AUTHOR=Sciacqua Angela , Andreozzi Francesco , Succurro Elena , Pastori Daniele , Cammisotto Vittoria , Armentaro Giuseppe , Mannino Gaia C. , Fiorentino Teresa Vanessa , Pignatelli Pasquale , Angiolillo Dominick J. , Sesti Giorgio , Violi Francesco 

TITLE=Impaired Clinical Efficacy of Aspirin in Hypoalbuminemic Patients With Diabetes Mellitus

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.695961

DOI=10.3389/fphar.2021.695961

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To investigate the impact of albumin levels on the aspirin efficacy, since aspirin inhibits platelet aggregation (PA) by cyclooxygenase one irreversible acetylation that is less effective in patients with type 2 diabetes mellitus (T2DM).</p><p><bold>Patients and Methods:</bold> A total of 612 aspirin (100 mg/day)-treated T2DM patients were followed-up for 54.4 ± 7.3 months. The primary endpoint, a composite of cardiovascular events (CVEs) including CV death, myocardial infarction, ischemic stroke and coronary revascularization, was analysed according to baseline values of serum albumin (≥ or &lt; 3.5 g/dL). Serum thromboxane (Tx)B<sub>2</sub> was also measured.</p><p><bold>Results:</bold> 250 (40.8%) patients had serum albumin &lt; 3.5 g/dL; these patients were overweight and had higher values of fibrinogen (<italic>p</italic> = 0.009), high sensitivity C-reactive protein (<italic>p</italic> = 0.001) and fasting plasma glucose (<italic>p</italic> &lt; 0.0001) compared to those with albumin ≥ 3.5 g/dL. During follow-up, 86 CVEs were recorded, 49 and 37 in patients with serum albumin &lt; or ≥3.5 g/dL, respectively (<italic>p</italic> = 0.001). At multivariable Cox regression analysis, serum albumin &lt; 3.5 g/dL (hazard ratio [HR] 1.887, 95% confidence interval [CI] 1.136–3.135, <italic>p</italic> = 0.014), age (HR 1.552 for every 10 years, 95%CI 1.157–2.081, <italic>p</italic> = 0.003), fasting plasma glucose (HR 1.063, 95%CI 1.022–1.105, <italic>p</italic> = 0.002) and beta-blocker use (HR 0.440, 95%CI 0.270–0.717, <italic>p</italic> = 0.001) were associated to CVEs. Serum TxB<sub>2</sub> levels (<italic>n</italic> = 377) were 0.32 ± 0.12 and 0.24 ± 0.12 ng/ml in patients with albumin &lt; or ≥ 3.5 g/dL, respectively (<italic>p</italic> &lt; 0.001).</p><p><bold>Conclusion:</bold> In T2DM patients, the efficacy of aspirin varies according to albumin levels. Hypoalbuminemia associated with impaired TxB<sub>2</sub> inhibition and an increased risk of long-term CVEs.</p>