Low-dose Enteric-coated Aspirin Research Articles

Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study.

This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14days, with a washout period of 28days, followed by Vazalore® LD PL-ASA daily for 14days, again followed by ARU testing. Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024.

Low-Dose Enteric-Coated and Chewable Aspirin Are Not Equally Effective in Preventing Venous Thromboembolism in Total Knee and Hip Arthroplasty

BackgroundLow-dose aspirin is an effective venous thromboembolism (VTE) prophylactic medication in primary total joint arthroplasty, but the efficacy and safety of the formulations of chewable and enteric-coated aspirin have not been compared. The purpose of this study was to investigate the VTE and gastrointestinal (GI) complication rates of chewable and enteric-coated 81 mg aspirin bis in die for VTE prophylaxis in primary total joint arthroplasty. MethodsA retrospective, single-institution cohort study was performed on patients who underwent primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2017 to 2021. Comparisons were made between 4,844 patients who received chewable, noncoated aspirin 81 mg and 4,388 patients who received enteric-coated 81 mg aspirin. Power analysis demonstrated 1,978 and 3,686 patients were needed per group to achieve a power of 80% for 90-day VTE rates (using inferiority testing) and GI complications (using superiority testing), respectively. Patients had similar baseline characteristics. Statistical analyses were done using t-tests and Chi-squared tests, with statistical significance defined as a P value < .05. ResultsThere were no significant differences in the incidences of postoperative VTE (0.31% versus 0.55%; P = .111) or GI complications (0.14% versus 0.14%; P = 1.000) between patients who received either chewable or enteric-coated 81 mg aspirin bis in die in the overall comparison that included both THA and TKA patients combined, or THA patients alone. However, the VTE incidence for TKA patients alone was significantly lower with chewable than enteric-coated aspirin (0.22% versus 0.62%; P = .037), with no difference in GI complications (0.13% versus 0.19%; P = .277). ConclusionsLow-dose aspirin in enteric-coated formulation is inferior to chewable aspirin for VTE prophylaxis in primary TKA, but not inferior in THA patients. Both formulations have a similar GI complication rate. Therefore, it is reasonable to consider a transition from enteric-coated to uncoated chewable low-dose aspirin.

Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients.

The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas. In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2). However, enhanced residual urinary 11-dehydro-TXB2 and urinary PGEM, primary metabolites of TXA2 and prostaglandin (PG)E2, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB2 levels, possibly identifying the nonresponders and responders to Aspirin. Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA2 and PGE2 biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA2 and PGE2 signaling with receptor antagonists.

Small Intestinal Perforation Caused by Enteric-coated Low-dose Aspirin: A Case Report.

A 77-year-old man presented with abdominal pain for 1 week. He was taking enteric-coated low-dose aspirin (LDA) to prevent secondary cardiovascular events and a proton pump inhibitor (PPI). Computed tomography indicated a small intestinal perforation; thus, small intestine resection was performed. Two months after surgery, he experienced a recurrence of the perforation. Since his repeated perforation was suspected to be due to LDA, LDA was discontinued. He has experienced no further recurrence since then. This is the first case of small intestinal perforation caused by enteric-coated LDA. Enteric-coated LDA may cause small intestinal perforation in patients with severe atherosclerosis under PPI administration.

Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective, randomized, crossover study

Low dose enteric-coated aspirin (EC-ASA) is routinely used for secondary cardiovascular event prevention. However, absorption of EC tablets is poor, which can result in subtherapeutic antiplatelet effects. Phospholipid-aspirin liquid filled capsules (PL-ASA) are a novel FDA-approved immediate-release formulation designed to reduce gastrointestinal (GI) injury by limiting direct contact with the stomach lining. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of PL-ASA versus EC-ASA at a low dose. This randomized, open-label, crossover study assessed PK and PD following a single 81-mg dose of PL-ASA versus EC-ASA under fasting conditions in 36 volunteers without cardiovascular disease between 18 and 75 years of age. Volunteers were randomly assigned 1:1 to either PL-ASA then EC-ASA or vice versa with a minimum 14-day washout. Assessments included PK parameters for acetylsalicylic acid and salicylic acid, platelet aggregation in response to arachidonic acid (AA), and serum thromboxane B2 (TxB2) assessments over 24 h. PL-ASA was rapidly absorbed. PL-ASA reached Tmax 3 h earlier (1.01 vs. 4.00 h, p < 0.0001), with almost double the Cmax (720 vs. 368 ng/mL, p < 0.0001) and overall 44% higher exposure of acetylsalicylic acid (AUC0-t: 601 vs. 416 h*ng/mL, p = 0.0013) compared with EC-ASA. Within 1 h of dosing, PL-ASA achieved significantly lower residual platelet aggregation, which persisted for the full 24 h (median AA-LTA was 47% with PL-ASA vs. 80.5% with EC-ASA; p = 0.0022 at hour-24). Treatment with PL-ASA also resulted in significantly lower serum TxB2 concentrations at each time point compared with EC-ASA (all p-values < 0.05). PL-ASA resulted in faster and more complete aspirin absorption paralleled by more prompt and potent platelet inhibition compared with EC-ASA after a single 81 mg dose. PL-ASA represents an attractive novel aspirin formulation for the secondary prevention of cardiovascular events.Clinical Trial Registration ClinicalTrials.gov identifier: NCT04811625.

Relationship between Adverse Gastric Reactions and the Timing of Enteric-Coated Aspirin Administration.

This study aimed to elucidate the association between the adverse gastric effects of enteric-coated aspirin and the timing of its administration. The study population comprised 572 patients (age range 45-84 years) admitted to Huaiyin Hospital between August 2012 and October 2014. Patients were administered a 100mg enteric-coated aspirin tablet once daily: before a meal (30min before a meal), during a meal, after a meal (30min after a meal), or before sleep, and all patients were followed up for 6-9 months to observe for adverse gastric reactions and other side effects. Gastroscopy was performed if indicated by the patient's condition after obtaining due consent. In addition, release tests for an enteric-coated aspirin tablet were conducted using the chromatography method. Enteric-coated aspirin tablets released completely, with a release rate of >99% under 20-120min at pH >5.5. Furthermore, the number of patients with recurring adverse stomach reactions was significantly lower in the before-meal and before-sleep groups than that observed in the during-meal and after-meal groups (p<0.05). No significant between-group differences were observed with respect to damage to other organs. Similarly, the number of patients with gastric lesions was significantly lower in the before-meal and before-sleep groups than that observed in the during-meal and after-meal groups (p<0.05). The optimal time for once-daily administration of low-dose enteric-coated aspirin tablets was before a meal or before sleep owing to the increase in pH level during and after meals.

Reappraisal of the clinical pharmacology of low‐dose aspirin by comparing novel direct and traditional indirect biomarkers of drug action

Even though the acetylation of platelet cyclooxygenase (COX)-1 at serine-529 is the direct mechanism of action of low-dose aspirin, its antiplatelet effect has been characterized using indirect indexes of COX-1 activity. We performed a clinical study with enteric-coated low-dose aspirin (EC-aspirin), in healthy subjects, to evaluate the effects on the extent and duration of platelet COX-1 acetylation, using a novel proteomic strategy for absolute protein quantification (termed AQUA), as compared with traditional pharmacokinetic and pharmacodynamic parameters. In a phase I, single-arm, open-label study of EC aspirin (100 mg day(-1) ) administered to 24 healthy subjects, we compared, over a 24 h-period on day 1 and 7, % platelet acetylated COX-1 (AceCOX-1) with traditional pharmacokinetic and pharmacodynamics [i.e. serum thromboxane (TX) B2 , platelet function by monitoring CEPI(collagen/epinephrine) closure time (CT) using whole-blood PFA-100 and urinary excretion of 11-dehydro-TXB2 ] parameters. Acetylation of platelet COX-1 was measurable before detection of aspirin levels in the systemic circulation and increased in a cumulative fashion upon repeated dosing. After the last dose of EC-aspirin, %AceCOX-1, serum TXB2 and CEPI-CT values were maximally and persistently modified throughout 24 h; they averaged 76 ± 2%, 99.0 ± 0.4% and 271 ± 5 s, respectively. EC-aspirin caused 75% reduction in urinary 11-dehydro-TXB2 excretion. After chronic dosing with aspirin, the pharmacokinetics of acetylsalicylic acid was completely dissociated from pharmacodynamics. The demonstrated feasibility of quantifying the extent and duration of platelet COX-1 acetylation will allow characterizing the genetic, pharmacokinetic and pharmacodynamic determinants of the inter-individual variability in the antiplatelet response to low-dose aspirin as well as identifying extra-platelet sites of drug action.

Difference in risk of gastrointestinal complications between users of enteric-coated and buffered low-dose aspirin

Difference in the risk of gastrointestinal (GI) complications between users of enteric-coated and buffered low-dose aspirin (LDA) is unclear. The purpose of the study is to examine the difference in risk of GI damage between enteric-coated and buffered LDA products. A large and chronologically organized receipt database constructed by a database vendor was utilized. Prescription and event sequence symmetry analysis was used to identify the risk of LDA-induced GI complications over the period from January 2005 to July 2011. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was examined by prescription sequence symmetry analysis. Likewise, symmetry analysis was undertaken to evaluate the association between the diagnosis of GI disease and the prescription of LDA products. In July 2011, enteric-coated LDA users were more frequently co-administered PPIs than buffered LDA users (25.4% vs. 14.4%). Prescription sequence symmetry analysis of acid inhibitor use found no significant associations with enteric-coated LDA use and buffered LDA use. The event sequence symmetry analysis of ulcer, gastritis and duodenitis, and melena found significant associations with entericcoated LDA use, with adjusted sequence ratios (ASRs) of 1.58 (1.23 - 2.06), 1.30 (1.03 - 1.65), and 14.38 (2.19 - 607.95), respectively, at the 6-month interval. At the 12-month interval, analysis of ulcers and melena found significant associations for enteric-coated LDA users, with ASRs of 1.39 (1.13 - 1.73) and 20.83 (3.33 - 863.25), respectively. Our findings do not support that there is no difference in the risk of GI complications between enteric-coated LDA and buffered LDA, but rather may imply that the risk of GI complications associated with enteric-coated LDA is higher than that with buffered LDA.

The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial

ObjectiveTo evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy.DesignA double-blinded, randomised,...

Difference between the frequencies of antisecretory drug prescriptions in users of buffered vs. enteric-coated low-dose aspirin therapies

To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 - 3.03) and 1.87 (95% CI, 1.26 - 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). Our findings do not support the notion that entericcoated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA.

Relationship between continuous use of low-dose enteric-coated aspirin and gastrointestinal injuries in patients with gastrointestinal hemorrhage

Gastrointestinal disorders are important side effects of aspirin therapy, even if the low-dose enteric-coated form is administered. The aim of the current study was to present the upper and lower endoscopic features of patients with gastrointestinal hemorrhage using low-dose enteric-coated aspirin. This prospective study was conducted among 633 consecutive patients with gastrointestinal hemorrhage who admitted to our tertiary referral hospital for endoscopy assessment. Patients were divided into two groups as low-dose aspirin users (n=168) and non-aspirin users (n=495). Aspirin users included those who were taking 80-100 mg of enteric-coated aspirin per day. Ulcer lesions were found in 78 patients in the aspirin user group and in 113 patients in the control group. Prevalence of duodenal ulcer was statistically similar between the two groups; however, gastric ulcer was seen more in the aspirin-user group. The use of low-dose aspirin could strongly predict gastric ulcers in the patients examined by endoscopy (p<0.001). Overall prevalence of peptic ulcer disease in those with confirmed Helicobacter pylori infection was significantly higher than in non-infected ones (p<0.001). The presence of this infection was strongly associated with peptic ulcer disease in the aspirin-user group (p<0.001). Multivariable analysis also demonstrated that the use of aspirin had a main triggering effect on short-term mortality following gastrointestinal endoscopy (p=0.003). Low-dose enteric-coated aspirin causes significant gastric endoscopic lesions and even predicts mortality due to progression of gastrointestinal disorders.

Low-dose enteric-coated aspirin does not inhibit thromboxane B2 and prostaglandin E2: data-derived hypothesis formulation

Background: All usual daily doses of plain aspirin inhibit thromboxane B2 (TXB2) as well as prostaglandin E2 (PGE2). The role of 81-mg enteric-coated aspirin (ECA) is controversial. Method: In a randomized, double-blind trial, 37 patients (25 men and 12 women) with chronic stable coronary disease taking ECA 81 mg at baseline were assigned to plain aspirin 81, 162.5, 325, 650 or 1300 mg daily for 12 weeks. At baseline and 12 weeks, blood was tested for TXB2 and PGE2. Results: All doses of plain aspirin produced virtually identical reductions in TXB2 and PGE2. For all doses combined, the mean ratio of the 12-week to baseline value was 0.03 for TXB2 (p < 0.001) and 0.63 for PGE2 (p < 0.001). Conclusion: These data indicate that ECA 81 mg daily does not inhibit TXB2 and PGE2, markers of acute and systemic responses to aspirin. Randomized trials designed a priori to test this hypothesis are necessary.

Impact of a Fixed-Dose Combination of Naproxen and Esomeprazole Magnesium on Serum Thromboxane B 2 Inhibition by Low-Dose Aspirin Over 5 Days in Healthy Adults: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Noninferiority Trial

Background Low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are often used concomitantly; however, some NSAIDs may interfere with LDA antiplatelet activity. Objective We evaluated the impact of coadministered enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg (fixed-dose combination) on LDA-mediated platelet cyclooxygenase (COX)-1 inhibition. Methods In this Phase I, single-center, double-blind, placebo-controlled study, healthy volunteers (50–75 years) received enteric-coated LDA 81 mg once daily (QD) on days 1 to 5 (open-label), then enteric-coated LDA 81 mg QD plus either naproxen/esomeprazole magnesium or placebo twice daily (BID) on days 6 to 10 (randomized). Serum thromboxane B 2 (TXB 2) inhibition from baseline to day 11 was the primary end point. The primary analysis excluded volunteers with ≤95% inhibition at day 6. Assay sensitivity and noninferiority of naproxen/esomeprazole magnesium versus placebo were concluded if the 90% CI lower limit for percent inhibition of TXB 2 was >90.0% in both treatment groups (prespecified criterion). Tolerability was a secondary end point. Results Overall, 42 volunteers were enrolled, 40 randomized, and 32 included in the primary pharmacodynamic analysis (day 6 TXB 2 inhibition ≥95%). Most volunteers (86%) were white, and 57% were female. Mean age was 60 (7) years, and mean body mass index was 26.4 (2.6) kg/m 2. Day 11 mean serum TXB 2 inhibition was 99.1% (90% CI, 98.7–99.6) in the LDA plus placebo group (n = 18) versus 99.6% (90% CI, 99.4–99.8) in the LDA plus naproxen/esomeprazole magnesium group (n = 14). Noninferiority of naproxen/esomeprazole magnesium versus placebo was established (CI lower limit >90.0%). Adverse event (AE) incidence was 40% (n = 8/20) in the LDA plus placebo group and 15% (n = 3/20) in the LDA plus naproxen/esomeprazole magnesium group. No serious AEs or discontinuations due to AEs were observed. Conclusions This pilot investigation suggests that LDA coadministered with naproxen/esomeprazole magnesium is noninferior to LDA alone for platelet COX-1 inhibition, as measured by serum TXB 2 concentration, in healthy volunteers. ClinicalTrials.gov identifier: NCT01094483

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.

Effect of maximum OTC doses of naproxen sodium or acetaminophen on low-dose aspirin inhibition of serum thromboxane B2

Objectives:This study evaluated the platelet inhibitory effects of low-dose enteric-coated aspirin (EC-ASA) when used concomitantly with maximum over-the-counter (OTC) doses of naproxen sodium (NAPSO) or acetaminophen to determine whether NAPSO and acetaminophen interfere with the anti-platelet effect of aspirin.Research design and methods:Phase I, randomized, open-label, multi-dose, three-period, parallel group, pharmacodynamic trial conducted in healthy male and female volunteers (n = 47 randomized subjects and n = 37 evaluable subjects), mean age 40.2 years. All subjects received 5 days of EC-ASA 81 mg once daily followed by 5 days of EC-ASA 81 mg once daily alone or co-administered with either NAPSO 220 mg three times daily or acetaminophen 1 g four times daily.Primary outcome measure:Inhibition of serum thromboxane B2 (TXB2), as a marker of platelet cyclooxygenase-1 (COX-1) inhibition, measured on Day 11.Results:Mean inhibition of TXB2 on Day 11 was >99% for subjects taking EC-ASA alone as well as for those who received EC-ASA co-administered with NAPSO or acetaminophen. For subjects taking EC-ASA monotherapy, mean serum TXB2 inhibition was 99.7% (range 99.0–100%), for those taking EC-ASA with acetaminophen it was 99.6% (range 98.3–99.9%), and for those taking EC-ASA with NAPSO, mean serum TXB2 inhibition was 99.7% (range 99.2–100%).Study limitation:Small sample size and open-label trial design.Conclusions:The anti-platelet effect of EC-ASA 81 mg once daily was maintained following its co-administration with maximum OTC doses of NAPSO or acetaminophen.

Randomized, double-blind, pilot study of geranylgeranylacetone versus placebo in patients taking low-dose enteric-coated aspirin. Low-dose aspirin-induced small bowel damage

Objective. Low-dose enteric-coated aspirin is increasingly being used for prevention of cardiovascular disease. The aim of this study was to evaluate whether geranylgeranylacetone (GGA) could prevent aspirin-induced small bowel injury. Material and methods. This was a prospective, randomized, double-blind, pilot study of GGA versus placebo in subjects taking low-dose enteric-coated aspirin. Young healthy volunteers were enrolled and each received 100 mg of enteric-coated aspirin per day plus either GGA (150 mg/day) or matching placebo for 7 days. Video capsule endoscopy of the small bowel and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire were performed before and after the administration of aspirin. Results. Twenty volunteers were evaluated. There was no significant difference in the number of lesions in any category between those receiving or not receiving GGA. Large erosions or ulcers were observed in 12 (60%; 95% confidence interval 36%– 80%) aspirin users. Mucosal breaks were most frequently found in the latter half of the proximal small bowel. Conclusions. Short-term administration of low-dose enteric-coated aspirin was associated with visible small bowel damage in the majority of users. We could not prove that aspirin-induced small bowel mucosal injury was prevented by GGA.

Platelet inhibitory effects of OTC doses of naproxen sodium compared with prescription dose naproxen sodium and low-dose aspirin

Objectives: Prescription dose naproxen has been reported to have an antiplatelet effect similar to low-dose aspirin (ASA). This study evaluated the platelet inhibitory effects of over-the-counter (OTC) doses of naproxen sodium (NAPSO) compared to that of a prescription dose of NAPSO and to low-dose enteric-coated aspirin (EC-ASA).Research design and methods: This was a phase I, open-label, randomized, placebo-controlled, two-way crossover, multi-dose, pharmacodynamic trial conducted in healthy male and female volunteers (n = 48, mean age = 41.7 years). All subjects received 7 days of either prescription dose NAPSO (550 mg twice daily), OTC doses of NAPSO (220 mg two or three times daily), or placebo twice daily (period 1). After a minimum 6-day washout period, all subjects then received 7 days of EC-ASA 81 mg once daily (period 2). All study medications were taken by mouth.Primary outcome measure: Inhibition of serum thromboxane B2 (TXB2), as a marker of platelet cyclooxygenase-1 (COX-1) inhibition, measured 24 h after the day 7 morning dose. This was measured after both period 1 and period 2.Results: After 7 days of treatment in period 1, mean inhibition of TXB2 was 47% for placebo and ≥98% for all doses of NAPSO. After 7 days of EC-ASA 81 mg, mean inhibition of TXB2 was ≥ 97% (period 2).Study limitations: Out-patient study setting.Conclusions: These data suggest that OTC doses of NAPSO (220 mg two or three times daily) have an antiplatelet effect similar to EC-ASA 81 mg and to prescription dose NAPSO (550 mg twice daily).

Do Proton Pump Inhibitors Attenuate the Effect of Aspirin on Platelet Aggregation? A Randomized Crossover Study

It is common practice to coadminister proton pump inhibitors with aspirin to diminish the risk of upper gastrointestinal bleeding. This is the first study that investigated the potential impact of a proton pump inhibitor on aspirin effects on platelet aggregation. Twenty-four hypertensive subjects eligible for treatment with low-dose enteric-coated aspirin (LDECA) for primary prevention of cardiovascular disease were randomized to receive 100 mg LDECA or 100 mg LDECA plus 30 mg lansoprazole for 4 weeks. Then, participants were crossed over to the alternative regimen for another 4 weeks. Salicylic, gastrin, and pepsinogen I blood level counting were used to ensure adherence to treatment. Platelet aggregation was evaluated by light transmittance aggregometry and PFA100. The LDECA administration reduced arachidonic acid (P < 0.001), collagen (P < 0.01), and epinephrine (P < 0.001) tests. These changes paralleled an increase in collagen/epinephrine duration (P < 0.001) but not in collagen/adenosine diphosphate duration and platelet count. No significant difference was found in any of these platelets' function tests with LDECA alone versus LDECA plus lansoprazole. A significant increase in salicylic levels was observed in patients on LDECA as well as in those on LDECA plus lansoprazole, whereas gastrin and pepsinogen I levels were increased only when lansoprazole was added. These data suggest that the concomitant use of the lansoprazole at 30-mg daily does not influence the long-term effect of LDECA on platelet aggregation. Furthermore, they might imply that an interaction of LDECA with other proton pump inhibitors on platelet aggregation is unlikely.

Small Bowel Injury by Low-Dose Enteric-Coated Aspirin and Treatment With Misoprostol: A Pilot Study

With capsule endoscopy, the ulcerogenic effect of low-dose enteric-coated aspirin on the small bowel and the therapeutic effect of misoprostol on intestinal injury were evaluated. Eleven patients who developed gastric ulcers while undergoing low-dose enteric-coated aspirin therapy were enrolled. They continued aspirin therapy while taking proton pump inhibitors (PPIs) for 8 weeks to heal the gastric ulcers. Then misoprostol 200 microg 4 times a day was administered instead of PPIs for 8 weeks. When the patients could not tolerate misoprostol as a result of side effects, they received another 8 weeks of PPI therapy. Capsule endoscopy performed after 8 weeks of PPI treatment identified red spots and mucosal breaks in 100% (11/11) and 90.9% (10/11) of patients, respectively. In 7 patients who completed the study protocol, misoprostol significantly decreased the median number of red spots and mucosal breaks, with complete disappearance of mucosal breaks in 4 patients. Intestinal lesions tended not to heal in 3 patients who discontinued misoprostol. Low-dose enteric-coated aspirin frequently damages the small intestine, and misoprostol is effective in the treatment of aspirin-induced enteropathy.

T1318 Incidence of Small Bowel Injury By Low-Dose Enteric-Coated Aspirin, and Efficacy of Misoprostol in Treating It - A Pilot Study with Capsule Endoscopy

T1318 Incidence of Small Bowel Injury By Low-Dose Enteric-Coated Aspirin, and Efficacy of Misoprostol in Treating It - A Pilot Study with Capsule Endoscopy