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  1. Veettil SK, Kew ST, Lim KG, Phisalprapa P, Kumar S, Lee YY, et al.
    BMC Gastroenterol, 2021 Mar 20;21(1):130.
    PMID: 33743605 DOI: 10.1186/s12876-021-01715-7
    BACKGROUND: Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC).

    METHODS: Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk-benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained.

    RESULTS: According to NMA, the risk-benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective.

    CONCLUSION: ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.

    Matched MeSH terms: Aspirin/adverse effects
  2. See IO
    Med J Malaysia, 1996 Mar;51(1):159-60.
    PMID: 10968003
    Matched MeSH terms: Aspirin/adverse effects*
  3. Tan BE, Wong PY, Baibhav B, Thakkar S, Azhar AZ, Rao M, et al.
    Curr Probl Cardiol, 2023 Aug;48(8):101174.
    PMID: 35341798 DOI: 10.1016/j.cpcardiol.2022.101174
    Current guidelines recommend 6-12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) followed by aspirin monotherapy indefinitely. We aimed to assess the efficacy and safety of clopidogrel vs aspirin in the post-PCI population after completing DAPT. We systematically searched 5 electronic databases to identify studies comparing clopidogrel with aspirin following completion of DAPT after PCI. We pooled outcomes for major adverse cardiac events (MACE), cardiac death, all-cause death, major bleeding, myocardial infarction (MI), and stroke. We included 5 studies with 13,850 patients, of whom 5601 (40.4%) received clopidogrel. Mean follow-up was 12-36 months. All patients received drug-eluting stents. Duration of DAPT before antiplatelet monotherapy was 1-18 months. Clopidogrel was associated with reductions in MACE (Risk ratio [RR] 0.77, 95% confidence interval [CI] 0.65-0.91), any stroke (RR 0.51; 95% confidence interval [CI] 0.35-0.76), ischemic stroke (RR 0.55; 95% CI 0.32-0.94), and hemorrhagic stroke (RR 0.24; 95% CI 0.09-0.68) when compared with aspirin. Cardiac death (RR 0.87; 95% CI 0.53-1.41), all-cause death (RR 1.06; 95% CI 0.81-1.39), major bleeding (RR 0.74; 95% CI 0.43-1.29), MI (RR 1.01; 95% CI 0.64-1.60), repeat revascularization (RR 0.88; 95% CI 0.71-1.09), target vessel revascularization (RR 0.76; 95% CI 0.52-1.13), and stent thrombosis (RR 0.96; 95% CI 0.35-2.59) were not significantly different among groups. Compared with aspirin, clopidogrel was associated with reductions in MACE and stroke (ischemic and hemorrhagic) following DAPT completion after PCI. There were no significant differences in mortality, major bleeding, MI, and repeat revascularization between groups.
    Matched MeSH terms: Aspirin/adverse effects
  4. Goh KL, Chan WK
    Aliment Pharmacol Ther, 2012 Aug;36(3):291-2; discussion 292-3.
    PMID: 22747451 DOI: 10.1111/j.1365-2036.2012.05164.x
    Matched MeSH terms: Aspirin/adverse effects*
  5. Ng SC, Lee MK, Teh A
    Postgrad Med J, 1989 Nov;65(769):843-4.
    PMID: 2616421
    A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome.
    Matched MeSH terms: Aspirin/adverse effects
  6. Cugadasan V
    Med J Malaysia, 1980 Sep;35(1):73-6.
    PMID: 7254004
    Matched MeSH terms: Aspirin/adverse effects
  7. Veettil SK, Lim KG, Ching SM, Saokaew S, Phisalprapa P, Chaiyakunapruk N
    BMC Cancer, 2017 Nov 14;17(1):763.
    PMID: 29137605 DOI: 10.1186/s12885-017-3757-8
    BACKGROUND: Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established.

    METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).

    RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.

    CONCLUSION: Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

    Matched MeSH terms: Aspirin/adverse effects*
  8. Sha'aban A, Zainal H, Khalil NA, Abd Aziz F, Ch'ng ES, Teh CH, et al.
    Molecules, 2022 Mar 25;27(7).
    PMID: 35408523 DOI: 10.3390/molecules27072126
    BACKGROUND: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, although limited by gastric toxicity. This study aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics.

    METHODS: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats' stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity.

    RESULTS: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R2Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q2Y) of -0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R2Y value of 0.726 and Q2Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity.

    CONCLUSION: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.

    Matched MeSH terms: Aspirin/adverse effects
  9. Ali Khan MS, Mat Jais AM, Afreen A
    Biomed Res Int, 2013;2013:185476.
    PMID: 24350249 DOI: 10.1155/2013/185476
    The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous.
    Matched MeSH terms: Aspirin/adverse effects
  10. Jalil NJ, Bannur Z, Derahman A, Maskon O, Darinah N, Hamidi H, et al.
    J Pharm Pharm Sci, 2015;18(3):474-83.
    PMID: 26517138
    PURPOSE:   Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated.

    METHODS: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR).

    RESULTS: Variants UGT1A6*2,*3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value < 0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033).

    CONCLUSION: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

    Matched MeSH terms: Aspirin/adverse effects
  11. Jaarin K, Gapor MT, Nafeeza MI, Fauzee AM
    Int J Exp Pathol, 2002 Dec;83(6):295-302.
    PMID: 12657138 DOI: 10.1046/j.1365-2613.2002.00242.x
    This study examined the effects of vitamin E on the prevention of aspirin-induced gastric lesions. The study was divided into two phases. Phase 1 determined the effects of various doses of palm vitamin E on the factors affecting mucosal integrity. Thirty-two male rats of the Sprague-Dawley strain (200-250 g) were randomly divided into four groups. Group I was fed a normal diet (control), Groups II, III and IV were fed a diet supplemented with palm vitamin E in a dose of 60 mg/kg food, 100 mg/kg food and 150 mg/kg food, respectively. The rats were killed after 4 weeks of feeding for the determination of gastric malondialdehyde (MDA), acid and mucus content. There was a significant decrease in gastric MDA and gastric acid in all the palm vitamin E supplemented groups compared to control. However, these doses of palm vitamin E had no significant effect on gastric mucus. The phase 2 study determined the effect of multiple doses of palm vitamin E and tocopherol on the prevention of aspirin-induced gastric lesions. Fifty rats of the same weight and strain were randomized into seven groups. Group I was fed a normal diet; groups II to IV were fed with a palm vitamin E enriched diet in doses of 60 mg, 100 mg and 150 mg/kg food, respectively; groups V to VII were fed with a tocopherol-enriched diet in doses of 20 mg, 30 mg and 50 mg/kg food, respectively. After 4 weeks of feeding with the respective diets the rats were challenged with a single intra-gastric dose of 400 mg/kg body weight aspirin suspended in propylene glycol. The rats were killed 6 h post-aspirin exposure for the determination of gastric lesion index and gastric parameters as mentioned in the phase I study. The gastric lesions index was significantly lower in all the vitamin E groups compared to control. The lowest ulcer index was observed in the groups that received 100 mg of palm vitamin E and 30 mg tocopherol in the diet. However, there was no significant difference in ulcer indices between palm vitamin E and tocopherol-treated groups. The lower ulcer index was only accompanied by lower gastric MDA content. We conclude that both palm vitamin E in doses of 60 mg, 100 mg and 150 mg/kg food as well as tocopherol in doses of 20 mg, 30 mg and 50 mg/kg food are equally effective in preventing aspirin-induced gastric lesions. The most probable mechanism is through their ability in limiting the lipid peroxidation that is involved in aspirin-induced gastric lesions.
    Matched MeSH terms: Aspirin/adverse effects*
  12. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al.
    Gastroenterology, 2019 08;157(2):403-412.e5.
    PMID: 31054846 DOI: 10.1053/j.gastro.2019.04.041
    BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.

    METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.

    RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).

    CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

    Matched MeSH terms: Aspirin/adverse effects
  13. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al.
    Gastroenterology, 2019 09;157(3):682-691.e2.
    PMID: 31152740 DOI: 10.1053/j.gastro.2019.05.056
    BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.

    METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.

    RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.

    CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

    Matched MeSH terms: Aspirin/adverse effects
  14. Sessler DI, Conen D, Leslie K, Yusuf S, Popova E, Graham M, et al.
    Anesthesiology, 2020 04;132(4):692-701.
    PMID: 32022771 DOI: 10.1097/ALN.0000000000003158
    BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.

    METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.

    RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).

    CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

    Matched MeSH terms: Aspirin/adverse effects
  15. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al.
    N Engl J Med, 2017 10 05;377(14):1319-1330.
    PMID: 28844192 DOI: 10.1056/NEJMoa1709118
    BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.

    METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.

    RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.

    CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

    Matched MeSH terms: Aspirin/adverse effects
  16. Zou D, Goh KL
    J Gastroenterol Hepatol, 2017 Jun;32(6):1152-1159.
    PMID: 28024166 DOI: 10.1111/jgh.13712
    Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.
    Matched MeSH terms: Aspirin/adverse effects
  17. Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, et al.
    Lancet, 2018 01 20;391(10117):205-218.
    PMID: 29132879 DOI: 10.1016/S0140-6736(17)32458-3
    BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.

    METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.

    FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012).

    INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.

    FUNDING: Bayer AG.
    Matched MeSH terms: Aspirin/adverse effects
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