Chronic Aspirin Research Articles

Aspirin therapy for colorectal cancer prevention: The evidence

While the use of aspirin for primary prevention of cardiovascular disease (CVD) has been downplayed recently, its potential role in reducing the risk of certain cancers, most notably colorectal cancer (CRC), has remained of signicant interest.

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

Retraction Note to: Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites. Neurochem Res (2011) 36:139-45.

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation.

Tolerance of daily low-dose aspirin does not preclude aspirin-exacerbated respiratory disease

Tolerance of daily low-dose aspirin does not preclude aspirin-exacerbated respiratory disease

Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin.

BackgroundPneumonia is complicated by high rate of mortality and cardiovascular events (CVEs). The potential benefit of aspirin, which lowers platelet aggregation by inhibition of thromboxane A2 production, is still unclear. The aim of the study was to assess the impact of aspirin on mortality in patients with pneumonia.Methods and ResultsConsecutive patients admitted to the University‐Hospital Policlinico Umberto I (Rome, Italy) with community‐onset pneumonia were recruited and prospectively followed up until discharge or death. The primary end point was the occurrence of death up to 30 days after admission; the secondary end point was the intrahospital incidence of nonfatal myocardial infarction and ischemic stroke. One thousand and five patients (age, 74.7±15.1 years) were included in the study: 390 were receiving aspirin (100 mg/day) at the time of hospitalization, whereas 615 patients were aspirin free. During the follow‐up, 16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%; P<0.001) were aspirin nonusers. Overall, nonfatal CVEs occurred in 7% of patients, 8.3% in nonaspirin users, and 4.9% in aspirin users (odds ratio, 1.77; 95% confidence interval, 1.03 to 3.04; P=0.040). The Cox regression analysis showed that pneumonia severity index (PSI), severe sepsis, pleural effusion, and PaO2/FiO2 ratio <300 negatively influenced survival, whereas aspirin therapy was associated with improved survival. Compared to patients receiving aspirin, the propensity score adjusted analysis confirmed that patients not taking aspirin had a hazard ratio of 2.07 (1.08 to 3.98; P=0.029) for total mortality.ConclusionsThis study shows that chronic aspirin use is associated with lower mortality rate within 30 days after hospital admission in a large cohort of patients with pneumonia.

Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users : data from a prospective multicenter capsule endoscopy registry.

Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users : data from a prospective multicenter capsule endoscopy registry.

ASSA14-12-01 Long-term outcome of bare-metal stent implantation in patients with coronary artery stenosis

Objectives To evaluate the long-term effects of bare-metal stent (BMS) implantation in patients with coronary artery stenosis or occlusion lesions and with symptoms of angina pectoris. Methods 224 patients with serious stenosis (75% to 100%) of a native coronary artery presenting with symptoms of angina pectoris were enrolled from1 Mach, 2001 to 1 Mach, 2010. Among them there were 123 cases with hypertension (54.9%), 52 cases with diabetes mellitus (23.2%), 3 cases (1.3%) with old myocardial infarction and 32 cases (14.3%) with hyperlipidemia. 74 patients (33.0%) were smoker. The coronary angiography showed that the type 1 lesion characteristics were 95 cases (42.4%), type 2a lesion characteristics were 50 cases (22.3%), type 2b lesion characteristics were 46 cases (20.5%) and type 3 lesion characteristics were 33 cases (14.7%). Single coronary vessel lesion was 143 cases (63.8%), double coronary vessel lesions were 64 cases (28.6%) and three coronary vessel lesions were 17 (7.6%). BMS was implanted in the ischemia related coronary lesion. The diameter of the implanted stents was (3.16 ± 0.42) mm with length of (18.38 ± 6.15) mm. After the procedure of PCI recommended antiplatelet regimen included clopidogrel and aspirin for 2 months and followed by chronic aspirin therapy. All patients were followed for 24 to 157 months with an average of (93.50 ± 39.20) months. The main endpoint of follow-up was the occurrence of the first major adverse cardiac event (MACE), defined as death due to all cause, nonfatal recurrent myocardial infarction, and target lesion revascularisation (TLR) and target vessel revascularisation (TVR), heart failure with III class and over, very late thrombosis in stent and stroke. Results Complete clinical status was available in 224 patients to the end of follow-up. The combined cumulative MACE rate was 37.5% (84 cases) with an average of 4.81% per year. The number of death due to all cause was 32 cases (14.29%) with an average of 1.83% per year. The rate of TLR was 14.29% (32 cases) with an average of 1.83% per year. The rate of TVR was 6.25% (14 cases) with an average of 0.80% per year. The rate of heart failure with III class was 1.33% (3 cases). CABG was need in 2 cases (0.89%). The very late thrombosis in stent (1 case, 0.45%) presenting STEMI was very low. 2 case (0.89%) died to cerebral haemorrhage occurring within 24 month after the PCI. Conclusions It was the low incidence rate of MACE in the long-term follow-up for more than 2 years that BMS was used to treat unselective coronary artery stenosis lesions.

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.

Aspirin and clopidogrel resistance using the cone and plate(let) analyser in Indian patients with coronary artery disease

BackgroundResistance to antiplatelet drugs is a well-known entity. However, data for aspirin and clopidogrel resistance, and its clinical significance, in Indian patients are meagre.Aims and objectivesWe sought to determine the...

Perioperative cardiovascular complications versus perioperative bleeding in consecutive patients with known cardiac disease undergoing non-cardiac surgery. Focus on antithrombotic medication. The PRAGUE-14 registry.

BackgroundInterruption of antithrombotic treatment before surgery may prevent bleeding, but at the price of increasing cardiovascular complications. This prospective study analysed the impact of antithrombotic therapy interruption on outcomes in non-selected surgical patients with known cardiovascular disease (CVD).MethodsAll 1200 consecutive patients (age 74.2 ± 10.2 years) undergoing major non-cardiac surgery (37.4 % acute, 61.4 % elective) during a period of 2.5 years while having at least one CVD were enrolled. Details on medication, bleeding, cardiovascular complications and cause of death were registered.ResultsIn-hospital mortality was 3.9 % (versus 0.9 % mortality among 17,740 patients without CVD). Cardiovascular complications occurred in 91 (7.6 %) patients (with 37.4 % case fatality). Perioperative bleeding occurred in 160 (13.3 %) patients and was fatal in 2 (1.2 % case fatality). Multivariate analysis revealed age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia predictive of cardiovascular complications. For bleeding complications multivariate analysis found warfarin use in the last 3 days, history of hypertension and general anaesthesia as independent predictive factors. Aspirin interruption before surgery was not predictive for either cardiovascular or for bleeding complications.ConclusionsPerioperative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease are relatively rare, but once they occur, the case fatality is high. Perioperative bleeding complications are more frequent, but their case fatality is extremely low. Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery are not predictive for perioperative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns.

Aspirin reload before elective percutaneous coronary intervention: impact on serum thromboxane b2 and myocardial reperfusion indexes.

Microvascular obstruction seems to predict poor outcome in patients undergoing elective percutaneous coronary intervention (PCI), but the underlying mechanism is still unclear. We analyzed whether serum thromboxane B2, a stable metabolite of thromboxane A2, may be implicated in post-PCI microvascular obstruction. We enrolled 91 patients (74 males, 66±10 years) on chronic low-dose aspirin therapy (aspirin, 100 mg daily) scheduled for elective PCI and randomly assigned to receive aspirin reload (325 mg orally, n=46) or no reload (control group, n=45) ≥1 hour before elective PCI. Serum levels of thromboxane B2, reperfusion indexes (corrected Thrombolysis In Myocardial Infarction frame count and myocardial blush grade), and serum cardiac troponin I were assessed before and after PCI. Serum thromboxane B2 significantly increased after 120 minutes (P=0.0447) from PCI in control but not in aspirin reload group. After PCI, both groups showed a statistically significant reduction in corrected Thrombolysis In Myocardial Infarction frame count more evident in aspirin reload group (P=0.0023). Moreover, after PCI, 61% of patients allocated to aspirin reload and only 32% of patients allocated to control group reached normal microcirculatory reperfusion (myocardial blush grade=3); patients with myocardial blush grade=3 exhibited lower values of serum thromboxane B2 compared with those with myocardial blush grade <3 (P=0.05). Periprocedural cardiac troponin I significantly increased (F=3.64; P=0.01334) and correlated with serum thromboxane B2 (ρ=0.31; P=0.0413) in control but not in aspirin reload group. In addition, left ventricular ejection fraction significantly increased after PCI only in the aspirin reload group (P=0.0005). Aspirin loading dose before elective PCI improves myocardial reperfusion and injury indexes, suggesting a possible role of platelet thromboxane A2 in microvascular occlusion. http://www.clinicaltrials.gov. Unique identifier: NCT01374698.

Aspirin use and risk of atrial fibrillation in the Physicians' Health Study.

BackgroundInflammatory processes have been associated with an increased risk of atrial fibrillation (AF), potentially allowing for preventive therapy by anti‐inflammatory agents such as aspirin. However, the effect of chronic aspirin on the incidence of AF has not been evaluated in a prospective cohort followed for an extended period.Methods and ResultsThis study was comprised of a prospective cohort of 23 480 male participants of the Physicians' Health Study. Aspirin intake and covariates were estimated using self‐reported questionnaires. Incident AF was ascertained through yearly follow‐up questionnaires. Cox's regression, with adjustment for multiple covariates, was used to estimate relative risk of AF. Average age at baseline was 65.1±8.9 years. During a mean follow‐up of 10.0 years, 2820 cases of AF were reported. Age‐standardized incidence rates were 12.6, 11.1, 12.7, 11.3, 15.8, and 13.8/1000 person‐years for people reporting baseline aspirin intake of 0, <14 days per year, 14 to 30 days per year, 30 to 120 days per year, 121 to 180 days per year, and >180 days per year, respectively. Multivariable adjusted hazard ratios (95% confidence interval) for incident AF were 1.00 (reference), 0.88 (0.76 to 1.02), 0.93 (0.76 to 1.14), 0.96 (0.80 to 1.14), 1.07 (0.80 to 1.14), and 1.04 (0.94 to 1.15) across consecutive categories of aspirin intake. Analysis of the data using time‐varying Cox's regression model to update aspirin intake over time showed similar results.ConclusionsIn a large cohort of males followed for a long period, we did not find any association between aspirin use and incident AF.

Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry

To develop appropriate management strategies for patients who take low-dose aspirin, it is important to identify the risk factors for GI injury. However, few studies have described the risk factors for small-bowel injury in these patients. To investigate factors influencing the risk of small-bowel mucosal breaks in individuals taking continuous low-dose aspirin. Capsule endoscopy data were collected prospectively from 5 institutions. Yokohama City University Hospital and 4 other hospitals. A total of 205 patients receiving treatment with low-dose aspirin for over 3 months. Colonoscopic and upper GI endoscopy had been performed in all of the patients before the capsule endoscope evaluation. Risk factors for small-bowel mucosal breaks. Of the 198 patients (141 male; mean age 71.9 years) included in the final analysis, 114 (57.6%) had at least 1 mucosal break. Multivariate analysis identified protein pump inhibitor (PPI) use (OR 2.04; 95% confidence interval [CI], 1.05-3.97) and use of enteric-coated aspirin (OR 4.05; 95% CI, 1.49-11.0) as independent risk factors for the presence of mucosal breaks. Cross-sectional study. PPI use appears to increase the risk of small-bowel injury in patients who take continuous low-dose aspirin. Clinicians should be aware of this effect of PPIs; new strategies are needed to treat aspirin-induced gastroenteropathy.

Tu1243 Risk Factors for Small Bowel Mucosal Breaks in Chronic Low-Dose Aspirin Users: Data From a Prospective Multicenter Capsule Endoscopy Registry

Tu1243 Risk Factors for Small Bowel Mucosal Breaks in Chronic Low-Dose Aspirin Users: Data From a Prospective Multicenter Capsule Endoscopy Registry

Outcomes in patients undergoing nephrectomy for renal cancer on chronic anticoagulation therapy

AimsTo report our experience on surgical resection of renal tumors for patients with a history of chronic anticoagulation (ACT) or aspirin use. MethodsWe performed a retrospective analysis of 2473 patients who underwent surgery for renal tumors between 2005 and 2012. Prior to surgery, 172 were on chronic ACT and 695 on aspirin. Multivariable linear and logistic regression models were used to compare transfusion and overall complication rates between patients undergoing renal surgery who were on therapy to patients who were on aspirin and to patients with no therapy. ResultsCompared to no therapy and aspirin patients those on ACT were older (57.3 (IQR 48.4–66.10) vs 63.9, (IQR 57.3–71.5) vs 68.4, (IQR 60.4–73.5); p < 0.001), with a higher percentage having an ASA score of 3 or 4 (42.4 vs 57.9 vs 82.6%; p < 0.001), respectively. ACT patients had a higher 30-day transfusion rate, 22.7% vs 7.6% vs 6.9%, and 90-day complication rate, 17.4% vs 7.2% vs 7.3%, both p < 0.001. The median length of stay differed statistically between groups (p < 0.001), with a modest longer stay in the anticoagulation group (OR 1.11 SE 0.26; p < 0.001). Transfusion and complication rates for patients on therapy undergoing minimally invasive surgery vs open surgery were not statistically different. ConclusionsPatients on chronic ACT had higher transfusion and overall complication rates compared to patients on no treatment or on chronic aspirin. These findings did not correlate to clinical differences in length of stay or grade 3–5 complications.

Aspirin for Heart Failure

There is fading evidence that chronic aspirin therapy reduces cardiovascular morbidity or mortality.1,2 One large trial (The Second International Study of Infarct Survival:ISIS-2) performed 30 years ago showed that aspirin, at a dose of 162.5 mg/d given for just 28 days, reduced mortality compared with placebo after an acute myocardial infarction.3 This success has never been repeated. Although aspirin must have been discontinued at the end of the double-blind period of ISIS-2, the effect of this short course of aspirin persisted for 10 years.4 Thus, there is good evidence, in the era before statin therapy or primary angioplasty, that aspirin, given at this dose for this duration, is effective. There is no robust evidence that any other antiplatelet regimen, in terms of dose, agent, or duration, is superior; most subsequent studies having permitted the inclusion of patients receiving lower, nonevidence-based doses of aspirin.5–7 No substantial trial of long-term aspirin therapy for the primary or secondary prevention of cardiac events has ever confirmed this reduction in mortality. No long-term trial after myocardial infarction has ever even studied doses <300 mg/d.2 The results of meta-analyses have been driven by the ludicrously positive results of some small trials and the absence of small negative trials.1,8 This most likely reflects reporting and publication bias, which renders meta-analysis an intrinsically unreliable form of evidence that should be relegated to a method of confirming the results of an adequately powered, definitive trial or for generating hypotheses.9 Journal editors, unaware of their biases and the damage they might do, are only too willing to publish small implausibly positive results but reluctant …

Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial

IntroductionPerioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin...

Proximal predominance of small bowel injury associated with uncoated low-dose aspirin therapy

Only a limited number of studies have evaluated the small intestinal damage associated with chronic low-dose aspirin (LDA) therapy. We assessed, using capsule endoscopy, the prevalence and the characteristics of small bowel damage in chronic LDA users compared with patients taking an anticoagulant (AC) and those taking no antithrombotic drugs. We retrospectively reviewed 75 capsule endoscopy recordings from three groups of patients with unexplained iron-deficient anemia: 28 patients receiving LDA, 15 receiving an AC, and 32 not receiving any antithrombotic drug. The severity and location of small intestinal mucosal breaks were assessed in a blinded manner by two endoscopists. All LDA users received uncoated aspirin. The number of small bowel mucosal breaks in patients receiving LDA (median 1, extremes 0-125) was significantly higher than that in those taking an AC (0, 0-1) (P=0.0005) or no antithrombotic drugs (0, 0-23) (P<0.0001). The prevalence of patients with mucosal breaks was higher in the LDA group (71.4%) than in the AC group (20%, P=0.001) and the control group (12.5%, P=0.000005). Mucosal breaks in LDA users were predominant in the first tertile of the small bowel. The difference between groups was significant only for mucosal breaks located in the first tertile (P<0.0001). About two-thirds of uncoated LDA chronic users with anemia have mucosal breaks in the small bowel. These lesions are predominant in the proximal part, suggesting a topical toxic effect of uncoated LDA.

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.

Chronic low-dose aspirin use does not alter colonic mucosa in asymptomatic individuals: a prospective cross-sectional study (STROBE 1a)

ObjectivesAspirin may be involved in microscopic colitis (MC) development, but there are no data on colon histology in asymptomatic aspirin users. We prospectively assessed colonic and rectal mucosa from aspirin...