Chronic Low-dose Aspirin Users Research Articles

SIDE EFFECTS PROFILE OF ANTIPLATELET MEDICATION IN PATIENTS WITH CORONARY HEART DISEASE AT BHAYANGKARA HOSPITAL BALI-INDONESIA

Introduction: Coronary heart disease (CHD) is a disorder of heart function due to a lack of blood in the heart muscle due to narrowing of the coronary arteries. Antiplatelet in patients with CHD is a therapy that must be obtained by patients throughout their lives to prevent recurrent attacks and deaths from CHD. In the Province of Bali, especially in Denpasar, there is a lack of information about the type of side effects that occur on antiplatelet medication, so it is necessary to do a related study. Objective: The aim of this study is to identify the type of side effects that occur on antiplatelet medication in patients with CHD. Methods: A cross-sectional study involving 97 patients was done by observed the CHD patients treated with antiplatelet medication. Side effects were evaluate using Naranjo Algorithm. Patients were divided into three groups, including a low dose aspirin user group, clopidogrel user group, and aspirin-clopidogrel combination user group. Results: Antiplatelet side effects that occur in patients include headache (2.06%), diarrhea (1.03%), cyanosis (1.03%), gastrointestinal bleeding (8.25%), heartburn (11.34%), and nausea (6.19%). These side effects only occurred in 31.96% of the total subjects. The incidence of aspirin side effects was significantly greater than clopidogrel as well as aspirin-clopidogrel in combination (p <0.05). Conclusion: Patients with CHD who use antiplatelet agents in the long term to be more aware of the potential side effects that will occur, especially heartburn in chronic low-dose aspirin users.
 Keywords: Coronary Heart Disease, Side Effects, Antiplatelet, Aspirin, Clopidogrel

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy.

The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

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.

Identification of a high-risk group for low-dose aspirin-induced gastropathy by measuring serum pepsinogen in H. pylori-infected subjects.

We recently demonstrated in humans that the extent of low-dose aspirin (LDA)-induced gastropathy was directly related to the individual gastric acid secretion level. We also established reliable cutoff serum pepsinogen (PG) values to predict gastric acid secretion status. In this study, we investigated the clinical usefulness of measuring the serum pepsinogen values for identifying a high-risk group for gastric mucosal injury among chronic LDA users. One hundred long-term LDA users were enrolled in this analysis. Serum from each subject was subjected to determination of H. pylori status and measurement of pepsinogen values. According to our recent report, a PG I value ≥ 50 ng/mL was defined as estimated hyperchlorhydria in H. pylori-negative subjects, while a PG I/II ≥ 3.3 was defined as estimated hyperchlorhydria in H. pylori-positive subjects. The grade of gastric mucosal injury was assessed endoscopically, and multiple logistic regression analyses were used to estimate the risk. Estimated hyperchlorhydria was a strong independent risk for intensive gastric mucosal injury with an OR (95% CI): 34.0 (4.5-259) and for gastric ulcer with an OR (95% CI): 10.2 (1.8-58.3) in H. pylori-positive subjects, while it was not a significant risk in H. pylori-negative subjects. The association persisted even after excluding those with conventional risks for LDA-gastropathy such as ulcer histories. Using simple serum measurement of H. pylori antibody and pepsinogen concentrations, an extremely high-risk group for LDA-induced gastropathy could be extracted, and these patients should become a therapeutic target for prevention of LDA-induced gastropathy.

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

Small-bowel mucosal injuries in low-dose aspirin users with obscure gastrointestinal bleeding.

To investigate the clinical differences between small intestinal injuries in low-dose aspirin (LDA) users and in non-steroidal anti-inflammatory drug (NSAID) users who were examined by capsule endoscopy (CE) for obscure gastrointestinal bleeding (OGIB). A total of 181 patients who underwent CE for OGIB were included in this study. Based on clinical records, laboratory data such as hemoglobin levels, major symptoms, underlying diseases, the types and duration of LDA and NSAID use, and endoscopic characteristics of CE were reviewed. Out of a total of 45 cases of erosive lesions, 27 cases were taking LDA or NSAIDs (7 were on NSAIDs, 9 were on LDA alone, 9 were on LDA and thienopyridine, and 2 were on LDA and warfarin).The prevalence of ulcers or erosion during chronic use of LDA, LDA and the anti-platelet drug thienopyridine (clopidogrel or ticlopidine), and NSAIDs were 64.3%, 80.0%, and 75.0%, respectively. Erosive lesions were observed predominantly in chronic LDA users, while ulcerative lesions were detected mainly in NSAID users. However, concomitant use of thienopyridine such as clopidogrel with LDA increased the proportion of ulcers. The erosive lesions were located in the whole of the small intestine (jejunum and ileum), whereas ulcerative lesions were mainly observed in the ileum (P < 0.05). Our CE findings indicate that chronic LDA users and NSAID users show different types and locations of small-bowel mucosal injuries. The concomitant use of anti-platelet drugs with LDA tends to exacerbate the injuries from LDA-type to NSAID-type injuries.

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.

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...

Differences in the severity of small bowel mucosal injury based on the type of aspirin as evaluated by capsule endoscopy

BackgroundThe differences in the small intestinal toxicity of low-dose aspirin based on the type of aspirin used remains unclear. The purpose of this study was to evaluate the differences in the small bowel mucosal injury between buffered and enteric-coated aspirin users by capsule endoscopy. MethodsWe retrospectively reviewed the findings in chronic low-dose aspirin users (>3months) who underwent capsule endoscopy for the investigation of obscure gastrointestinal bleeding. The patients were classified into two groups based on the type of low-dose aspirin that they had been prescribed (enteric-coated aspirin group or buffered aspirin group), and evaluated the numbers of small bowel lesions and the Lewis score. ResultsCapsule-endoscopic findings of a total of 70 patients taking low-dose aspirin were reviewed. Significant differences in the number of erosions and ulcers were observed between the buffered and enteric-coated aspirin groups (P=0.017 and P=0.037, respectively). The median Lewis score for the small bowel mucosal inflammatory change was significantly higher in the enteric-coated aspirin group than in the buffered aspirin group (P=0.035). ConclusionsThe results of this study suggested that enteric-coated aspirin might be more injurious to the small bowel mucosa than buffered aspirin.

Tu1066 Efficacy of Probiotic Treatment on Small Bowel Injury in Chronic Low-Dose Aspirin Users: A Pilot Randomized Controlled Trial

Tu1066 Efficacy of Probiotic Treatment on Small Bowel Injury in Chronic Low-Dose Aspirin Users: A Pilot Randomized Controlled Trial

Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study

Few studies have investigated measures to prevent small bowel injuries induced by aspirin. Our aim was to evaluate the effect of probiotic treatment on the small bowel injuries induced by chronic low-dose aspirin use. Thirty-five patients who took low-dose enteric-coated aspirin 100mg daily (for more than 3months) plus omeprazole 20mg daily and were diagnosed as having unexplained iron deficiency anemia participated in this prospective randomized controlled trial. We assigned the patients to receive probiotic treatment with Lactobacillus casei for 3months (L. casei group) or not receive the probiotic (control group). Patients underwent capsule endoscopy (CE) before and after treatment. Twenty-five patients, including 13 in the L. casei group and 12 in the control group, underwent the full analysis. Significant decreases in the number of mucosal breaks and the CE score were observed at the 3-month evaluation in the L. casei group as compared with the results in the control group (P=0.039). The change from the baseline in the median number of mucosal breaks in the L. casei group was -2, as compared with 0.5 in the control group. The change from the baseline in the median CE score in the L. casei group was -228 compared with -4 in the control group (P=0.026). Co-administration of L. casei is effective for the treatment of aspirin-associated small bowel injury.

Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy

The antithrombotic effects of low-dose aspirin (LDA) are well established, and it is used for primary and secondary prevention of cardiovascular events. However, the small intestinal toxicity of LDA remains unclear. The aim of this study was to review the characteristics of small bowel injury in long-term LDA users with capsule endoscopy (CE). We retrospectively reviewed all chronic LDA users (>3 months) who underwent CE for suspected small bowel diseases from May 2004 to May 2008 at two medical centers. At our institutions, a total of 22 patients (13 males and 9 females, mean age 66.3 years) taking LDA underwent a CE examination. The indications for CE were obscure gastrointestinal bleeding in 21 patients and 1 patient who had abdominal pain. Twenty-one patients (95.5%) had some small bowel mucosal injury. Small bowel erosions were identified in 14 patients (63.6%). This enteropathy was characterized by multiple petechiae, loss of villi, erosions, and ulcers with round, irregular, and punched-out shapes. Two patients had circumferential ulcers with stricture. In most patients, small bowel lesions were multifocal and were evenly distributed in the small bowel. No patients failed to pass the capsule. This is the first CE report that has studied the characteristics of small bowel injury in chronic LDA users. CE is useful to diagnose small bowel enteropathy associated with LDA.

Does Adding Misoprostol to Standard Intravenous Proton Pump Inhibitor Protocol Improve the Outcome of Aspirin/NSAID-Induced Upper Gastrointestinal Bleeding?

Aspirin and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal bleeding is recognized as an important health problem. We performed a single-center randomized clinical trial to compare the effect of high-dose intravenous proton pump inhibitor (omeprazole) alone (group 1) with omeprazole in combination with a low-dose prostaglandin analog (misoprostol; group 2) on clinical outcomes in patients with aspirin/NSAID-induced upper gastrointestinal bleeding. Additionally, we evaluated the contribution of Helicobacter pylori eradication therapy on the late consequences. Patients were recruited to the study if they had upper gastrointestinal bleeding with history of taking aspirin or other NSAIDs within the week before the onset of bleeding. All were evaluated in terms of probable risk factors. After the standard treatment protocol, patients with histologically proven H pylori infection were prescribed a triple eradication therapy for 14 days. The primary end points were recurrent bleeding, surgery requirement, and death rates before discharge and at the end of follow-up period. This study lasted for 2 years. A total of 249 patients with upper gastrointestinal bleeding were admitted, and 49.7% of these patients were users of aspirin/NSAIDs. There were 67 patients in group 1 and 56 in group 2. The distributions for gender, age, comorbidity, H pylori infection, and high-risk ulcer rate were similar in both groups. Among aspirin/NSAID users, endoscopy revealed duodenal ulcer in 47 (38.2%), gastric ulcer in 10 (8.1%), and erosive gastropathy in 33 (26.8%). The overall rebleeding occurred in 12.2%, death in 2.4% of the patients. The in-hospital death (P=.414), rebleeding (P=.925), and surgery (P=.547) rates were similar in both treatment groups. After the follow-up period of 3 months, overall rebleeding occurred in 4.1%, and death in 4.8% of the patients. The overall mortality rate was highest in those >65 years old, who were chronic low-dose aspirin users with comorbidity. One died of transfusion-related graft-versus-host disease. In this pilot study, we indicated that adding misoprostol (600 microg/day) to standardized proton pump inhibitor treatment did not improve or change the rebleeding or mortality rates of patients with upper gastrointestinal bleeding related to aspirin/NSAID use. Other prospective studies on higher doses of misoprostol are needed to establish the coeffect. One should bear in mind that all blood products must be irradiated before transfused to the host.