Adequate Aspirin Research Articles

The 15-Epilipoxin-A4 Pathway with Prophylactic Aspirin in Preventing Preeclampsia: A Longitudinal Cohort Study.

The benefit of aspirin in preventing preeclampsia is increasingly recognized; however, its mechanism of action remains unclear. Nonobstetric studies have described an anti-inflammatory effect of aspirin through the 15-epilipoxin-A4 pathway (aspirin-triggered lipoxin [ATL]). However, the anti-inflammatory mechanism of aspirin in the prevention of preeclampsia remains unknown. To examine (1) the difference in longitudinal endogenous lipoxin-A4 (En-Lipoxin-A4) concentration in low-risk (LR) and high-risk (HR) pregnancies, and (2) the effect of aspirin on endogenous ATL concentration and the associated effect on cytokine profile of HR women. Plasma from 220 HR women was collected at 12, 16, 20, 24, 28, 32, and 36 weeks of gestation. Adherence to aspirin was biochemically verified. Plasma En-Lipoxin-A4 and ATL concentrations were analyzed using liquid chromatography mass spectrometry, and cytokines, interleukin (IL)-10, tumor necrosis factor-α, interferon-γ, IL-8, and IL-1β, with the high-sensitivity multibead Luminex® assay. HR women have up to 70% lower plasma concentration of En-Lipoxin-A4 (P < 0.001) than LR women. HR women with adequate aspirin adherence (HR-AA) (n = 82) had higher plasma concentration of ATL (P < .001), lower concentration of IL-8 from 16 to 36 weeks of gestation (P < .001), and increased IL-10 concentration from 16 to 28 weeks of gestation (P = .03) compared with high-risk women who were not on aspirin (HR-NA). HR-AA who did not develop preeclampsia had higher plasma En-lipoxin-A4 (P < .001), ATL (P = .02), and IL-10 concentrations (P < .001) with lower IL-8 concentration (P = .004) than HR women who developed preeclampsia. Plasma concentration of En-Lipoxin-A4 is lower in HR women than in LR controls. Adequate adherence with aspirin results in an increase in ATL and IL-10 with reduced IL-8 plasma concentration. This study suggests a potential anti-inflammatory role of aspirin through the ATL pathway with prophylactic aspirin in HR pregnant women.

Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of Statins in High‐Risk Patients for Cardiovascular Disease

We studied the influence of cardiovascular (CV) risk factors, previous CV events, and cotreatments with preventive medicines, on residual platelet thromboxane (TX)B2 production in 182 patients chronically treated with enteric coated (EC)-aspirin (100 mg/day). The response to aspirin was also verified by assessing arachidonic acid-induced platelet aggregation and urinary 11-dehydro-TXB2 levels. Residual serum TXB2 levels exceeded the upper limit value for an adequate aspirin response in 14% of individuals. This phenomenon was detected at 12 hours after dosing with aspirin. The coadministration of statins (mostly atorvastatin) was an independent predictor of residual serum TXB2 levels, and the percentage of patients with enhanced values was significantly lower in statin users vs. nonusers. We provide evidence in vitro that atorvastatin reduced residual TXB2 generation by increasing the extent of acetylation of platelet COX-1 by aspirin. In conclusion, the coadministration of statins may counter the mechanisms associated with reduced bioavailability of aspirin detected in some individuals with CV disease.

The Effect of Xuefuzhuyu Oral Liquid on Aspirin Resistance and Its Association with rs5911, rs5787, and rs3842788 Gene Polymorphisms.

Aspirin should be continued indefinitely in patients after interventional therapy, but 10% to 40% of patients experience recurrent vascular events despite adequate aspirin therapy, a condition known as aspirin resistance (AR). Xuefuzhuyu oral liquid, derived from the classic recipe Xuefuzhuyu decoction, has been well documented to inhibit platelet aggregation and to improve hemorheology. The aims of this study were to investigate the effects of Xuefuzhuyu oral liquid on AR in patients with chronic stable angina after percutaneous coronary intervention (PCI) and the possible genetic markers related to the drug response. 43 patients diagnosed as having aspirin resistance or semi-resistance were randomly divided into control and treatment groups after screening 207 stable CHD patients. Platelet aggregation rate was determined using turbidimetry. Three single nucleotide polymorphisms in COX-1 (rs5787, rs3842788) and GP IIb (rs5911) were genotyped in whole blood samples using ABI PRISM 7900 HT Fast Real-Time instrument and ABI PRISM 3730 DNA Sequencer. The results showed that Xuefuzhuyu oral liquid could effectively improve blood stasis syndrome and AR by inhibiting ADP-induced platelet aggregation and that patients with the rs5911 genetic variant exhibited better drug response upon treatment with Xuefuzhuyu oral liquid, which suggests Xuefuzhuyu oral liquid as a new possible drug for the prevention of AR.

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639).

Individual variability in the response to aspirin, has been established by various platelet function assays, however, the clinical relevance of aspirin resistance (AR) in patients undergoing coronary artery bypass grafting (CABG) has to be evaluated. Our working group conducted a randomized controlled trial (NCT01159639) with the aim to assess impact of dual antiplatelet therapy (APT) on outcomes among patients with AR following CABG. Patients that were aspirin resistant on fourth postoperative day (POD 4) were randomly assigned to receive either dual APT with clopidogrel (75 mg) plus aspirin (300 mg)-intervention arm or monotherapy with aspirin (300 mg)-control arm. This exploratory analysis compares clinical outcomes between aspirin resistant patients allocated to control arm and patients that have had adequate platelet inhibitory response to aspirin at POD 4. Both groups were treated with 300 mg of aspirin per day following surgery. We sought to evaluate the impact of early postoperative AR on outcomes among patients following CABG. Exploratory analysis included a total number of 325 patients. Of those, 215 patients with adequate response to aspirin and 110 patients with AR allocated to aspirin monotherapy following randomization protocol. The primary efficacy end point (MACCEs-major adverse cardiac and cardiovascular events) occurred in 10 and 6 % of patients with AR and with adequate aspirin response, respectively (p = 0.27). Non-significant differences were observed in bleeding events occurrence. Subgroup analysis of the primary end point revealed that aspirin resistant patients with BMI > 30 kg/m(2) tend to have a higher occurrence of MACCEs 18 versus 5 % (relative risk 0.44 [95 % CI 0.16-1.16]; p = 0.05). This exploratory analysis did not reveal significant impact of aspirin resistance on outcomes among patients undergoing CABG. Further, sufficiently powered studies are needed in order to evaluate clinical relevance of AR in patients undergoing CABG.

Fatty acids and TxA2 generation, in the absence of platelet-COX-1 activity

Background and aimsOmega-3 fatty acids suppress Thromboxane A2 (TxA2) generation via mechanisms independent to that of aspirin therapy. We sought to evaluate whether baseline omega-3 fatty acid levels influence arachidonic acid proven platelet-cyclooxygenase-1 (COX-1) independent TxA2 generation (TxA2 generation despite adequate aspirin use). Methods and resultsSubjects with acute myocardial infarction, stable CVD or at high risk for CVD, on adequate aspirin therapy were included in this study. Adequate aspirin action was defined as complete inhibition of platelet-COX-1 activity as assessed by <10% change in light transmission aggregometry to ≥1 mmol/L arachidonic acid. TxA2 production was measured via liquid chromatography–tandem mass spectrometry for the stable TxA2 metabolite 11-dehydro-thromboxane B2 (UTxB2) in urine. The relationship between baseline fatty acids, demographics and UTxB2 were evaluated. Baseline omega-3 fatty acid levels were not associated with UTxB2 concentration. However, smoking was associated with UTxB2 in this study. ConclusionBaseline omega-3 fatty acid levels do not influence TxA2 generation in patients with or at high risk for CVD receiving adequate aspirin therapy. The association of smoking and TxA2 generation, in the absence of platelet COX-1 activity, among aspirin treated patients warrants further study.

Optimization of antiaggregant therapy in rheumatoid arthritis and coronary heart disease patients receiving nonsteroidal anti-inflammatory drugs

Objective: to study coagulative and vascular-thrombocytic hemostases in patients with rheumatoid arthritis (RA) and coronary heart disease (CHD) depending on therapy with different nonsteroidal anti-inflammatory drugs (NSAIDs) alone and in combination with low-dose aspirin. Subjects and methods. The trial enrolled 58 patients (43 women and 15 men) with a valid diagnosis of RA. The patients' mean age was 61.2 years; the disease duration averaged 10 years. All the patients received therapy with disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. All had CHD; 52 of the 58 patients presented with arterial hypertension; 30 had noncoronary atherosclerosis. Cardiovascular diseases were first identified in 18 patients. All took heart medications. Coagulative and vascular-thrombocytic hemostases were studied in all the patients and the results were compared depending on to the taken NSAID (diclofenac, tenoxicam, nimesulide, meloxicam). Thirty-seven patients who had not previously received antiaggregant therapy were given aspirin in a dose of 100 mg when they were found to have platelet hyperaggregation and aggregation was restudied on aspirin therapy days 7-8. A control group consisted of 26 healthy men (mean age 55 years) who received no medications. Results. In patients with RA and CHD, activated coagulative hemostasis was identified in 65.5% of cases. The signs of hypercoagulation were observed in 35 of the 58 patients. When different NSAIDs were used, the coagulative hemostatic changes were unidirectional and no statistically significant differences were found between the groups. The patients taking diclofenac, nimesulide, or meloxicam were found to have activated vascular-thrombocytic hemostasis. Those receiving tenoxicam showed a tendency towards decreased adrenaline-induced platelet aggregation (the drug's aspirin-like effect); however, no statistical processing was made because of few cases. The use of aspirin in the patients taking diclofenac, nimesulide, or meloxicam resulted in lower platelet aggregation in the vast majority of cases despite NSAID intake. No adequate aspirin response was obtained in 32.4% of the patients. Conclusion. Aspirin is indicated in RA and CHD patients receiving NSAIDS. Antiaggregant therapy should be used under control of vascular-thrombotyc hemostasis as aspirin is insufficiently effective in one third of cases in this group.

Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.