Utility of VerifyNow to assess the immediate pharmacodynamic response of chewed and swallowed aspirin: comparison with aggregometry.

VerifyNow (VN) test is a less laborious method to assess pharmacodynamics (PD) compared to light transmittance aggregometry (LTA). VN assay has not been used to study the immediate PD effects of acetylsalicylic acid (ASA). Ten healthy volunteers were randomly assigned to a single 162 or 650 mg dose of chewed and swallowed ASA. Pharmacodynamic and pharmacokinetic measurements were performed at baseline and serially up to 60 min after ASA administration. Onset by VN was 20 ± 7 min with 162 mg and 13 ± 7 min with 650 mg ASA (p = .07). Onset by 1 mM AA-induced PA was 13 ± 12 min with 162 mg and 7 ± 3 min with 650 mg ASA (p=NS). VN correlated with AA-induced PA (r = 0.80, p < .001) and serum TxB2 levels (r = 0.76, p < .001). 95% inhibition of serum TxB2 was achieved at 38 ± 22 min and 22 ± 8 min with the 162 and 650 mg ASA, respectively (p = .08). The onset and extent of the antiplatelet effect of 650 mg ASA is numerically faster and greater than the 162 mg dose. VN identifies the onset, extent, and dose response to ASA therapy. The ease of using VN should facilitate multicenter PD investigations of ASA.

Aspirin (acetylsalicylic acid) is an important drug widely used to prevent adverse ischemic events in patients with cardiovascular disease. Platelet aggregation and thromboxane B₂ levels in blood samples by complex laboratory methods are used to assess platelet response to aspirin. VerifyNow assay is a simple laboratory test that has not been used to assess the immediate effect of aspirin. In this study, conducted in 10 healthy volunteers, we compared the immediate platelet response to aspirin by serially assessing platelet aggregation by aggregometry and VerifyNow assay, and thromboxane B₂ levels. We also measured plasma levels of acetylsalicylic acid and salicylic acid. Our study demonstrated that the VerifyNow Aspirin test identifies the onset, extent, and dose-response to aspirin therapy. The ease of using the VerifyNow test should facilitate multicenter pharmacodynamic investigations of aspirin.

Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.

Effect of COVID-19 Pandemic on PCI Outcomes: A Single-center Retrospective Race and Gender-based Study.

African Americans (AAs) have a higher risk for postpercutaneous coronary intervention (PCI) ischemic events and worse Coronavirus Disease 2019 (COVID-19)-related events than non-AAs. Race and gender-related post-PCI events before and during the COVID-19 pandemic in a community hospital setup are unknown. Demographics and one-year adverse events in patients undergoing PCI immediately before (2018-2020) and during (2020-2021) pandemic were compared. About 291 and 292 non-AAs and 220 and 219 AAs who underwent PCI before and during the pandemic, respectively, were included. AAs were younger than non-AAs and had a higher prevalence of diabetes and acute coronary syndrome during the pandemic (P < 0.01 for all). Although total ischemic events were the same, cardiovascular death and myocardial infarction were higher during COVID-19 (P < 0.05) and were more prevalent among AAs. The highest ischemic events were observed in AA women during the pandemic compared to other gender and races. These data highlight the high intrinsic thrombogenicity phenotype in AA women.

An update on novel therapies for treating patients with arterial thrombosis.

INTRODUCTION: Antithrombotic therapy field is undergoing rapid and significant changes during the past decade. In addition to new therapeutic strategies with existing targets, investigators are exploring the potential use of new targets to address unmet needs to treat patients with arterial diseases. AREAS COVERED: We aim to provide an update on and a comprehensive review of the antithrombic agents that are being explored in patients with arterial diseases. We discuss latest developments with respect to upstream antiplatelet agents, and collagen and thrombin pathway inhibitors. We searched PubMed databases for English language articles using keywords: antiplatelet agents, thrombin pathway inhibitors, collagen receptors, arterial disease. EXPERT OPINION: Despite implementation of potent P2Y12 inhibitors, there are numerous unmet needs in the treatment of arterial diseases including ceiling effect of currently available antiplatelet agents along with and an elevated risk of bleeding. The latter observations encouraged investigators to explore new targets that can attenuate the generation of platelet-fibrin clot formation and subsequent ischemic event occurrences with minimal effect on bleeding. These targets include collagen receptors on platelets and thrombin generation including FXa, FXIa, and FXIIa. In addition, investigators are studying novel antiplatelet agents/strategies to facilitate upstream therapy in high-risk patients.

An evaluation of the AggreGuide A-100 ADP Assay for measuring the effect of antiplatelet agents targeting the P2Y12 receptor.

INTRODUCTION: Currently available platelet function assays largely ignore the important characteristics of in vivo thrombus generation, such as flow conditions and shear. The AggreGuide A-100 ADP Assay detects platelet aggregation in whole blood using light scattering under flow conditions. AREAS COVERED: In this review article, we discuss the limitations of currently available platelet function assays and the technology underlying the AggreGuide A-100 ADP assay. We also discuss the results of the validation assay study. EXPERT OPINION: By incorporating arterial flow conditions and shear, the AggreGuide assay may be more indicative of in vivo thrombus generation as compared to currently available platelet function assays. As per the United States, Food and Drug administration, the AggreGuide A-100 ADP test has been cleared to assess antiplatelet effects of prasugrel and ticagrelor. The assay results are comparable to widely used VerifyNow PRU assay. The utility of AggreGuide A100-ADP Assay in guiding P2Y12 receptor inhibitor therapy in patients with cardiovascular disease needs to be explored in clinical studies.

Serial assessment of thrombogenicity and hemodynamics in patients with type II diabetes in a clinical research unit: Evidence for circadian variations in clot formation.

BACKGROUND: Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population. METHODS: This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening). RESULTS: R-value measured by TEG was shorter during awakening hours than during the night and day hours (p < 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p < 0.05). CONCLUSION: Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.

Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes.

Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Our aim was to explore the effects of metformin on markers of inflammation, oxidative stress, and hypercoagulability, and on clinical outcomes. Patients with DM on metformin (n = 34) and metformin naïve (n = 41), and patients without DM (n = 73) were enrolled within 48 h of hospital admission for COVID-19. Patients on metformin compared to naïve patients had a lower white blood cell count (p = 0.02), d-dimer (p = 0.04), urinary 11-dehydro thromboxane B2 (p = 0.01) and urinary liver-type fatty acid binding protein (p = 0.03) levels and had lower sequential organ failure assessment score (p = 0.002), and intubation rate (p = 0.03), fewer hospitalized days (p = 0.13), lower in-hospital mortality (p = 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p = 0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate. In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.