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Background: Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users., Objective: The objective of this study was to investigate the occurrence of upper GI symptoms, and their impact on well-being, among patients taking low-dose ASA for CV risk management., Study Design: This was a multicenter, non-interventional, 12-week study carried out in primary-care, cardiology, and practice group centers in the USA, Canada, and France., Patients: Eligible patients were adults (age ≥18 years) at risk of or with confirmed CV disease, with physician-prescribed/-recommended low-dose ASA (75-325 mg) use., Main Outcome Measures: An electronic device (eDiary) was used to collect patient-reported outcome data three times per day (morning, afternoon, and evening; regular reports), including upper GI (gastroesophageal disease [GERD]-like or dyspepsia-like) symptoms and the impact of such symptoms on sleep quality, perceived stress, and emotions. In addition to regular reports, patients were able to self-initiate a report of upper GI symptoms (spontaneous reports)., Results: Overall, 81,282 eDiary reports (including 4,407 spontaneous reports of upper GI symptoms) were collected from 340 patients. Upper GI symptoms (most commonly GERD-like) were commonly blamed on food/drink (39 %), and around one-third of patients (37 %) used medication to relieve their symptoms. Analysis showed that upper GI symptoms had a negative impact on sleep quality, perceived stress, and emotions (all p < 0.01). Overall, GI medication use was infrequent, but was more common among low-dose ASA-experienced patients (41 % vs. 12 % of evening reports in patients naïve to low-dose ASA at baseline; p < 0.01); adherence to prescribed daily proton pump inhibitors (PPIs) was poor (47 %)., Conclusion: Upper GI symptoms impact negatively on well-being among low-dose ASA users, in terms of decreased quality of sleep, increases in perceived stress, and negative impact on emotions. Despite this, patients may not necessarily associate these symptoms with their low-dose ASA therapy and do not readily take steps to manage such symptoms, which extends to poor adherence to prescribed daily PPIs.

Objective: The aim of this study was to investigate the bioequivalence of a single oral dose of esomeprazole 40 mg and acetylsalicylic acid 325 mg when formulated as a single capsule, relative to the components given as separate monotherapies., Methods: This was an open, randomized, single-center, single-dose, 2-stage group sequential design, 2-way crossover study (NCT00688428) in 49 healthy adult volunteers (29 women). In each treatment period, subjects received a single dose of esomeprazole 40 mg and ASA 325 mg formulated as a single capsule or as separate monotherapies given in combination. Treatment periods were separated by a washout period of at least 6 days. The bioequivalence of a single-capsule formulation of esomeprazole 40 mg and ASA 325 mg relative to the monotherapies given individually was assessed by the geometric mean ratios of the area under the plasma concentration-time curve (AUC) and observed maximum plasma concentration (Cmax). If the 94% confidence interval (CI) of the geometric mean ratios of AUC and Cmax were within 0.80 - 1.25, bioequivalence would be established. A 94% CI was used to compensate for the multiple analyses of the study design, and to assure that the actual overall confidence level was 90%., Results: The geometric mean ratios of the AUC for esomeprazole 40 mg and ASA 325 mg when administered in the single capsule formulation, relative to the monotherapies were 0.97 (94% CI, 0.90 - 1.04) and 1.04 (94% CI, 1.00 - 1.08). The corresponding mean geometric ratios for Cmax were 0.99 (94% CI, 0.90 - 1.09) and 1.02 (94% CI, 0.92 - 1.13)., Conclusions: Treatment with esomeprazole 40 mg and ASA 325 mg formulated as a single capsule is bioequivalent to the separate monotherapies of esomeprazole 40 mg and ASA 325 mg when given in combination as separately-administered drugs in healthy adult subjects.

Background: Low-dose acetylsalicylic acid (ASA; 75-325 mg) is a mainstay of therapy for patients at high risk of cardiovascular (CV) events. However, in some patients, such treatment is associated with upper gastrointestinal (GI) adverse effects, e.g. dyspeptic symptoms, peptic ulceration, and GI bleeding, that may interfere with adequate adherence to, and continuation of, low-dose ASA for CV protection., Objective: The objective of this study was to explore the extent of, and drivers for, poor adherence to, and discontinuation of, low-dose ASA treatment for CV protection among a representative sample of patients in the US with GI problems., Methods: An online questionnaire was completed by eligible US adult patients (aged ≥20 years) who had been recommended low-dose ASA by a healthcare professional for secondary CV prevention or high-risk primary CV prevention (defined as diabetes mellitus or three or more risk factors for CV disease) and had experience of upper GI problems. Participants were asked questions about their demographic profile, general health, and attitudes towards low-dose ASA use. Patients were classified as 'lapsers' if they reported no longer regularly taking low-dose ASA; patients were also asked if they ever took deliberate, short-term breaks from their low-dose ASA regimen ('breakers'). Statistical analysis was descriptive., Results: From 56 296 invitation emails that were sent out, 1007 questionnaires were completed in full and were eligible for the analysis. The main reason for ineligible responses was unread emails. Respondents had a mean age of 52 years and 59% were women. Some 57% of patients were categorized as being at high primary CV risk and 43% were categorized as secondary CV prevention patients. A total of 67% of all patients used ASA at a daily dose of 81 mg. Overall, 28% of patients were considered to be poorly adherent through lapsing and/or taking deliberate, short-term breaks, and those receiving low-dose ASA for secondary CV prevention were more likely to be poorly adherent than were high-risk primary CV prevention patients (32% vs 25%). Of the overall population, 15% were lapsers (12% of secondary and 18% of high-risk primary CV prevention patients). The most common spontaneously reported reasons for lapse of low-dose ASA therapy were contraindicated combinations of medications and 'stomach problems'. Deliberate, short-term breaks from treatment were reported by 19% of all patients (24% of secondary and 15% of high-risk primary CV prevention). The most common spontaneously reported reasons for breaks were 'stomach problems' and preparation for surgery. Overall, 88% of patients reported experiencing heartburn or acid reflux symptoms. Self-reported rates of GI problems were greater in secondary than in high-risk primary CV prevention patients., Conclusion: Among the US cohort studied (i.e. low-dose ASA users with experience of upper GI problems), poor adherence to low-dose ASA treatment for both secondary and high-risk primary CV prevention was common.

Long-term therapy with low-dose aspirin (acetylsalicylic acid; ASA), 75-325 mg, is highly effective for the secondary prevention of cardiovascular (CV) events. For high-CV-risk patients to attain the full benefits of this therapy, it is important that treatment is continuous and that good compliance is maintained over the long term. We aimed to quantify the level of, and investigate the reasons for, patient-driven non-compliance and treatment discontinuation among patients taking low-dose ASA for the prevention of CV events. We therefore performed a systematic search of the PubMed, Embase, and Cochrane databases using the terms 'aspirin' AND 'patient compliance' OR 'withdrawal', with no restrictions on the start date and up to July 2008. A total of 32 studies, summarizing >144 800 patients, were selected from over 400 results for inclusion. Poor compliance (defined differently among the studies included) with low-dose ASA therapy ranged from approximately 10% to over 50%, and patient-initiated discontinuation of therapy occurred in up to 30% of patients. Common predictors of both non-compliance and treatment discontinuation were lower education level, female sex, or a history of depression, diabetes mellitus, or cigarette smoking. Adverse events were cited as the reason for low-dose ASA discontinuation in almost 50% of patients. The findings of this review suggest that poor compliance is common among patients receiving low-dose ASA therapy, placing them at substantial risk of CV events. By addressing barriers to compliance with low-dose ASA therapy, healthcare professionals can improve CV risk management for such patients.

Background: While low-dose acetylsalicylic acid (ASA [aspirin]; 75-325 mg) is a mainstay of cardiovascular (CV) protection in patients at high risk of CV events, such protection may be compromised due to poor adherence (or discontinuation) resulting from gastrointestinal (GI) adverse events. To date, however, the link between GI adverse events and nonadherence to, and discontinuation of, low-dose ASA is not well established in the literature., Objective: The aim of this study was to characterize the real-world impact of upper GI symptoms on low-dose ASA nonadherence and discontinuation in patients with CV risk taking low-dose ASA for CV protection., Study Design: Multicenter, observational, noninterventional study., Setting: Primary-care, cardiology, and practice group centers in the US, Canada, and France., Patients: Subjects aged ≥18 years at risk of, or with confirmed, CV disease, and who had been prescribed or recommended low-dose ASA (75-325 mg daily) by a physician., Main Outcome Measure: Adherence to low-dose ASA was assessed using 3 months of data prospectively collected using an electronic diary (completed at least three times/day). Adherence was defined as low-dose ASA intake of ≥75% over the 3-month eDiary phase. Discontinuation was defined as no reported low-dose ASA intake for ≥7 continuous days. The odds of daily adherence were calculated using a mixed-model analysis for repeated measures, and a Cox-proportional hazard model was used to assess the association between upper GI symptoms and time to discontinuation of low-dose ASA., Results: Overall, 340 patients (mean age 50 years; 59% women) participated in the analysis. Most patients (75%) were low-dose ASA naïve at inclusion, and had not experienced upper GI symptoms within the previous 14 days. Among these patients, the onset of upper GI symptoms was rapid; symptoms were reported by 19% of patients on the first day of the study, rising to 46% of patients at the end of the first week. Over the 3-month study period, 18% of patients were nonadherent to low-dose ASA treatment. The occurrence of upper GI symptoms negatively affected low-dose ASA adherence, in both the overall patient population (odds ratio [OR] = 0.84; 95% CI 0.70, 1.0) and among patients who were low-dose ASA naïve at baseline (OR = 0.76; 95% CI 0.57, 1.0). A total of 13% of patients discontinued low-dose ASA therapy. For the overall cohort and for the low-dose ASA-naïve patients at baseline, more than three episodes of upper GI symptoms during the previous week was associated with an increased risk of low-dose ASA discontinuation compared with no episodes of upper GI symptoms during the previous week (hazard ratio [HR] = 2.60; 95% CI 1.00, 6.80, and HR = 7.52; 95% CI 2.57, 22.04, respectively)., Conclusions: Upper GI symptoms can lead to nonadherence to, and discontinuation of, low-dose ASA CV-protective therapy. Patients who initiate low-dose ASA may experience an early onset of upper GI symptoms. (, Trial Registration Number: NCT00681759 [ClinicalTrials.gov Identifier]; AstraZeneca study code: D961FC00004).

Background: Gastroduodenal ulcers are common in patients taking low-dose aspirin. However, the factors predisposing to mucosal erosions, the precursor lesions, are not well known., Aims: To examine the potential risk factors for the development of erosions in patients chronically taking low-dose aspirin., Methods: Patients included were taking aspirin 75-325 mg daily for >28 days. Exclusion criteria included use of nonsteroidal anti-inflammatory and ulcer-healing drugs. Demographic data were collected at baseline, prior to endoscopy to determine the frequency and number of erosions and Helicobacter pylori status. In those without ulcer or other exclusions, endoscopy was repeated at 3 months., Results: Fewer patients had gastric erosions if they were H. pylori +ve (48.5% vs. 66.4% in H. pylori-ve patients at baseline, P = 0.17; 40.0% vs. 64.1% at 3 months, P = 0.029). If gastric erosions were present, they were also less numerous in H. pylori +ve patients (3.61 +/- 0.83 vs. 4.90 +/- 0.53 at baseline, P = 0.026; 2.17 +/- 0.68 vs. 5.68 +/- 0.86 at 3 months, P = 0.029). There was a trend (0.1 > P > 0.05) for more gastric erosions in those taking >100 mg/day aspirin. Males had more duodenal erosions at baseline (25.2% vs. 7.5%, P = 0.016). Patient age did not affect the presence or number of erosions. H. Pylori was not significantly associated with duodenal erosion numbers., Conclusions: Helicobacter pylori infection may partially protect against low-dose aspirin-induced gastric erosions; damage to the stomach appears weakly dose-related; and older age does not increase the risk of erosions.

Background: Low-dose acetylsalicylic acid (ASA; aspirin; 75-325 mg/day) is effective for the prevention of cardiovascular events, and its use in this indication is rapidly increasing. However, the use of ASA and, indeed, other non-steroidal anti-inflammatory drugs (NSAIDs) is limited by the incidence of adverse gastroduodenal events. OBJECTIVES AND SCOPE: To review the clinical evidence for, and the pharmacodynamic basis of, ASA-induced gastroduodenal toxicity in comparison with NSAIDs, and address the question of whether low-dose ASA is 'safe' from a gastroduodenal perspective. This was a narrative, descriptive review, rather than a formal systematic review., Findings: Adverse gastroduodenal effects, which are well known to occur with NSAIDs, are also prevalent in patients receiving low-dose ASA for cardiovascular protection even at doses as low as 75 mg/day. The risk of gastroduodenal toxicity is particularly high among 'at-risk' low-dose ASA patients (aged >70 years, previous ulcer or upper gastrointestinal bleeding and users of antiplatelets or NSAIDs). There are important differences in the mechanism of ASA-induced gastroduodenal toxicity, relative to NSAIDs. These differences include the effects on the cyclooxygenase (COX)-1 isoenzyme, local effects on the gastroduodenal mucosa specific to ASA and a reduction in platelet aggregation., Conclusion: Data suggest that ASA causes significant gastroduodenal damage even at the low doses used for cardiovascular protection. These effects (both systemic and possibly local) may be pharmacodynamically distinct from the gastroduodenal toxicity seen with NSAIDs. Studies are required to establish strategies for improving the tolerability of low-dose ASA, allowing patients to continue to benefit from the cardiovascular protection associated with such therapy.

Objective: To evaluate the effect of esomeprazole on the pharmacokinetics of low-dose acetylsalicylic acid (ASA) during repeated co-administration., Methods: This was an open, randomized, 3-way crossover study in 55 healthy volunteers. Treatment periods comprised 5 days' oral esomeprazole (40 mg) or ASA (325 mg) alone, or in combination, separated by washout of >or= 13 days. The primary pharmacokinetic end points were steady-state area under the concentration-time curve (AUCtau) and observed maximum plasma concentration (Cmax) of ASA +/- esomeprazole., Results: The estimates (90% confidence interval) of the geometric mean ratios for AUCtau and Cmax of ASA +/- esomeprazole were 1.04 (1.00 - 1.09) and 1.12 (1.03 - 1.22), respectively. Corresponding results for esomeprazole +/- ASA were 0.93 (0.89 - 0.98) and 0.96 (0.91 - 1.01), respectively. Administration of esomeprazole and ASA in combination was well tolerated., Conclusions: There was no pharmacokinetic interaction between esomeprazole (40 mg) and ASA (325 mg) during repeated co-administration in healthy volunteers.

Background: Aspirin is valuable for preventing vascular events, but information about ulcer frequency is necessary to inform risk-benefit decisions in individual patients., Aim: To determine ulcer prevalence and incidence in a population representative of those given aspirin therapy and evaluate risk predictors., Methods: Patients taking aspirin 75-325 mg daily were recruited from four countries. Exclusions included use of gastroprotectant drugs or other non-steroidal anti-inflammatory drugs. We measured point prevalence of endoscopic ulcers, after quantitating dyspeptic symptoms. Incidence was assessed 3 months later in those eligible to continue (no baseline ulcer or reason for gastroprotectants)., Results: In 187 patients, ulcer prevalence was 11% [95% confidence interval (CI) 6.3-15.1%]. Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer. Ulcer incidence in 113 patients followed for 3 months was 7% (95% CI 2.4-11.8%). Helicobacter pylori infection increased the risk of a duodenal ulcer [odds ratio (OR) 18.5, 95% CI 2.3-149.4], as did age >70 for ulcers in stomach and duodenum combined (OR 3.3, 95% CI 1.3-8.7)., Conclusions: Gastroduodenal ulcers are found in one in 10 patients taking low-dose aspirin, and most are asymptomatic; this needs considering when discussing risks/benefits with patients. Risk factors include older age and H. pylori (for duodenal ulcer).