. Joseph's Translational Res Inst, Novato, CA Introduction: End Stage Renal Disease (ESRD) is one of the most costly chronic diseases in the industrialized world. In the U.S., more than $27 billion is expended annually for the care of 400,000 dialysis patients. Creation and maintenance of access shunts is one of the principal challenges associated with dialysis, and accounts for 15% of all ESRD-related expenses. A more effective solution to hemodialysis access remains one of the key objectives in vascular surgery today. Previously we reported promising results with the first human patients to receive a completely autologous tissue engineered vascular graft (TEVG) for hemodialysis access. With time points out to 3 years, we observed a 2.4-fold reduction in events relative to the pre-enrollment rates with the standard of care. The complexities of the autologous model, however, make it difficult to translate to widespread clinical use. We hypothesized that an allogeneic TEVG, available ‘off-the-shelf,’ would have similar benefits and may demonstrate improved efficacy and cost-effectiveness relative to synthetic grafts. Here we report the first human …

Ticagrelor Compared With Clopidogrel by Geographic Region in the Platelet Inhibition and Patient Outcomes (PLATO) Trial

In the Platelet Inhibition and Patient Outcomes (PLATO) trial, a prespecified subgroup analysis showed a significant interaction between treatment and region (P=0.045), with less effect of ticagrelor in North America than in the rest of the world. Reasons for the interaction were explored independently by 2 statistical groups. Systematic errors in trial conduct were investigated. Statistical approaches evaluated the likelihood of play of chance. Cox regression analyses were performed to quantify how much of the regional interaction could be explained by patient characteristics and concomitant treatments, including aspirin maintenance therapy. Landmark Cox regressions at 8 time points evaluated the association of selected factors, including aspirin dose, with outcomes by treatment. Systematic errors in trial conduct were ruled out. Given the large number of subgroup analyses performed and that a result numerically favoring clopidogrel in at least 1 of the 4 prespecified regions could occur with 32% probability, chance alone cannot be ruled out. More patients in the United States (53.6%) than in the rest of the world (1.7%) took a median aspirin dose ≥300 mg/d. Of 37 baseline and postrandomization factors explored, only aspirin dose explained a substantial fraction of the regional interaction. In adjusted analyses, both Cox regression with median maintenance dose and landmark techniques showed that, in patients taking low-dose maintenance aspirin, ticagrelor was associated with better outcomes compared with clopidogrel, with statistical superiority in the rest of the world and similar outcomes in the US cohort. The regional interaction could arise from chance alone. Results of 2 independently performed analyses identified an underlying statistical interaction with aspirin maintenance dose as a possible explanation for the regional difference. The lowest risk of cardiovascular death, myocardial infarction, or stroke with ticagrelor compared with clopidogrel is associated with a low maintenance dose of concomitant aspirin. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Cardiovascular Safety of Celecoxib on Top of Dual Antiplatelet Therapy

Cardiovascular Safety of Celecoxib on Top of Dual Antiplatelet Therapy

Antiplatelet Therapy in Early Management of Non-ST-segment Elevation Acute Coronary Syndrome: The 2002 and 2007 Guidelines From North America and Europe

The American College of Cardiology, American Heart Association, and the European Society of Cardiology published updated guidelines in 2007 for patients with non-ST elevation acute coronary syndrome. In this article, we review the recommendations for antiplatelet therapy and supporting data, highlight new changes, and describe differences between the European and North American guidelines. The new guidelines provide more details regarding the selection of an early conservative versus an early invasive approach based on the patient's profile and balance between ischemic and bleeding risks. Important new recommendations include wider endorsement for low-dose aspirin maintenance therapy, longer duration of clopidogrel following percutaneous coronary intervention, additional guidance regarding surgery in selected patients on clopidogrel, identification of patients most likely to benefit from glycoprotein IIb/IIIa inhibitors (with appropriate dose modification in patients with renal failure), and the option to use early clopidogrel with bivalirudin in patients managed invasively who are at increased risk of bleeding. The new guidelines also discourage the concomitant use of nonsteroidal anti-inflammatory drugs and delineate indications for adding warfarin to antiplatelet therapy. Because antiplatelet therapy is the cornerstone of management of patients with non-ST elevation acute coronary syndrome, health care providers should make themselves familiar with the new data and latest guideline recommendations.

Hydrocortisone sodium succinate does not cross-react with aspirin in aspirin-sensitive patients with asthma

Background: Bronchospasm after intravenous hydrocortisone treatment has been reported in some patients with aspirin-sensitive respiratory disease. Objective: This study was designed to determine the prevalence of sensitivity to hydrocortisone among patients with aspirin-sensitive respiratory disease. Methods: We performed double-blind, placebo-controlled challenges with aspirin and 100 mg of hydrocortisone sodium succinate administered intravenously in 53 subjects. Results: Forty-five of the 53 subjects (85%) undergoing oral aspirin challenge experienced respiratory reactions to aspirin. Forty-four of these 45 patients had neither naso-ocular, cutaneous, nor respiratory reactions to hydrocortisone sodium succinate. One aspirin-sensitive subject had bronchospasm and a naso-ocular reaction to hydrocortisone sodium succinate and a naso-ocular reaction with minimal bronchospasm to methylprednisolone sodium succinate. After desensitization to aspirin, and while receiving maintenance aspirin therapy, this subject again reacted to hydrocortisone sodium succinate with bronchospasm and naso-ocular reaction. Conclusion: We conclude that aspirin-sensitive patients with asthma are not preferentially sensitive to hydrocortisone and that hydrocortisone sodium succinate does not cross-react or cross-desensitize with aspirin. ( J Allergy Clin Immunol 1995;96:545-8.)