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Poststenting ischemic events occur despite dual-antiplatelet therapy, suggesting that a “one size fits all” antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy. We investigated the prognostic utility of the strength of adenosine diphosphate (ADP)–induced (MA ADP) and thrombin-induced (MA THROMBIN) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTA ADP) in 225 serial patients after elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over 3 years. Overall, 59 (26%) first ischemic events occurred. Patients with ischemic events had higher MA ADP, MA THROMBIN, and LTA ADP ( P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MA ADP >47 mm had the best predictive value of long-term ischemic events compared with other measurements ( P < .0001), with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate Cox proportional hazards model identified MA ADP >47 mm, MA THROMBIN >69 mm, and LTA ADP >34% as significant independent predictors of first ischemic events at the 3-year time point, with hazard ratios of 10.3 ( P < .0001), 3.8 ( P < .0001), and 4.8 ( P < .0001), respectively. Fifteen bleeding events occurred. Receiver operating characteristic curve and quartile analysis suggests MA ADP ≤31 as a predictive value for bleeding. This study is the first demonstration of the prognostic utility of MA ADP in predicting long-term event occurrence after stenting. The quantitative assessment of ADP-stimulated platelet-fibrin clot strength measured by thrombelastography can serve as a future tool in investigations of personalized antiplatelet treatment designed to reduce ischemic events and bleeding.

Factors associated with platelet reactivity (PR) during ticagrelor maintenance dose (MD) are not well defined. We aimed to examine factors that influence levels of PR during chronic ticagrelor therapy. We performed individual participant data meta-analysis of 445 patients from 8 studies who had PR assessment with the VerifyNow P2Y12 assay (Accumetrics, Inc, San Diego, CA) while on ticagrelor 90 mg twice a day MD for at least 14 days. Distribution of PR during ticagrelor MD was highly skewed toward lower values. No case of high PR (≥230 P2Y12 reaction units [PRU]) was observed. Age and body mass index (BMI) positively affected PR, with every increase in decade and 5 units of BMI resulting in 7.9% and 4.1% increase in PR, respectively. Current smoking status negatively affected PR with 13.7% decrease in PR in current smokers, compared with nonsmokers. Low PR (LPR) was defined as the lowest quartile of PR values (<10 PRU). In multivariate analysis, diabetes mellitus and age >70 years were independently associated with lower probability for LPR with a relative risk (95% CIs) of 0.570 (0.361-0.899) and 0.554 (0.325-0.944), P = .016 and P = .030, respectively. Age, BMI, and current smoking status affect PR during ticagrelor MD. Diabetes mellitus and age >70 years were found to be associated with lower probability for LPR. Further research is required to assess the clinical implications of these findings in ticagrelor-treated patients.

Both high platelet reactivity (HPR) and CYP2C19 genotyping have been proposed to stratify cardiovascular event risk and to personalize maintenance dual antiplatelet therapy (DAPT) in stented patients. However, how well CYP2C19 genotype correlates with HPR in patients on maintenance DAPT is less clear. We determined the association of CYP2C19 loss-of-function (⁎2) and gain-of-function (⁎17) allele status with platelet reactivity in 118 stented patients on DAPT ≥2 weeks and in 143 patients with stable coronary artery disease on aspirin therapy alone. Thirty-three percent and 39% carried at least 1 copy of ⁎2 and ⁎17 alleles, respectively. Neither allele was associated with platelet reactivity in patients on aspirin therapy alone. On DAPT, platelet aggregation was higher in those with ⁎2 allele than noncarriers (P ≤ .01) but did not differ between those with the ⁎17 allele and noncarriers. The prevalence of HPR using the 20 μM adenosine diphosphate–induced aggregation cutpoint was 34% in the total population: 26% in ⁎1/⁎1 homozygotes, 49% in those with the ⁎2 allele, and 20% in those with the ⁎17 allele (P = .006). Determination of diplotype status enhanced identification of HPR. However, platelet function on DAPT is highly variable within diplotype groups. Therefore, CYP2C19 genotype and HPR are imperfect correlates of each other. Because both predict cardiovascular events with similar risk ratios, CYP2C19 genotyping and HPR may provide complementary information to stratify risk and personalized DAPT in stented patients than either alone.

We analyzed the antiplatelet effects of different P2Y12 receptor blockers with VerifyNow P2Y12 assay (VN-P2Y12) and light transmittance aggregometry (LTA). The point-of-care VN-P2Y12 has been used to assess the antiplatelet effects in clopidogrel-treated patients but has not been evaluated in detail in patients treated with ticagrelor. Patients were randomly assigned to either ticagrelor [180 mg loading/90 mg twice daily (n = 37)] or clopidogrel [600 mg loading/75 mg daily (n = 39)] on top of aspirin treatment, and platelet reactivity was measured serially during onset, maintenance, and offset phases. High on-treatment platelet reactivity (HPR) was defined as 5 and 20 μM adenosine diphosphate-induced maximal platelet aggregation ≥46% and ≥59%, respectively, and P2Y12 reaction units ≥235. Platelet function measured by VN-P2Y12 correlated well with LTA (.812 ≤ ρ ≤ .823, P < .001). VN-P2Y12 “BASE” values were consistent during administration of both agents. Calculated and reported percent inhibitions by VN-P2Y12 were similar (difference, −0.6%; 95% agreement limits, −22.9% to 21.6%). Platelet inhibition by VN-P2Y12 during clopidogrel and ticagrelor administrations was comparable to platelet inhibition by LTA. HPR determined by LTA and VN-P2Y12 were well matched, and the risk stratification between the two methods showed strong agreement after both therapies (κ > .7). The VerifyNow P2Y12 assay is effective in assessing the antiplatelet effects and in identifying HPR during clopidogrel or ticagrelor therapy.

High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid–induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

The objective of the study was to determine the prevalence of high on-treatment platelet reactivity (HPR) in coronary artery disease patients enrolled in the ONSET/OFFSET and RESPOND studies. HPR has been linked to the occurrence of adverse events after stenting in patients treated with clopidogrel (C) and aspirin. Prevalence of HPR after treatment with ticagrelor (T), a reversible oral P2Y 12 receptor antagonist developed to overcome the limitations of C, is unknown. Patients were treated with T (n = 106) or C (n = 103) on top of aspirin therapy. HPR was defined by published cutoff points associated with post–percutaneous coronary intervention ischemic risk: >59% 20 μM adenosine diphosphate–induced aggregation (light transmittance aggregometry), >235 P2Y12 reaction unit by VerifyNow P2Y 12 assay (VerifyNow, San Diego, CA), and >50% platelet reactivity index by vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P). Proportion differences for T versus C were analyzed by χ 2 test for each time point. Correlations ( R) were analyzed by the Pearson method. Ticagrelor was associated with a significantly lower prevalence of HPR (0%-8%) compared with C (21%-81%) at 2, 4, 8, and 24 hours and ≥2 weeks postdosing ( P < .0001, for all assays). The R values between light transmittance aggregometry and VerifyNow/VASP-P were all ≥0.43, P < .0001. The above data represent the largest serial pharmacodynamic evaluation of the comparative effects of T versus C. Ticagrelor was rapidly and consistently associated with a very low prevalence of HPR compared with C, as determined by multiple established methods to measure platelet reactivity. These results provide a mechanism for the lower ischemic event rate associated with T therapy reported in the PLATO trial.

Pharmacologic therapy options for COVID-19 should include antiviral, anti-inflammatory, and anticoagulant agents. With the limited effectiveness, currently available virus-directed therapies may have a substantial impact on global health due to continued reports of mutant variants affecting repeated waves of COVID-19 around the world. We searched articles pertaining to aspirin, COVID-19, acute lung injury and pharmacology in PubMed and provide a comprehensive appraisal of potential use of aspirin in the management of patients with COVID-19. The scope of this article is to provide an overview of the rationale and currently available clinical evidence that supports aspirin as an effective therapeutic option in COVID-19. Experimental and clinical evidence are available for the potential use of aspirin in patients with COVID-19. Aspirin targets the intracellular signaling pathway that is essential for viral replication, and resultant inflammatory responses, hypercoagulability, and platelet activation. With these multiple benefits, aspirin can be a credible adjunctive therapeutic option for the treatment of COVID-19. In addition, inhaled formulation with its rapid effects may enhance direct delivery to the lung, which is the key organ damaged in COVID-19 during the critical initial course of the disease, whereas the 150-325 mg/day can be used for long-term treatment to prevent thrombotic event occurrences. Being economical and widely available, aspirin can be exploited globally, particularly in underserved communities and remote areas of the world to combat the ongoing COVID-19 pandemic.

Studies have linked on-treatment platelet reactivity (PR) to adverse clinical outcomes. Because new P2Y12 inhibitors (prasugrel and ticagrelor) have been predominantly tested against clopidogrel, data on pharmacodynamic comparisons between these 2 drugs are scarce. We compared ticagrelor with prasugrel in a network meta-analysis. PubMed, Cochrane, and EMBASE were searched for studies assessing PR in patients with coronary artery disease treated with ticagrelor or prasugrel. All studies using prasugrel and/or ticagrelor providing platelet function measurement data using VerifyNow P2Y12 reaction units (PRUs), platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein phosphorylation, or maximal platelet aggregation (MPA) by light transmission aggregometry were considered eligible. Mixed treatment comparison models directly compared ticagrelor and prasugrel and indirectly compared them using clopidogrel as a comparator with data presented as mean difference (95% confidence interval). Data were extracted from 29 studies, including 5,395 patients. Compared with clopidogrel 75 mg, both prasugrel 10 mg and ticagrelor 90 mg twice daily were associated with lower PRU (mean difference −117 [−134.1, −100.5] and −159.7 [−182.6, −136.6], respectively), a lower PRI (−24.2 [−28.2, −20.3] and −33.6 [−39.9, −27.6], respectively), and lower MPA (−11.8 [−17, −6.3] and −20.7 [−28.5, −12.8], respectively). Similar results were obtained with clopidogrel 150 mg. Ticagrelor 90 mg twice daily was associated with lower PRU (−42.5 [−62.9, −21.9]), lower PRI (−9.3 [−15.6, −3.5]), and lower MPA (−8.9 [−16.4, −1.2]) compared with prasugrel 10 mg. In conclusion, our meta-analysis suggests that ticagrelor achieved significantly lower on-treatment PR compared with prasugrel, with both being superior to clopidogrel standard or high dose.

Fish oil supplementation (FOS) is known to have cardiovascular benefits. However, the effects of FOS on thrombosis are incompletely understood. We sought to determine if the use of FOS is associated with lower indices of atherothrombotic risk in patients with suspected coronary artery disease (sCAD). This is a subgroup analysis of consecutive patients with sCAD (n = 600) enrolled in the Multi-Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis study. Patients on FOS were compared with patients not on FOS. Lipid profile was determined by vertical density gradient ultracentrifugation (n = 520), eicosapentaenoic acid + docosahexaenoic acid was measured by gas chromatography (n = 437), and AtherOx testing was performed by immunoassay (n = 343). Thromboelastography (n = 419), ADP- and collagen-induced platelet aggregation (n = 137), and urinary 11-dehydrothromboxane B2 levels (n = 259) were performed immediately before elective coronary angiography. In the total population, FOS was associated with higher eicosapentaenoic acid + docosahexaenoic acid content (p <0.001), lower triglycerides (p = 0.04), total very low–density lipoprotein cholesterol (p = 0.002), intermediate-density lipoprotein cholesterol (p = 0.02), and AtherOx levels (p = 0.02) but not in patients on lipid-lowering therapy. Patients not on lipid-lowering therapy taking FOS had lower very low–density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, remnant lipoproteins, triglycerides, low-density lipoprotein cholesterol, AtherOx levels, collagen-induced platelet aggregation, thrombin-induced platelet-fibrin clot strength, and shear elasticity (p <0.03 for all). In clopidogrel-treated patients, there was no difference in ADP-induced aggregation between FOS groups. Patients on FOS had lower urinary 11-dehydrothromboxane B2 levels regardless of lipid-lowering therapy (p <0.04). In conclusion, the findings of this study support the potential benefit of FOS for atherothrombotic risk reduction in sCAD with the greatest benefit in patients not receiving lipid-lowering therapy. Future prospective studies to compare FOS with lipid-lowering therapy and to assess the independent effects of FOS on thrombogenicity are needed.

High platelet reactivity (HPR) during aspirin and clopidogrel therapy in patients with diabetes has been reported and may affect outcomes. However, the relation of platelet reactivity to glycemic control is less studied in patients on dual antiplatelet therapy. Platelet aggregation (PA) in response to 5 and 20 μmol/L adenosine diphosphate (ADP) was compared in type 2 diabetic (n = 36) and nondiabetic patients (n = 35) undergoing elective stenting on aspirin and clopidogrel maintenance therapy. The relation of glycosylated hemoglobin (HbA 1c) <7 g/dL (n = 16) and HbA 1c ≥7 g/dL (n = 20) on PA was examined. High platelet reactivity was defined as >46% for 5 μmol/L ADP-induced and >59% for 20 μmol/L ADP-induced PA. Diabetic patients had higher 5 and 20 μmol/L ADP-induced PA than nondiabetic patients (45 ± 17 vs 33 ± 12, P = .009 and 52 ± 19 vs 40 ± 12, P = .004, respectively). Diabetic patients with HbA 1c ≥7.0 g/dL had significantly higher 5 and 20 μmol/L ADP-induced PA versus patients with diabetes with HbA 1c <7.0 g/dL (54 ± 15 vs 34 ± 14, P < .001 and 62 ± 14 vs 40 ± 17, P < .001, respectively). Among diabetic patients with HbA 1c ≥7 g/dL, the prevalence of HPR was 65% and 60%; and among diabetic patients with HbA 1c <7 g/dL, the prevalence of HPR was 19% and 13% as measured by 5 and 20 μmol/L ADP-induced PA, respectively. A correlation was present between 5 and 20 μmol/L ADP-induced PA and HbA 1c ( r = 0.60 and 0.62, P = .0001, respectively). An important relation exists between glycemic control and platelet reactivity in patients with type 2 diabetes mellitus treated with dual antiplatelet therapy. Poorly controlled patients with diabetes have the greatest platelet reactivity and may require alternative antiplatelet strategies, and further clinical investigations are warranted.