Co-prescription Of Proton Pump Inhibitors Research Articles

Rational use of prescribing power of a physician

Abstract Writing a prescription is a duty, responsibility and a power has to be used diligently. For various reasons, our prescription sometimes becomes longer than necessary. Multiple medications can be associated with adverse outcome. Co-prescription of proton pump inhibitors with analgesics and probiotics with antibiotics may not be required routinely. Human chorionic gonadotrophin for threatened abortion deserves a relook. Progesterone during pregnancy has been overstretched. Vitamins supplementation has its place only in specific situations but tends to be over-prescribed. A rational approach while prescribing would be scientific as well as pocket-friendly to the patient.

Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Recurrent Stroke and Myocardial Infarction.

Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). This study used two databases for two different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS data base converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study based on large-scale propensity score matching. In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1216 patients with history of MI within1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 (95% confidence interval (CI); 1.83-2.38); the RR showed an increasing trend parallel to the time from the beginning of PPI co-prescription. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group (Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, p = 0.04). The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, p = 0.23). The impact of individual PPIs on stroke and MI showed different patterns. A PPI co-prescription >4 weeks with clopidogrel was associated with hospitalization of recurrent stroke within 1 year of initial diagnosis; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.

The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis.

Introduction: Proton pump inhibitors (PPIs) are one of the most prescribed classes of drugs worldwide as a first-line treatment of acid-related disorders. Although adverse effects are rare and rapidly reversible after a short exposure, concerns have been recently raised about a greater toxicity on cardiovascular health after a longer exposure, especially when combined with clopidogrel. We aimed to evaluate the safety of long-term PPI use on cardiovascular health in patients with known atheromatous cardiovascular disease. Methods: A literature search was conducted in the PubMed, Embase, and Cochrane Library databases and grey literature in April 2022. Articles published between 2014 and 2022 were considered relevant if they were designed as randomized controlled trials (RCTs) that included post hoc analyses or prospective observational studies and if they investigated clinical cardiovascular outcomes associated with PPI use for 6 months or more in patients suffering from cardiovascular disease requiring antiplatelet agent therapy and/or coronary angioplasty. Statistical analyses were performed using RevMan 5.4 software (Computer program, the Cochrane Collaboration, 2020, London, UK). The risk of bias was assessed using the Cochrane risk-of-bias tool for the RCTs and the Newcastle–Ottawa scale for the observational studies. Results: A total of 10 full-text articles involving 53,302 patients were included. Substantial heterogeneity was found among the 10 included studies. The primary analysis showed no significant differences between the PPI group and the control group for the risks of major adverse cardiovascular events (MACEs), all-cause death (ACD), or target vessel revascularization (TVR) using a random-effects model (OR 1.15, 95% CI 0.98–1.35, p = 0.08, I2 = 73%; OR 1.24, 95% CI 0.94–1.65, p = 0.13, I2 = 63%; and OR 1.19, 95% CI 0.76–1.87, p = 0.45, I2 = 61%, respectively). The primary analysis yielded similar results for the risks of myocardial infarction (MI), stroke, and cardiovascular death (CVD) using a fixed-effects model (OR 0.98, 95% CI 0.88–1.09, p = 0.66, I2 = 0%; OR 1.02, 95% CI 0.90–1.17, p = 0.73, I2 = 0%; and OR 1.04, 95% CI 0.94–1.16, p = 0.44, I2 = 35%, respectively). Likewise, a subgroup analysis based on eight randomized controlled trials failed to identify any association between PPI use and the risks of MACEs, MI, stroke, TVR, ACD, or CVD using a fixed-effects model (overall pooled OR 1.01, 95% CI 0.96–1.06; p = 0.66; I2 = 0%). The pulled data from the two included observational studies (OS) demonstrated a significantly increased risk of MACEs in the PPI group (OR 1.42, 95% CI [1.29–1.57], p <0.001; I2 = 0%). In another subgroup analysis, no evidence of an increased risk of adverse cardiovascular events in the co-therapy PPI/clopidogrel versus clopidogrel alone groups was found with the exception of the risk of ACD (OR 1.50, 95% CI 1.23–1.82, p = 0.001, I2 = 0%). Nevertheless, after performing a sensitivity analysis reaching heterogeneity I2 = 0%, the co-prescription of PPIs and clopidogrel was at increased risk of MACEs (p < 0.001), CVD (p = 0.008), and TVR (p < 0.001) but remained statistically non-significant for the risk of MI (p = 0.11). Conclusions: The overall results of this meta-analysis showed that long-term PPI use was not associated with an increased risk of adverse cardiovascular events. However, inconsistent results were found for combined PPI/clopidogrel therapy. These results should be considered with caution in light of the significant heterogeneity, the limited number of included studies, and the lack of adjustment for potential confounders.

Low-dose aspirin for the prevention of atherothrombosis across the cardiovascular risk continuum

Abstract At the 2021 International Aspirin Foundation Symposium of Oriental Congress of Cardiology, a panel of distinguished cardiologists from around the world gathered to present their recent research findings and discuss viewpoints of aspirin use along the entire continuum of cardiovascular disease (CVD) prevention in the general population as well as in specific patient groups. Aspirin produces long-lasting effects on platelet function and cumulative inhibition of platelet thromboxane production by irreversibly inactivating the prostaglandin H-synthase (PGHS). Consistent with saturability of platelet cyclooxygenase 1 (COX-1) inactivation and thromboxane A2 (TXA2) suppression at low doses, a body of convincing evidence showed no additional benefit from high versus low-dose aspirin. Trials of aspirin as primary prevention trials are challenging due to the low event rate and reduced patient compliance over time. Nevertheless, evidence from the ASCEND and TIPS3 trials supported the benefit of aspirin in primary cardiovascular prevention. The Chinese population has among the highest CVD risk in the world. Significant achievement has been made in this respect. For example, the benefit of aspirin use as primary prevention is now recognized in the Chinese guidelines similar to the US, European guidelines, with some unique features that are helpful for the Chinese population (eg, greater emphasis on dynamical reassessment of risk versus benefit). As secondary prevention in patients with transient ischaemic attack (TIA) and minor stroke, low-dose aspirin reduces the risk of major recurrent stroke as well as stroke severity. Peripheral arterial disease (PAD) management and screening is of growing importance. The COMPASS and VOYAGER studies provide new evidence for dual-pathway inhibition (DPI) antithrombotic therapy with low-dose aspirin and reduced-dose rivaroxaban. A major concern with the use of aspirin is the risk of gastrointestinal (GI) bleeding. Strategies to protect patients include eradication of Helicobacter pylori infection and co-prescription of proton pump inhibitors. Different P2Y12 inhibitors and low-dose aspirin have similar levels of bleeding risk, but the risk is magnified when these agents are taken together.

GASTROPROTECTION IN PATIENTS ON ANTITHROMBOTIC THERAPY: A QUALITY IMPROVEMENT STUDY

GASTROPROTECTION IN PATIENTS ON ANTITHROMBOTIC THERAPY: A QUALITY IMPROVEMENT STUDY

Antiplatelet therapy for transient ischaemic attacks and acute minor strokes: current best practice and future

In patients presenting with transient ischaemic attacks and acute minor noncardioembolic ischemic strokes (NIHSS score ≤3) who did not receive intravenous alteplase, treatment with dual antiplatelet therapy with aspirin and clopidogrel, started within 24 hours of symptom onset and continued for 21 days is effective in reducing a recurrent ischemic stroke up to 90 days from the symptom onset. However, as the long-term risk of major disabling bleeding with aspirin-based antiplatelet treatment is higher in patients aged 75 years or older, routine co-prescription of proton pump inhibitor should be encouraged.

Prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) among community patients with musculoskeletal and co-morbid conditions: A crosssectional study from an Iraqi province

Purpose: To determine the pattern of prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) co-prescription with NSAIDs in a sample of patients suffering from musculoskeletal disorders with and without co-morbid cardiovascular (CV) disease conditions in Baghdad Province, Iraq.Methods: A descriptive, cross-sectional study was conducted using a structured questionnaire to assess the clinical characteristics of patients that used NSAIDs alone or with PPIs for the treatment of different musculoskeletal disorders with and without co-morbid cardiovascular (CV) disease conditions.Results: A total of 102 participants were enrolled in the study. More than half of the participants had comorbid disease conditions (53.9 %), particularly hypertension (47.1 %). Nearly a quarter of the participants with CV disease conditions used non-selective NSAIDs (25.5 %). The majority of NSAIDs intake were orally administered for more than one month (79.4 %). Physicians were the major source for patient education about the risk of NSAIDs-associated complications according to 59.6 % of the participants. The majority of participants reported non-adherence to the prescribed PPIs (86.5 %). There was a statistically significant difference between the participants that used NSAIDs alone, and those with PPI co-prescription within the age group of 31 - 60 years (p &lt; 0.0001) and for a duration of more than one month for NSAIDs administration (p &lt; 0.0001).Conclusion: There is improper use of NSAIDs, particularly the non-selective agents, among patients with co-morbid cardiovascular disease conditions, as well as poor medication adherence and improper co-prescription of PPIs. This requires periodic revision for long-term intake of NSAIDs, while applying more care to high-risk patients regarding co-prescription of NSAIDs with PPIs.&#x0D; Keywords: Cardiovascular, Co-morbidity, Gastrointestinal complications, NSAIDs, Proton-pump inhibitors

Major gastrointestinal bleeding and antithrombotics: Characteristics and management.

BACKGROUNDThere are few reports on major gastrointestinal (GI) bleeding among patients receiving an antithrombotic.AIMTo describe clinical characteristics, bleeding locations, management and in-hospital mortality related to these events.METHODSOver a three-year period, we prospectively identified 1080 consecutive adult patients admitted in two tertiary care hospitals between January 1, 2013 and December 31, 2015 for major GI bleeding while receiving an antithrombotic. The bleeding events were medically validated. Clinical characteristics, causative lesions, management and fatalities were described. The distribution of antithrombotics prescribed was compared across the bleeding lesions identified.RESULTSOf 576 patients had symptoms of upper GI bleeding and 504 symptoms of lower GI bleeding. No cause was identified for 383 (35.5%) patients. Gastro-duodenal ulcer was the first causative lesion in the upper tract (209 out of 408) and colonic diverticulum the first causative lesion in the lower tract (120 out of 289). There was a larger proportion of direct oral anticoagulant use among patients with lower GI than among those with upper GI lesion locations (P = 0.03). There was an independent association between gastro-duodenal ulcer and antithrombotic use (P = 0.03), taking account of confounders and proton pump inhibitor co-prescription. Pair wise comparisons pointed to a difference between vitamin K antagonist, direct oral anticoagulants, and antiplatelet agents in monotherapy vs dual antiplatelet agents.CONCLUSIONWe showed a higher rate of bleeding lesion identification and suggested a different pattern of antithrombotic exposure between upper and lower GI lesion locations and between gastro-duodenal ulcer and other identified upper GI causes of bleeding. Management was similar across antithrombotics and in-hospital mortality was low (5.95%).

Costs of bleeding on long-term antiplatelet treatment without routine co-prescription of proton-pump inhibitors.

Long-term antiplatelet treatment is associated with major bleeding. To determine the costs associated with major bleeding in patients treated with aspirin-based antiplatelet treatment for secondary prevention of vascular events without routine prescription of proton-pump inhibitors and to estimate the likely long-term savings from routine co-prescription. In a prospective population-based cohort study of TIA, ischemic stroke, and MI treated with antiplatelet drugs, we evaluated hospital care costs associated with bleed management during 10-year follow-up. Bleeding-associated costs were averaged across all patients. For upper GI-bleeds, mean costs were compared with the cost of routine co-prescription of proton-pump inhibitor. Among 3166 patients on antiplatelet therapy with 405 first bleeding events, the average cost of major bleeding was $13,093 (S.D. 20,501), with similar costs for upper GI bleeds and intracranial bleeds (p = 0.235). However, total costs among the 3166 patients were higher for upper GI bleeds ($1,158,385 vs. $740,123). Averaged across all patients, the 10-year cost of major bleeding was $838 (95%CI: 680-1007), $411 due to upper GI bleeding, the cost of which increased from $175 in those aged <75 years to $644 at age ≥75 years (p < 0.0001). The corresponding costs of routine life-long co-prescription of proton-pump inhibitor to those patients not on prior treatment were $85 (84-88) and $39 (38-42). In secondary prevention with aspirin-based antiplatelet treatment without routine proton-pump inhibitor use, the long-term costs of upper-GI bleeding at age ≥75 years are much higher than at younger age groups, and are at least 10-fold greater than the drug cost of routine co-prescription of proton-pump inhibitor.

Modification of gastric cancer risk associated with proton pump inhibitors by aspirin after Helicobacter pylori eradication.

AimAlthough proton pump inhibitors (PPIs) can prevent aspirin-induced upper gastrointestinal bleeding, a clinical dilemma exists as long-term use of PPI may also increase the risk of gastric cancer even after Helicobacter pylori (HP) eradication. We aimed to investigate the potential interaction between aspirin and PPIs on GC risk in patients who have HP eradicated.ResultsOf the 63,397 HP eradicated subjects (median follow-up 7.6 years), 153 (0.24%) developed GC. PPIs were associated with a higher GC risk among non-aspirin users (aHR: 3.73, 95% CI:2.11–6.60) but not among aspirin users (aHR: 0.35, 95% CI:0.04–2.74).Materials and MethodsThis is a post-hoc analysis based on a previously published territory-wide retrospective cohort study on the potential risk of PPIs on GC. Adults who had received an outpatient prescription of clarithromycin-based triple therapy for HP between 2003 and 2013 were identified. The adjusted hazard ratio (aHR) of GC with PPIs, stratified according to aspirin use, was calculated by Cox model with propensity score adjustment of other covariates.ConclusionsThe potential harmful effects of PPIs on GC development appear to be limited to non-aspirin users. Co-prescription of PPIs is therefore recommended for HP-eradicated patients who are at risk of aspirin-induced UGIB.

Proton pump inhibitors are not associated with inflammatory myopathies: A case control study.

A rare association of proton pump inhibitor (PPI) use with the development of inflammatory myopathies (IM) has been reported, but, unlike with statin medications, there is limited data supporting or refuting this observation. A case-control study was conducted on patients with IM. Clinical information, medications, and demographics were recorded. Controls were matched 3:1 for age and gender. Two hundred twenty-one cases of IM were identified. No association of PPI use with IM was observed when compared with controls (odds ratio 1.04 [95% confidence interval 0.68-1.58]) and similar results were observed after adjusting for diabetes, cardiovascular disease, and statin exposure (adjusted odds ratio 1.084 [95% confidence interval 0.69-1.70]). There was no association of any histologic subtype of IM with PPI exposure. Our findings do not support an association of PPI exposure with IM. Co-prescription of PPI with other medications was not considered and could be further investigated with larger cohorts. Muscle Nerve 58:855-857, 2018.

Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis.

Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders. We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16; P<0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01-1.29; P=0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; P=0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04-1.61; P=0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03-1.47; P=0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93-1.52; P=0.16). Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines.

Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study

SummaryBackgroundLifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70–90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages.MethodsWe did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials.Findings3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27–4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65–11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60–6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37–24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67–12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older.InterpretationIn patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.FundingWellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre.

Proton pump inhibitor co-prescription with dual antiplatelet therapy among patients with acute coronary syndrome in Qatar.

There are increasing concerns about clinically significant interactions between proton pump inhibitors (PPIs) and clopidogrel, resulting in adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). However, published evidence on the prevalence and predictors of PPI use with dual antiplatelet therapy (DAPT) is scarce. This study investigated the prevalence of PPI use among patients with ACS receiving DAPT and possible predictors of co-prescribing the PPIs with the DAPT. Heart Hospital, a specialized tertiary care center in Qatar. A retrospective observational study of a prescription database was conducted. Subjects included 626 patients admitted between January and December 2012 with the diagnosis of ACS who received DAPT and discharged with or without a PPI. Univariate analysis and multivariate binary logistic regression analysis were performed to determine the predictors of PPI-DAPT co-prescription. Prevalence of PPI co-prescribing with DAPT in proportions and percentages and odd ratios for the predictors of PPI-DAPT co-prescribing. A total of 626 patients were analyzed for PPI prevalence, with 200 patients (32 %) being prescribed PPI with DAPT upon discharge. After controlling for confounders, PPI use on admission (aOR 14.5; 95 % CI 7.6-27.6, p < 0.001), nationality (aOR 3.2; 95 % CI 1.1-9.9, p = 0.041), and having a history of diabetes (aOR 0.5; 95 % CI 0.24-0.99, p = 0.046) significantly influenced PPI-DAPT co-prescribing. Users of PPI on admission compared to nonusers were about 15 times more likely to be prescribed PPI with DAPT upon discharge; likewise, having Qatari nationality increased the likelihood of co-prescribing PPI with DAPT upon discharge by three folds. Lastly, patients with a history of diabetes were 50 % less likely to be prescribed PPIs upon discharge compared to those with no history of diabetes. The rate of PPI co-prescribing with DAPT in the population studied was relatively high. The strongest predictor of PPI co-prescription with DAPT upon discharge was PPI use on admission. Furthermore, PPI prescribing was significantly predicted by nationality and not having diabetes. Further studies are warranted to better predict the factors associated with PPI-DAPT co-prescription and to investigate rational prescribing of PPIs among ACS patients.

Gastrointestinal risk assessment in patients requiring non-steroidal anti-inflammatory drugs for osteoarthritis: The GIRANO study.

To evaluate gastrointestinal risk profiles in patients with osteoarthritis who are currently being treated, or who are candidates for treatment, with a non-steroidal anti-inflammatory drug. Patients with osteoarthritis treated by primary care physicians or physical and rehabilitation medicine (PRM) specialists in Belgium and Luxembourg were scored for gastrointestinal risk profile, low, moderate or high, based on the presence of gastrointestinal risk factors. These included advanced age, gastrointestinal history, comorbidities, medication use, smoking, and alcohol consumption. Use of gastro-protective agents (proton pump inhibitors) was also assessed. A total of 190 primary care physicians and PRM specialists provided data on 885 patients. A large majority of patients were rated high-risk gastrointestinal (77.8%), with fewer moderate (19.4%) or low (2.8%) risk. The proportion of high-risk patients treated by PRM specialists was significantly lower than that treated by primary care physicians (64.7% vs 79.9%; p < 0.0001). Only 37.0% of high-risk patients received proton pump inhibitors co-prescription with a non-steroidal anti-inflammatory drug. A high prevalence of elevated gastrointestinal risk was found in this survey of patients with osteoarthritis who were current or candidate users of non-steroidal anti-inflammatory drugs. This appears to be insufficiently recognized, as preventative gastro-protective co-treatment was infrequently prescribed. Careful assessment of gastrointestinal risk factors should be made before prescribing non-steroidal anti-inflammatory drugs, with treatment tailored to the patient's gastrointestinal risk profile.

Trends in the coprescription of proton pump inhibitors with clopidogrel: an ecological analysis.

In early 2009, 2 observational studies and a US Food and Drug Administration (FDA) advisory addressed the drug interaction between proton pump inhibitors (PPIs) and clopidogrel. One study suggested that pantoprazole could be used safely in this setting, whereas the other study and the FDA advisory did not distinguish among PPIs. We examined trends in PPI prescribing among clopidogrel recipients in the period following these events. We conducted a population-based time series analysis of Ontario residents aged 66 years or older for whom clopidogrel was prescribed between Apr. 1, 1999, and Sept. 30, 2013. We determined the proportion of clopidogrel recipients dispensed a PPI during each quarter and the proportions who received pantoprazole or other PPIs. The outcome of interest was change in the use of pantoprazole. In the final quarter of 2008, pantoprazole represented 23.7% of all PPI prescriptions dispensed to patients receiving clopidogrel. Following the publications and FDA advisory in early 2009, pantoprazole use increased substantially. By the end of 2009, this medication accounted for 52.5% of all PPI prescriptions issued to patients receiving clopidogrel; by the end of the study period, it accounted for 71.0% of all PPI prescriptions dispensed to such patients (p < 0. 001). We also observed a modest drop in overall PPI use among clopidogrel recipients beginning in early 2009. In 2009, the prescribing of PPIs with clopidogrel changed substantially in Ontario, with pantoprazole rapidly becoming the most commonly prescribed agent in its class. However, a modest decline in overall PPI use also occurred that may reflect suboptimal translation of emerging drug safety information to clinical practice.

Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between H. pylori Infection and Low-Dose Aspirin Use.

Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co-prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive lowdose aspirin users without histories of peptic ulcers remains to be clarified.

PWE-188 Do proton pump inhibitors prevent upper gastrointestinal bleeding in patients treated for acute coronary syndrome?

Introduction NICE recommends dual anti-platelet therapy (DAPT) for 12 months following an acute coronary syndrome (ACS). 1 DAPT carries a risk of gastrointestinal (GI) bleeding. The incidence and outcome of patients who have a GI bleed whilst taking DAPT are not well known and despite recommendations, the protective effects of proton pump inhibitors (PPIs) in this group are debated. 2 We studied readmission rates with UGI bleeding and subsequent outcomes in ACS patients for one year following their event. We analysed data to ascertain whether there was any benefit to co-prescription of PPI with DAPT. Method Data were collected using the Northumbria Myocardial Infarction National Audit Project (MINAP) database, for the calander year 2012. We analysed 12 month readmission rates with GI bleeding and subsequent outcomes; including endoscopic findings, the use of PPI, mortality data and age demographics. Results 585 patients suffered an ACS in our study population. 12 patients (2%) were readmitted with GI bleeding within the first year. Nine patients were male, with a median age of 82 years, and three were female: median age 90 years. Lansoprazole (a PPI) 30mg daily was prescribed for 8/12 (66%) patients. Seven patients (58%) died; two directly as a consequence of GI bleeding and five due to subsequent complications. In those taking a PPI the mortality rate was 50% (4/8). In the non-PPI group the mortality rate was higher at 75% (3/4). Regarding UGI endoscopy; four patients did not undergo intervention on clinical grounds. In those who underwent upper GI endoscopy, diagnoses included: oesophagitis, gastritis, duodenal ulceration, gastric ulceration, oesophageal ulceration and possible bleeding Dieulafoy lesion. In two patients, no cause for bleeding was found. Considering those aged 80 or older; 227 patients suffered an ACS. Nine of these were readmitted with GI bleeding (4%) with only two patients surviving that admission (mortality rate 78%). In the 358 patients under the age of 80, the risk of re-admission with GI bleed was 0.8% and the mortality rate was zero. Conclusion The risk of readmission with GI bleeding in the first year following ACS whilst on DAPT is low (2%). The protective effects of PPIs in GI bleeding in patients taking DAPT have not been demonstrated by this study. However, we note a higher mortality rate in the non-PPI group. Patients over 80 years old have a poor outcome and higher mortality rate despite prescription of PPI. Treatment decisions for this specific group should be carefully considered. Disclosure of interest None Declared. References NICE. Antiplatelet treatment:secondary prevention of CVD http://cks.nice.org.uk/antiplatelet-treatment Moukarbel GV, et al . Gastrointestinal bleeding in high risk survivors of myocardial infarction. Eur Heart J. 2009;30:2226–2232

15 Incidence and Outcome from Upper GI Haemorrhage in the First Year following an Acute Coronary Syndrome

<h3>Introduction</h3> NICE recommends dual anti-platelet therapy (DAPT) for 12 months following an acute coronary syndrome (ACS). DAPT carries a risk of significant bleeding particularly from the GI tract. The incidence and outcome of patients who have a GI bleed whilst taking DAPT is not well known and despite the recommendations, the protective effects of proton pump inhibitors (PPI) in ACS patients receiving DAPT are debated and robust evidence is lacking. We studied readmission rates with UGI bleeding and subsequent outcomes in ACS patients for the first year following their event. We recorded the incidence and outcome to ascertain whether there was any benefit to co-prescription of PPI with DAPT. <h3>Results</h3> 585 patients suffered an ACS during the calendar year 2012; recorded on the Northumbria NHS trust MINAP database. 12 patients (2%) were found to have been readmitted to the same trust with a diagnosis of GI haemorrhage within that 12 month period. Nine patients were male with a median age of 82 years; 3 were female, with a higher median age of 90 years. Lansoprazole (a PPI) 30 mg daily was prescribed for 8 out of 12 (66%) patients. Four patients were not prescribed a PPI. Seven patients (58%) died (mean age 85). Two patients died as a direct result of their GI haemorrhage and 5 died due to subsequent complications. In those taking a PPI the mortality rate was 50% (4 of 8 patients) and in those not taking a PPI the mortality rate was higher at 75% (3 out of 4 patients). Regarding UGI endoscopy; four patients did not undergo intervention as it was deemed inappropriate on clinical grounds. In those who underwent UGI endoscopy, diagnoses included: oesophagitis, gastritis, duodenal ulceration, gastric ulceration, oesophageal ulceration and a possible bleeding Dieulafoy lesion. In two patients, no cause for the bleeding was found. <h3>Conclusions</h3> The risk of readmission with upper GI haemorrhage in the first year following an ACS whilst on DAPT is low (2%). However, patients who are admitted are elderly and frail and have a poor outcome despite the prescription of PPI therapy. Shortening the duration of DAPT therapy in the elderly, particularly if medically treated should be considered.

Gastrointestinal symptoms in NSAID users in an ‘average risk population’: results of a large population-based study in randomly selected Dutch inhabitants

Non-steroidal anti-inflammatory drug (NSAID) use is widespread and associated with gastrointestinal symptoms and complications. The aims of this study were to assess (i) gastrointestinal symptoms in users of prescribed and over-the-counter (OTC) NSAIDs and (ii) proton pump inhibitor (PPI) co-prescription rates in NSAID users at increased risk for gastrointestinal complications. Surveys were sent to a randomly selected sample of the adult Dutch general population in December 2008. Questions included demographics, gastrointestinal symptoms, medication use and comorbidity. Main outcome measure was presence of gastrointestinal symptoms. A total of 18,317 surveys were returned (response rate 35%), of which 16,758 surveys were eligible for analysis. Of these, 3233 participants (19%) reported NSAID use. NSAID users more frequently reported gastrointestinal symptoms than persons not using NSAIDs (33% vs. 24%, p<0.01). Respondents who specified on prescription NSAID use (n=683) were older, reported more comorbidity, and experienced more gastrointestinal symptoms (41%) compared with OTC users (n=894, 33%, p<0.01). This difference was not statistically significant after adjustment for confounders (0.99, 95% CI 0.71-1.37). In respondents with an increased gastrointestinal risk profile, PPI co-prescription rates were 51% for on prescription users and 25% for OTC users. Prevalence of gastrointestinal symptoms was high in both prescribed and OTC NSAID users, emphasising the side effects of both types of NSAIDs. PPI co-prescription rates in NSAID users at risk for gastrointestinal complication were low.