Patients with Essential Thrombocythemia may be Poor Responders to Enteric-Coated Aspirin, but not to Plain Aspirin

Essential thrombocythemia (ET) patients are treated with aspirin (acetylsalicylic acid [ASA]) to prevent thrombosis. Previous studies showed that serum thromboxane (Tx) B2 was high 24 hours after enteric-coated (EC)-ASA in ET patients, due to increased number of noninhibited reticulated platelets (RPs), consequent to high platelet turnover, and that ASA should be given twice a day to ET patients. We studied ET patients (n = 17) and healthy subjects (n = 10) on 100 mg EC-ASA once daily; experiments were repeated after 14-day treatment with 100 mg plain-ASA once daily. Serum TxB2, plasma ASA, and salicylic acid (SA) were measured before the morning dose and up to 8 hours thereafter. Blood activity of ASA-deacethylating esterases, in vitro inhibition of collagen-induced TxB2 production by ASA (10–1,000 µM), and number of RP were measured. TxB2 inhibition by ASA in vitro and esterases activities were normal in all subjects. EC-ASA elicited highly variable responses; 6 ET patients were poor responders, as their serum TxB2 was high after EC-ASA; their plasma levels of ASA and SA were low/undetectable. In contrast to EC-ASA, plain ASA decreased serum TxB2 and increased plasma ASA and SA in all subjects. Serum TxB2 was high in ET patients at 24 hours and significantly correlated with RP count (but not RP percentage) and platelet count. Plain ASA should be used in ET patients to inhibit platelets efficiently. The identification of ET patients who might benefit from twice a day ASA could simply be based on their platelet count: since their platelet turnover is not increased, ET patients with normalized platelet count should not need twice a day ASA treatment.

Abstract TP432: Bioavailability of Aspirin in Fasted and Fed States of a Novel Formulation of a Pharmaceutical Lipid-Aspirin Complex

Introduction: Lifelong aspirin therapy is recommended after a TIA or stroke, but dyspeptic symptoms frequently lead to non-adherence. Clinicians often recommend that daily doses be taken with food to reduce these side effects. However, food can interfere with absorption, especially with enteric coated aspirin tablets. Hypothesis: We evaluated whether food interferes with bioavailability of a new, pharmaceutical lipid-aspirin complex (PL-ASA) liquid-filled capsule formulation. Methods: This was a randomized, open label, crossover study in 20 healthy volunteers. Participants fasted for ≥10 hours prior to randomization; if assigned to “fasting” they then received the single 650 mg dose of PL-ASA. If they were randomized to “fed”, they first ate a standard high-fat meal and were dosed 30 minutes later. After a washout period of 10 days each participant crossed over to the other arm and was again dosed with a 650 mg dose of PL-ASA. The primary outcome was the comparison of PK parameters of the primary metabolite salicylic acid (SA) between fasting and fed states. Results: Mean age of participants was 36.8 years and 55% were male. The primary SA PK parameters of AUC 0-t and AUC 0- infinity in the fed state were within 88.7% and 88.8% of concentrations in the fasting state consistent with bio-equivalence (FDA guidance >80%). Mean peak SA concentration was about 25% lower and occurred about 1.5 hours later in the fed state (Figure). Conclusions: Food had a modest effect on the time required to reach peak SA concentration and on the actual peak SA levels after PL-ASA administration, but did not impact the extent of exposure (area under the curve) compared with intake in a fasting state. These data demonstrate that PL-ASA may be co-administered with food without significant variability in absorption, a recognized limitation of coated aspirin formulations.

Prevalence of Gastric and Small-Intestinal Mucosal Injury in Elderly Patients Taking Enteric-Coated Aspirin by Magnetically Controlled Capsule Endoscopy

Objective. To investigate aspirin-related gastric and small-intestinal mucosal injury in elderly patients by magnetically controlled capsule endoscopy (MCCE). Methods. Patients taking enteric-coated aspirin attending the outpatient department of Beijing Anzhen Hospital, Capital Medical University, from September 2017 to July 2019 underwent MCCE to assess injury to the gastric and small-intestinal mucosa. The patients were divided into the elderly group (age≥60 years) and middle-aged group (45 years≤age<60 years), and their clinical data were evaluated. Results. Sixty-eight patients (34 per group) taking enteric-coated aspirin were recruited, and the elderly and middle-aged groups did not differ significantly in sex, history of smoking, history of alcohol consumption, body mass index, or accompanying diseases. In the elderly and middle-aged groups, the gastric Lanza scores were 2.0 (2.0, 3.0) and 2.0 (1.0, 3.0; P=0.192), the numbers of patients with small-intestinal mucosal injuries (at least one erosion and/or ulcer) were 30 (88.2%) and 15 (44.1%; P<0.001), the numbers of patients with more severe small-intestinal mucosal injuries (larger erosion and/or ulcer) were 11 (32.4%) and 3 (8.8%; P=0.033), the numbers of patients with ileal erosion were 22 (64.7%) and 8 (23.5%; P=0.001), and the durations of aspirin use were 30.0 (12.0, 120.0) and 10.5 (2.0–48.0) months (P=0.007), respectively. Conclusions. The rate of small-intestinal mucosal injury was significantly higher in elderly than in middle-aged patients taking enteric-coated aspirin, especially the rate of ileal erosion. MCCE enables the monitoring of aspirin-related gastric and small-intestinal mucosal injury in elderly patients, which can guide treatment decision making.

Yosprala: Coordinated Delivery of a Proton Pump Inhibitor and Aspirin

Objective: Review the pharmacology, pharmacokinetics, efficacy, and safety of Yosprala (aspirin and omeprazole). Data Sources: A literature search was conducted using PubMed with the terms “Yosprala,” “PA8140,” and “PA32540” from the initial year through May, 2019. Additional sources were gathered through bibliographies. Aralez Pharmaceuticals Inc was contacted for manufacturer information. Study Selection and Data Extraction: The sources were narrowed to studies done in English language between 1990 and 2019. All viable clinical trials for the use of Yosprala in the secondary prevention of cardiovascular events were included. Data Synthesis: Yosprala is a coordinated delivery system of immediate-release omeprazole 40 mg and enteric-coated aspirin (325 mg or 81 mg). In 2016, the Food and Drug Administration approved Yosprala for the secondary prevention of cardiovascular or cerebrovascular events (ie, stroke or myocardial infarction). While it is recommended that patients take low-dose aspirin for secondary prevention of these events, many patients cannot tolerate the gastrointestinal (GI) adverse effect profile of the drug. Phase 3 clinical trials have proven that Yosprala significantly lowers the occurrence of GI bleeds and ulcers versus aspirin alone (3.2% and 8.6%, respectively; P ≤ .001). The most common adverse effects include infection, diarrhea, and dyspepsia. Conclusion: Yosprala significantly reduces the occurrence of GI ulcers and seems to be a safe and effective option for the secondary prevention of cardiovascular events.