Chronic Aspirin Treatment Research Articles

Kinetics of Circulating Extracellular Vesicles Over the 24-Hour Dosing Interval After Low-Dose Aspirin Administration in Patients atCardiovascular Risk.

Extracellular vesicles (EVs) are small vesicles deriving from all cell types during cell activation, involved in transcellular communication, and regarded as predictors of vascular damage and of cardiovascular events. We tested the hypothesis that, in patients on chronic low-dose aspirin treatment for cardiovascular prevention, aspirin may affect the release of EVs within the 24-hour interval. We enrolled 84 patients, mostly at high or very high cardiovascular risk, on chronic low-dose aspirin treatment. The numbers of circulating EVs (cEVs) and annexinV+ cEVs (total, platelet-derived, endothelial-derived, and leucocyte-derived) were assessed immediately before, and after 10 and 24 hours of a witnessed aspirin administration. Platelet cyclooxygenase 1 (COX-1) recovery was characterized by measuring serum thromboxane B2 (sTXB2 ) at the same timepoints. Nine healthy participants were also enrolled. In patients, daily aspirin administration acutely inhibited after 10 hours following aspirin administrations the release of cEVs (total and leukocyte-derived) and annexinV+ cEVs (total, platelet-derived, endothelial-derived, and leukocyte-derived), with a rapid recovery at 24 hours. The inhibition after 10 hours suggests a COX-1-dependent mechanism. Interestingly, the slope of platelet-derived and of annexinV+ platelet-derived cEVs were both directly related to sTXB2 slope and COX-1 messenger RNA, raising the hypothesis that vice versa, cEVs may affect the rate of COX-1 recovery and the subsequent duration of aspirin effect. In healthy participants, no circadian difference was observed, except for leukocyte-derived cEVs. Our findings suggest a previously unappreciated effect of aspirin on the kinetics of a subset of cEVs possibly contributing to the cardioprotective effects of this drug.

Low-Dose Aspirin Augments the Anti-Inflammatory Effects of Low-Dose Lithium in Lipopolysaccharide-Treated Rats.

Mounting evidence suggests that immune-system dysfunction and inflammation play a role in the pathophysiology and treatment of mood-disorders in general and of bipolar disorder in particular. The current study examined the effects of chronic low-dose aspirin and low-dose lithium (Li) treatment on plasma and brain interleukin-6 and tumor necrosis factor-α production in lipopolysaccharide (LPS)-treated rats. Rats were fed regular or Li-containing food (0.1%) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. On days 21 and 42 rats were injected with 1 mg/kg LPS or saline. Two h later body temperature was measured and rats were sacrificed. Blood samples, the frontal-cortex, hippocampus, and the hypothalamus were extracted. To assess the therapeutic potential of the combined treatment, rats were administered the same Li + aspirin protocol without LPS. We found that the chronic combined treatment attenuated LPS-induced hypothermia and significantly reduced plasma and brain cytokine level elevation, implicating the potential neuroinflammatory diminution purportedly present among the mentally ill. The combined treatment also significantly decreased immobility time and increased struggling time in the forced swim test, suggestive of an antidepressant-like effect. This preclinical evidence provides a potential approach for treating inflammation-related mental illness.

Effects of chronic low-dose aspirin treatment on tumor prevention in three mouse models of intestinal tumorigenesis.

Although early detection and treatment of colorectal cancer (CRC) have improved, it remains a significant health‐care problem with high morbidity and mortality. Data indicate that long‐term intake of low‐dose aspirin reduces the risk of CRC; however, the mechanisms underlying this chemopreventive effect are still unclear. Different mouse models for inflammation‐associated, sporadic, and hereditary CRC were applied to assess the efficacy and mechanism of low‐dose aspirin on tumor prevention. An initial dosing study performed in healthy mice indicates that aspirin at a dose of 25 mg/kg/d has a similar pharmacodynamic effect as low‐dose aspirin treatment in human subjects (100 mg/d). Chronic low‐dose aspirin treatment suppresses colitis‐associated and to a lesser extent spontaneous tumorigenesis in mice. Aspirin's antitumor effect is most pronounced in a preventive approach when aspirin administration starts before the tumor‐initiating genotoxic event and continues for the duration of the experiment. These effects are not associated with alterations in cell proliferation, apoptosis, or activation of signaling pathways involved in CRC. Aspirin‐induced reduction in tumor burden is accompanied by inhibition of thromboxane B2 formation, indicating reduced platelet activation. Aspirin treatment also results in decreased colonic prostaglandin E2 formation and tumor angiogenesis. With respect to colitis‐triggered tumorigenesis, aspirin administration is associated with a reduction in inflammatory activity in the colon, as indicated by decreased levels of pro‐inflammatory mediators, and tumor‐associated iNOS‐positive macrophages. Our results suggest that low‐dose aspirin represents an effective antitumor agent in the context of colon tumorigenesis primarily due to its well‐established cyclooxygenase inhibition effects.

Hyperglycaemia is associated with cancer-related but not non-cancer-related deaths: evidence from the IPC cohort.

Hyperglycaemia has been associated with the incidence of all and specific types of cancer, distinct from the risks related to diabetes. The relationships between blood glucose and mortality rates related to all and specific cancers were analysed in comparison with all-cause or non-cancer-related mortality rates in a large, general primary care population in France. Between January 1991 and December 2008, 301,948 participants (193,221 men and 108,727 women), aged 16-95years (mean ± SD 44.8 ± 12.0years for men and 45.1 ± 14.2years for women), had a health check at the IPC Centre. All data collected in standard conditions during the health checks-up were used for statistical analysis All examinations were performed under fasting conditions and included a blood glucose measurement. Participants with known diabetes (<9%) were excluded from the analysis. Participants were classified into quintiles based on their blood glucose measurement and were followed for a maximum of 17years (mean ± SD 9.2 ± 4.7years) to assess all-cause, cancer and non-cancer mortality rates. A non-linear relationship was observed between cancer mortality rates and blood glucose quintile after adjustment for age and sex. There was a significant association between the group with the highest blood glucose level and cancer-related death (multivariate Cox model, HR [95% CI] 1.17 [1.03, 1.34]), while the group with normoglycaemia showed no association with cancer-related deaths. We did not observe a relationship between blood glucose and all-cause or non-cancer mortality rates. An excess risk of death was observed in the highest blood glucose quintile for gastrointestinal cancer and leukaemia. Adjustments for diabetes and aspirin use did not modify the results. However, this excess risk disappeared with use of glucose-lowering agents (HR [95% CI] 1.03 [0.74, 1.43]). Hyperglycaemia is associated with significantly higher rates of cancer-related deaths, particularly in gastrointestinal cancer and leukaemia, but not with non-cancer-related deaths. The association is retained when taking into account confounding factors, including chronic aspirin treatment.

P4014In vitro inhibition of MRP4 mediated transport reduces HARPR in patients under chronic aspirin treatment

P4014In vitro inhibition of MRP4 mediated transport reduces HARPR in patients under chronic aspirin treatment

Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment.

Platelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA<1 month patients. Platelets obtained from ASA>2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1-independent mechanism.

The lack of aspirin resistance in patients with coronary artery disease.

BackgroundAspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated.MethodsOne hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR.ResultsIn 138 patients only acCOX1 was detected, in the remaining six patients nacCOX1 disappeared after a compliance period. AA induced TXB2 production by platelets was very low in all patients including the 6 patients after compliance. AA induced platelet aggregation, secretion and with a few exceptions the VerifyNow Assay also demonstrated the effect of aspirin. Smoking, diabetes mellitus and inflammatory conditions did not influence the results. The very low amount of COX2 mRNA detected in 39 % of the investigated platelets did not influence the effect of aspirin.ConclusionsNo aspirin resistance was detected among patients with stable coronary artery disease. COX2 expression in platelets did not influence the effect of aspirin.

MRP4 expression in platelet of patients under chronic aspirin treatment is influenced by microrna modulation

MRP4 expression in platelet of patients under chronic aspirin treatment is influenced by microrna modulation

Aspirin resistance in adult patients after Fontan surgery

BackgroundThrombotic complications are common in adult patients who have had a Fontan operation early in life for treatment of congenital heart disease. ObjectiveTo characterize platelet function and responsiveness to aspirin in relation to thrombogenesis, systemic inflammation, and markers of endothelial function in adults with Fontan circulation (FC). MethodsThirty-four FC patients (age 18–40years; 62% taking aspirin chronically and 38% not taking aspirin) and 32 age- and sex-matched healthy controls were studied. Platelet function was evaluated by measurement of basal concentrations of thromboxane B2 (TXB2) and sCD40L and ex-vivo generation of TXB2 and sCD40L. Plasma concentrations of thrombin–antithrombin, endothelin-1, vWF, IL-6, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 also were measured. ResultsPlatelet numbers were significantly lower in FC patients than in controls, but the patients had significantly higher platelet activity, as evidenced by higher TXB2 and sCD40L concentrations and higher ex vivo generation of TXB2. Chronic aspirin treatment had no effect on plasma concentrations of TXB2 and sCD40L in FC, but in 52% of aspirin-treated FC subjects, TXB2 concentrations remained elevated at 60min of TXB2 generation, indicating aspirin resistance. In addition, FC patients had increased levels of thrombin–antithrombin, endothelin-1, vWF, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 but not of IL-6. ConclusionAdults with FC had lower platelet numbers but increased platelet activity, increased thrombogenesis, systemic inflammation, and endothelial dysfunction. A significant proportion of aspirin-treated FC adults had aspirin resistance, which may be at least in part responsible for their increased incidence of thrombotic complications.

Antiplatelet resistance in outpatients with monitored adherence

Antiplatelet resistance with aspirin and clopidogrel has been associated with clinical, cellular and pharmacogenetic factors; and non-adherence has been considered as a major contributor to resistance in outpatients. We aimed at assessing factors to resistance when adherence to the antiplatelet drugs and all other oral solid drugs was controlled for. In a pilot study, we tested arachidonic acid and/or ADP-induced in vitro platelet aggregation of 82 outpatients with chronic aspirin and/or clopidogrel treatment before and after a one-week period of measuring the patient’s adherence with the polymedication electronic monitoring system (POEMS). Resistance was found in 20% (aspirin; n = 69) and 25% (clopidogrel; n = 32) of the patients after monitored adherence. Mean platelet aggregation was not (aspirin) or non-significantly (clopidogrel) lowered when compared to baseline. Diabetes mellitus and inflammation were consistently associated with resistance to both drugs, but CYP2C19 polymorphisms could not be confirmed as predictors of clopidogrel response. Electronically compiled multidrug dosing histories allowed the concomitant intake of high-dose lipophilic statins to be identified as a risk factor of impaired response to clopidogrel and revealed that exposure to further potential drug–drug interactions (DDIs) was too low for analysis. Multidrug adherence monitoring allowed thus dismissing non-adherence as a major contributor to resistance and inter-individual response variability in an outpatient setting. Additionally, it allowed analysing the impact of DDIs according to the actual exposure to the potentially interfering drugs. Further studies based on this methodology are essential to prevent misleading results due to incomplete adherence and gain additional insight into the impact of timing adherence on antiplatelet drug response.

The administration of a loading dose of aspirin to patients presenting with acute myocardial infarction while receiving chronic aspirin treatment reduces thromboxane A2-dependent platelet reactivity

The optimal dose of aspirin for patients presenting with acute myocardial infarction (AMI) while receiving chronic aspirin therapy has not been clearly established. We evaluated whether continued treatment with 100 mg of aspirin or a loading dose (200–500 mg) influences thromboxane A2 (TX) suppression or platelet reactivity. Sixty-four consecutive patients with AMI and 98 healthy subjects (82 aspirin-free and 16 receiving 100 mg daily for a week) were evaluated. Treatment was at the discretion of the attending physician. Collagen (1 µg/ml)-induced TX synthesis, 14C-serotonin-release, platelet aggregation, and the PFA-100 assay were evaluated. The platelet TX synthesis of patients receiving a loading dose of aspirin was sixfold lower than that of patients receiving 100 mg of aspirin (p < 0.005). This was associated with marked reductions in 14C-serotonin-release and arachidonic-acid-induced aggregation and an increase in the PFA-100 closure time (p < 0.01). Categorization of patients according to their TX synthesis (<95% or ≥95% inhibition vs. healthy aspirin-free subjects) revealed that 8% of the patients treated with loading doses had a poor response (<95% inhibition) vs. 53% of those treated with 100 mg (p < 0.001). Patients with lower TX inhibition had higher serum NT-Pro-BNP (p < 0.005), a marker of poor left ventricular systolic function. Administration of a loading dose of aspirin to patients with AMI during existing chronic aspirin treatment induced greater reductions in platelet TX synthesis and TX-dependent platelet reactivity than the continued treatment alone.

Antithrombotic drugs and risk of hemorrhagic stroke in the general population

To investigate the relationship between hemorrhagic stroke and use of antiplatelets and warfarin using data from The Health Improvement Network. A total of 1,797 incident cases of intracerebral hemorrhage (ICH) and 1,340 of subarachnoid hemorrhage (SAH) were ascertained. Density-based sampling was used to select 10,000 controls free from hemorrhagic stroke. Risk of hemorrhagic stroke was evaluated in current users and nonusers of antiplatelets and warfarin. Unconditional logistic regression models were used to adjust for age, sex, calendar year, alcohol, body mass index, hypertension, and health services utilization. Aspirin use was not associated with an increased risk of ICH (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.93-1.21), but was associated with a decreased risk of SAH (OR 0.82, 95% CI 0.67-1.00), compared with no therapy. Aspirin use ≥3 years was associated with a decreased risk of SAH (OR 0.63, 95% CI 0.45-0.90) compared with no therapy. Warfarin use was associated with a greatly increased risk of ICH (OR 2.82, 95% CI 2.26-3.53) and a moderately increased risk of SAH (OR 1.67, 95% CI 1.15-2.43) compared with no therapy. International normalized ratio values ≥3 carried a marked risk of ICH (OR 7.01, 95% CI 4.10-11.99). Aspirin is not associated with a risk of ICH compared with no therapy. Chronic low-dose aspirin treatment may have a protective effect on the risk of SAH. Warfarin users in this study cohort were at a much higher risk of ICH than those receiving no therapy, with a marked association with international normalized ratio >3.

Chronic aspirin via dose-dependent and selective inhibition of cardiac proteasome possibly contributed a potential risk to the ischemic heart

Impaired cardiac proteasome has been reported in ischemic heart and heart failure. Recent data highlighted aspirin as an inhibitor of the ubiquitin-proteasome system, however, it's unclear whether it affects cardiac proteasome functions. Myocardial infarction (MI), sham or normal male SD rats were injected intraperitoneally with high (300mg/kg), low (5mg/kg) aspirin or saline (control) once a day for seven weeks. Parallel experiments were performed in the hypoxia/reoxygenated human ventricular myocytes. Dose-related increases in heart and ventricular weight, and impaired cardiac functions, were found more exacerbated in the aspirin-treated MI rat hearts than the saline-treated MI counterparts. The activity of 26S, 20S and 19S declined by about 30%, or the 20S proteasome subunits β5, β2 and β1 decreased by 40%, 20% and 30%, respectively, in the MI rats compared with the non-MI rats (P<0.05). Compared with the saline-treated MI rats, 26S and 20S in high or low dose aspirin-treated MI rats further decreased by 30% and 20%, β5 by 30% and 12%, and β1 by 40% and 30%, respectively, and the lost activity was correlated with the compromised cardiac functions or the decreased cell viability. The dose-related and selective inhibition of 26S and 20S proteasome, or the 20S proteasome subunits β5 and β1 by aspirin was comparable to their protein expressions in the MI rats and in the cultured cells. The impaired cardiac proteasome, enhanced by chronic aspirin treatment, attenuated the removal of oxidative and ubiquitinated proteins, and chronic aspirin treatment via selective and dose-dependent inhibition of cardiac proteasome possibly constituted a potential risk to ischemic heart.

C0231 Patients presenting with an acute coronary syndrome while on chronic aspirin treatment: Do they require a loading dose of aspirin?

C0231 Patients presenting with an acute coronary syndrome while on chronic aspirin treatment: Do they require a loading dose of aspirin?

EV-077 in vitro inhibits platelet aggregation in type-2 diabetics on aspirin

IntroductionThis study aimed to characterize the in vitro effect of EV-077, a compound that antagonises the binding of prostanoids and isoprostanes to the thromboxane receptor (TP) and inhibits the thromboxane synthase (TS), on platelet aggregation of patients with type-2 diabetes and coronary artery disease (CAD) on chronic aspirin treatment. The effect of EV-077 on 8-iso-PGE2-mediated TP receptor contraction of human arteries was also investigated. Materials and MethodsFifty-two type-2 diabetics with CAD on chronic aspirin (100mg) treatment were studied. Arachidonic acid-induced platelet aggregation was measured by impedance aggregometry in platelet-rich plasma (PRP) and whole blood anticoagulated with hirudin, and by light transmission aggregometry in citrate-anticoagulated PRP following 10-min in vitro exposure to EV-077 (100nmol/l) or control. The effect of EV-077 was measured on isometric contraction of 24 human umbilical arteries induced by isoprostane 8-iso-PGE2. ResultsArachidonic acid (1mmol/l) induced substantial aggregation in hirudin-anticoagulated whole blood (63±4AU), which was significantly reduced by in vitro exposure to EV-077 (38±3AU, P<0.001). Virtually no arachidonic acid-induced aggregation in citrate-anticoagulated or hirudin-anticoagulated PRP was observed. EV-077 potently, competitively and reversibly inhibited TP mediated contraction of umbilical arteries by 8-iso-PGE2 (P<0.01). ConclusionsAspirin did not completely inhibit arachidonic acid-induced platelet aggregation in whole blood from type-2 diabetics with CAD. This aggregation is likely induced by prostanoids and/or isoprostanes produced by leukocytes, because it was significantly reduced by EV-077. The TP receptor-mediated contraction of human arteries induced by isoprostane 8-iso-PGE2 was effectively inhibited by EV-077.

Abstract 308: Chronic Aspirin Treatment Possibly Poses a Risk to Ischemic Heart via Impairment of Cardiac Proteasome Functions

Background: Impaired cardiac proteasome (CP) has been reported in ischemia and heart failure. Recent data highlighted aspirin as an inhibitor of the ubiquitin-proteasome system, however, it’s unclear whether it affects CP functions. Objective: We investigated the influence of aspirin on CP in the rat model of myocardial infarction (MI). Methods and Results: MI, sham or normal male SD rats were injected intraperitoneally with high (300mg/kg), low (5mg/kg) aspirin or saline (control) once a day for seven weeks. Parallel experiments were performed in the hypoxia/reoxygenated cell model of primary human ventricular myocytes incubated with different concentrations of aspirin. Myocardial hypertrophy, cardiac function, cell viability and the functions of 26S, 20S and 19S, including the β1, β2 and β5 subunits of 20S were determined. The activity of 26S, 20S and 19S declined by about 30%, and β5, β2 and β1 by 40%, 20% and 30%, respectively, in the MI rats compared with the non-MI rats ( P &lt;0.05). Compared with the saline-treated MI rats, 26S and 20S in high or low dose aspirin-treated MI rats further decreased by 30% and 20%, and β5 further decreased by 30% and 12%, and β1 by 40% and 30%, respectively, and their lost activity was correlated with compromised cardiac function in the MI rats. The dose-related and selective inhibition of β5 and β1 by aspirin was comparable to their protein expressions in the MI rats and in the cultured cells. However, the CP in the normal settings, or 19S and β2 in all the groups of animals or cultured cells were less affected by aspirin treatment. The impaired CP, dose-dependently enhanced by aspirin, led to the elevation of oxidative and ubiquitinated proteins in the MI rat hearts or in the hypoxia/reoxygenated cells. These aberrant proteins in turn constituted the ultimate causal factor for the cardiac dysfunction and the loss of cell viability. In vitro experiments confirmed that the purified CP from the MI rats or hypoxic cells, but was more susceptible to aspirin treatment, whereas the complexes in the normal settings appeared less affected by aspirin. Conclusions: Chronic aspirin treatment, via the dose-dependent and selective inhibition of CP, enhanced the ischemic CP dysfunction, which constitutes a potential risk factor for the ischemic heart.

Optimal drug therapy after aspirin-induced upper gastrointestinal bleeding

Upper gastrointestinal bleeding is a common adverse effect of chronic aspirin treatment. Traditionally, most physicians might tend to discontinue aspirin therapy after related gastrointestinal bleeding. However, recent studies have shown that continuation of aspirin is beneficial because of a decrease of cardiovascular complications and only a relatively small increase of recurrent peptic ulcer bleeding when combined with a proton pump inhibitor. There might be individual cases where the burden of recurrent gastrointestinal complications outweighs the risk of vascular events. In these cases the physician needs to carefully consider other precipitating factors for the recurrent gastrointestinal symptoms. At the moment, alternative antiplatelet therapy does not lead to lower gastrointestinal risks. In the near future, therapies with a more favorable profile might emerge.

Effect of chronic kidney disease on platelet reactivity to dual-antiplatelet therapy in patients treated with drug-eluting stents

We investigated the effect of chronic kidney disease (CKD) on platelet function in patients receiving dual-antiplatelet therapy after drug-eluting stent (DES) implantation. We examined 19 patients with CKD and 18 patients without CKD who underwent percutaneous coronary intervention (PCI) with DES. All of the patients had been on chronic aspirin treatment. Blood samples were obtained 20-24 h after a loading dose (300 mg) of clopidogrel. Platelet function was evaluated by measuring the closure time (CT) of a collagen/epinephrine (CEPI) or collagen/adenosine diphosphate (CADP) cartridge in the PFA-100 system. Maximum aggregation of agonist (epinephrine, ADP, collagen, or ristocetin)-induced platelet aggregation was also examined by light transmittance aggregometry. The frequency of the poor responders among CKD (n = 9, 47.4%) patients was significantly higher than that among non-CKD patients (n = 2, 11.1%, P = 0.016) as assessed using a CEPI-CT cartridge. Multiple logistic regression analysis revealed that CKD (odds ratio 7.39, 95% confidence interval 1.38-62.09, P = 0.0183] was the only independent determinant of the poor responders. There were no significant differences between the two groups in the value of CADP-CT or in maximum aggregation of epinephrine-, ADP-, collagen-, and ristocetin-induced platelet aggregation. Compared with non-CKD patients, CKD patients had lower response to aspirin therapy as assessed by the PFA-100 system with a CEPI cartridge. On the other hand, the platelet response to dual-antiplatelet therapy was not different between CKD and non-CKD patients.

Anticoagulant or aspirin treatment does not affect the positive predictive value of an immunological fecal occult blood test in patients undergoing colorectal cancer screening

The immunochemical fecal occult blood test (i-FOBT) is widely used as a recommended screening strategy for colorectal cancer (CRC). A growing number of patients potentially targeted by CRC screening programs are on oral anticoagulant or chronic low-dose aspirin therapy, mainly for primary or secondary cardiovascular prophylaxis. This study aims at evaluating whether the use of these medications may impact on the diagnostic performances of i-FOBT for CRC screening. All i-FOBT-positive patients on anticoagulant or chronic low-dose aspirin therapy recorded in a regional mass screening program database were enrolled as cases. Control groups were derived from the same database and included drug-naive i-FOBT-positive patients, matched in a ratio of 1 : 2 for age (± 3 years of age), sex, date of colonoscopy, and practice site. Information about the use of medications was collected by cross-checking patients' interview before colonoscopy and data recorded in the provincial electronic registry of medical prescriptions. The positive predictive value of i-FOBT for significant neoplasia (high-risk adenoma and CRC) was calculated in the case and control groups. In a 2-year study period, 2376 patients were recorded in the regional database. Of these patients, 53 (2%) were on anticoagulation (control group of 106 patients) and 172 (6.6%) were on chronic low-dose aspirin treatment (control group of 344 patients). Significant neoplasia was detected in 15 (28.3%) patients on anticoagulants and in 37 (34.9%) corresponding controls (P=0.45). Significant neoplasia was detected in 50 (29.1%) patients on chronic low-dose aspirin and in 107 (31.1%) corresponding controls (P=0.64). The positive predictive value of i-FOBT for significant neoplasia is not affected by ongoing anticoagulant or chronic low-dose aspirin therapy. This finding suggests that there is no need to interrupt these treatments before i-FOBT for CRC screening.

The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel

BackgroundDifferent platelet function tests can be used to evaluate the degree of achieved platelet inhibition in patients treated with clopidogrel. The presence of CYP 2C19*2 polymorphism can reduce the formation of the active metabolite of clopidogrel, resulting in less platelet inhibition.Patients and MethodsPatients with symptomatic coronary artery disease, all on chronic single aspirin treatment were randomized to continue on aspirin or change to clopidogrel. In 219 randomly selected clopidogrel treated patients, platelet reactivity was evaluated by VASP-PRI determination and by use of VerifyNow P2Y12-PRU. The CYP 2C19*2 G/A polymorphism was further determined.ResultsThe total frequency of clopidogrel resistance was 29.0% by VASP-PRI and 31.6% by VerifyNow-PRU. The number of patients being hetero- and homozygous combined for the CYP 2C19*2 polymorphism (GA/AA) was 64 (29%). Platelet reactivity was significantly higher in patients with the polymorphism compared to wild-type patients (GG). VASP-PRI was 50.9% (SD19) in patients having the polymorphism compared to 38.3% (SD21) in patients with the GG genotype (p = 0.001). Correspondingly, the mean PRU was 165 (SD67) compared to 124 (SD69) (p < 0.001). The frequency of clopidogrel resistance in patients with the polymorphism was 32% compared to 16% in wild-type patients when defined by VASP-PRI (p = 0.006). When defined by PRU (VerifyNow), the corresponding frequencies were 53% and 22% (p < 0.001).ConclusionsClopidogrel treated patients with the CYP 2C19*2 polymorphism have significantly increased platelet reactivity compared to patients with the wild-type, evaluated with the VASP determination, and even more pronounced with the VerifyNow P2Y12 method.Trial RegistrationClinicalTrials.gov: NCT00222261