Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective, randomized, crossover study

Abstract

Low dose enteric-coated aspirin (EC-ASA) is routinely used for secondary cardiovascular event prevention. However, absorption of EC tablets is poor, which can result in subtherapeutic antiplatelet effects. Phospholipid-aspirin liquid filled capsules (PL-ASA) are a novel FDA-approved immediate-release formulation designed to reduce gastrointestinal (GI) injury by limiting direct contact with the stomach lining. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of PL-ASA versus EC-ASA at a low dose. This randomized, open-label, crossover study assessed PK and PD following a single 81-mg dose of PL-ASA versus EC-ASA under fasting conditions in 36 volunteers without cardiovascular disease between 18 and 75 years of age. Volunteers were randomly assigned 1:1 to either PL-ASA then EC-ASA or vice versa with a minimum 14-day washout. Assessments included PK parameters for acetylsalicylic acid and salicylic acid, platelet aggregation in response to arachidonic acid (AA), and serum thromboxane B2 (TxB2) assessments over 24 h. PL-ASA was rapidly absorbed. PL-ASA reached Tmax 3 h earlier (1.01 vs. 4.00 h, p < 0.0001), with almost double the Cmax (720 vs. 368 ng/mL, p < 0.0001) and overall 44% higher exposure of acetylsalicylic acid (AUC0-t: 601 vs. 416 h*ng/mL, p = 0.0013) compared with EC-ASA. Within 1 h of dosing, PL-ASA achieved significantly lower residual platelet aggregation, which persisted for the full 24 h (median AA-LTA was 47% with PL-ASA vs. 80.5% with EC-ASA; p = 0.0022 at hour-24). Treatment with PL-ASA also resulted in significantly lower serum TxB2 concentrations at each time point compared with EC-ASA (all p-values < 0.05). PL-ASA resulted in faster and more complete aspirin absorption paralleled by more prompt and potent platelet inhibition compared with EC-ASA after a single 81 mg dose. PL-ASA represents an attractive novel aspirin formulation for the secondary prevention of cardiovascular events.Clinical Trial Registration ClinicalTrials.gov identifier: NCT04811625.

Indobufen or Aspirin on Top of Clopidogrel After Coronary Drug-Eluting Stent Implantation (OPTION): A Randomized, Open-Label, End Point–Blinded, Noninferiority Trial

“…35 A lipid-based formulation of aspirin has been shown to reduce gastrointestinal injury and to be associated with better and faster absorption than enteric‑coated aspirin. 6,36,37 Such a novel formulation of aspirin might be an attractive treatment option in the future and warrants further investigation in clinical trials.…”

“…35 A lipid-based formulation of aspirin has been shown to reduce gastrointestinal injury and to be associated with better and faster absorption than enteric-coated aspirin. 6,36,37 Such a novel formulation of aspirin might be an attractive treatment option in the future and warrants further investigation in clinical trials. Of note, our study population represents a low-risk population with chronic coronary syndromes (CCSs), although more than half of the patients were classi-fied as having unstable angina.…”

Aspirin for the Primary Prevention of Vascular Ischemic Events: An Updated Systematic Review and Meta-analysis to Support Shared Decision-Making

“… ‡ The ISTH criteria are defined as follows: (i) fatal bleeding; (ii) bleeding in a critical site or area (retroperitoneal, cardiac tamponade, hemoptysis, intraocular, intracranial, definite hemorrhagic stroke or subarachnoid hemorrhage); or (iii) bleeding causing a fall in hemoglobin level of 20 g/L or more or leading to transfusion of 2 or more units of blood. 34 …”

“… 32 Another formulation, phospholipid-aspirin complex, is associated with reduced gastrointestinal injury and predictable absorption that may mitigate the GIB risk. 33 , 34 Whether this formulation provides a more favourable safety profile in a primary prevention population remains to be demonstrated. Also unclear is whether coadministration of ASA and a gastroprotective agent, such as a proton pump inhibitor, sufficiently mitigates the GIB risk, 35 such that ASA would be more broadly acceptable in a primary prevention context, particularly given the uncertainty regarding the cost-effectiveness of this approach.…”

Long-Term P2Y 12 Inhibitor or Aspirin as Single Antiplatelet Therapy in Patients With Previous Percutaneous Coronary Intervention

“…Remaining questions include the comparative lifetime effectiveness, safety, and cost-effectiveness of P2Y 12 inhibitors and aspirin; the role of ticagrelor and prasugrel as single antiplatelet agents versus aspirin after PCI; and the merits of P2Y 12 inhibitor monotherapy versus novel aspirin formulations characterized by ameliorated absorption and gastrointestinal safety. 13 A large-scale definitive trial comparing different monotherapies after guideline-directed dual antiplatelet therapy is a much-needed addition to the list of ongoing investigations of antiplatelet strategies for PCI.…”