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Lin K.J.,Harvard University | Lin K.J.,Jacobi Medical Center | Hernandezdiaz S.,Harvard University | Garcia Rodriguez L.A.,Spanish Center for Pharmacoepidemiologic Research
Gastroenterology | Year: 2011

Background & Aims: We investigated the effect of different prevention strategies against upper gastrointestinal bleeding (UGIB) in the general population and in patients on antithrombotic or anti-inflammatory treatments. Methods: We performed a population-based, nested, case-control study using The Health Improvement Network UK primary care database. From 2000 to 2007, we identified 2049 cases of UGIB and 20,000 controls. The relative risk (RR) of UGIB associated with various gastroprotective agents was estimated by comparing current use (defined as use within 30 days of the index date) with nonuse in the previous year, using multivariate logistic regression. Results: The adjusted RR of UGIB associated with current use of proton pump inhibitors (PPIs) for more than 1 month was 0.58 (95% confidence interval [CI], 0.420.79) among patients who received low-dose acetylsalicylic acid (ASA), 0.18 (95% CI, 0.040.79) for clopidogrel, 0.17 (95% CI, 0.040.76) for dual antiplatelet therapy, 0.48 (95% CI, 0.221.04) for warfarin, and 0.51 (95% CI, 0.340.78) for nonsteroidal anti-inflammatory drugs. The corresponding estimates for therapy with histamine-2receptor antagonists (H 2RAs) were more unstable, but tended to be of a smaller magnitude. In the general population, PPI use was associated with a reduced risk of UGIB compared with nonuse (RR, 0.80; 95% CI, 0.680.94); no such reduction was observed for H 2RAs or nitrates. Conclusions: PPI use was associated with a lower risk of UGIB in the general population and in patients on antithrombotic or anti-inflammatory therapy compared with nonuse of PPIs. The reduction in risks of UGIB was smaller in H 2RA than in PPI users. © 2011 AGA Institute. Source


Cea-Soriano L.,Spanish Center for Pharmacoepidemiologic Research | Johansson S.,Astrazeneca | Garcia Rodriguez L.A.,Spanish Center for Pharmacoepidemiologic Research
Epidemiology | Year: 2013

BACKGROUND:: Some recent reports suggest an increased risk of fractures with use of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), although results are inconsistent and a causal relationship has yet to be proven. As these acid-suppressive drugs may have uncommon adverse effects on the central nervous system (CNS), such as dizziness, we investigated whether their use is associated with falls as a possible mechanism for increasing fracture risk. METHODS:: A cohort study with nested case-control analysis and two validation strategies was performed using data from UK patients (aged 40-89 years) included in The Health Improvement Network database (2000-2008). Due to the large number of falls, a random sample of 20,000 cases was used for the analysis. RESULTS:: The overall incidence of falls per 1000 person-years was 13.0 (95% confidence interval [CI] = 12.9-13.1). After adjustment for potential confounders, there was no relationship between falls and current use of single PPIs (odds ratio [OR] = 0.95; 95% CI = 0.89-1.02) or H2RAs (OR = 1.01; 95% CI = 0.90-1.14); there was no relationship with dose or duration of treatment. Falls were associated with CNS disorders and treatment with various pharmacological agents including antiparkinson drugs (OR = 2.7; 95% CI = 2.2-3.3) and antiepileptics (OR = 2.1; 95% CI = 1.8-2.3). CONCLUSIONS:: There was no association between falls and use of PPIs or H2RAs. Any potential increase in the risk of fractures proposed to be associated with the use of acid-suppressive drugs is not via an increased risk of falls. Copyright © 2013 by Lippincott Williams & Wilkins. Source


Garcia Rodriguez L.A.,Spanish Center for Pharmacoepidemiologic Research | Cea Soriano L.,Spanish Center for Pharmacoepidemiologic Research | Hill C.,Oxford PharmaGenesis Ltd | Johansson S.,Astrazeneca
Neurology | Year: 2011

OBJECTIVES: Discontinuation of low-dose acetylsalicylic acid (ASA) therapy may increase the risk of ischemic events. This study evaluated the risk of ischemic stroke (IS) and TIA after low-dose ASA discontinuation in patients with cardiovascular disease or cerebrovascular disease. METHODS: The Health Improvement Network UK primary care database was used to identify a cohort of individuals aged 50-84 years with a first prescription for low-dose ASA (75-300 mg/day) for the secondary prevention of cardiovascular or cerebrovascular events in 2000-2007 (n = 39,512). Individuals were followed up for a mean of 3.4 years to identify cases of IS/TIA. Nested case-control analyses were used to assess risk factors for IS/TIA, including low-dose ASA discontinuation. RESULTS: The overall incidence of IS/TIA was 5.0 per 1,000 person-years (95% confidence interval [CI] 4.6-5.4). IS/TIA was significantly more common in patients with a previous diagnosis of cerebrovascular disease (relative risk [RR] 2.79; 95% CI 2.05-3.80) or atrial fibrillation (RR 1.71; 95% CI 1.28-2.29) than in those without these conditions. Compared with current users of low-dose ASA, those who discontinued treatment 31-180 days before the index date had a significantly increased overall risk of IS/TIA (RR 1.40; 95% CI 1.03-1.92). The most common reason for discontinuation was patient nonadherence. CONCLUSION: In patients prescribed low-dose ASA for the secondary prevention of cardiovascular or cerebrovascular events, discontinuation of low-dose ASA was associated with a 40% increase in the risk of IS/TIA compared with continuation of therapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that discontinuation of low-dose ASA is associated with a 40% increased risk of stroke within 31-180 days of discontinuation. ©2011 American Academy of Neurology. Source


Lin K.J.,Harvard University | De Caterina R.,University of Chieti Pescara | Garcia Rodriguez L.A.,Spanish Center for Pharmacoepidemiologic Research
Circulation: Cardiovascular Quality and Outcomes | Year: 2014

Background-The benefit-risk profile of low-dose aspirin in primary prevention of cardiovascular disease is unclear. We sought to quantify upper gastrointestinal bleeding (UGIB) risk associated with low-dose aspirin in secondary versus primary prevention patients. Methods and Results-We performed a population-based nested case-control study using The Health Improvement Network (THIN) Database between 2000 and 2007. We identified 2049 cases of UGIB and 20 000 controls, frequencymatched to the cases on age, sex, and calendar year, who were subdivided into primary (without previous cardiovascular disease) and secondary (with previous cardiovascular disease) prevention populations. We estimated the relative risk of UGIB associated with the use of low-dose aspirin by multivariate logistic regression. The UGIB risk in patients taking low-dose aspirin relative to nonusers was significantly higher in the primary (adjusted relative risk, 1.90; 95% confidence interval, 1.59-2.26) than in the secondary (relative risk, 1.40; 95% confidence interval, 1.14-1.72; P value for the difference=0.0014) prevention cohort. However, as the baseline risk of UGIB was lower in the primary than in the secondary prevention cohort, numbers needed to harm per 1 year of low-dose aspirin use were 601 and 391 for primary and secondary prevention, respectively. Conclusions-The relative risk of UGIB in patients taking low-dose aspirin is higher when used for primary than for secondary cardiovascular disease prevention, but this difference is more than compensated by the lower baseline risk in the primary prevention population. Such estimates are important for an assessment of the net clinical benefit in primary prevention. © 2013 American Heart Association, Inc. Source


Cea Soriano L.,Spanish Center for Pharmacoepidemiologic Research | Johansson S.,Astrazeneca | Stefansson B.,Astrazeneca | Rodriguez L.A.G.,Spanish Center for Pharmacoepidemiologic Research
Cardiovascular Diabetology | Year: 2015

Background: Diabetes and chronic kidney disease (CKD) are independent predictors of death and cardiovascular events and their concomitant prevalence has increased in recent years. The aim of this study was to characterize the effect of the estimated glomerular filtration rate (eGFR) and other factors on the risk of death and cardiovascular events in patients with type 2 diabetes. Methods: A cohort of 57,946 patients with type 2 diabetes who were aged 20-89 years in 2000-2005 was identified from The Health Improvement Network, a UK primary care database. Incidence rates of death, myocardial infarction (MI), and ischemic stroke or transient ischemic attack (IS/TIA) were calculated overall and by eGFR category at baseline. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Death, MI and IS/TIA cases were detected using an automatic computer search and IS/TIA cases were further ascertained by manual review of medical records. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for death, MI, and IS/TIA associated with eGFR category and other factors were estimated using Cox regression models adjusted for potential confounders. Results: Overall incidence rates of death (mean follow-up time of 6.76 years), MI (6.64 years) and IS/TIA (6.56 years) were 43.65, 9.26 and 10.39 cases per 1000 person-years, respectively. A low eGFR (15-29 mL/min) was associated with an increased risk of death (HR: 2.79; 95% CI: 2.57-3.03), MI (HR: 2.33; 95% CI: 1.89-2.87) and IS/TIA (HR: 1.77; 95% CI: 1.43-2.18) relative to eGFR≥60 mL/min. Other predictors of death, MI and IS/TIA included age, longer duration of diabetes, poor control of diabetes, hyperlipidemia, smoking and a history of cardiovascular events. Conclusions: In patients with type 2 diabetes, management of cardiovascular risk factors and careful monitoring of eGFR may represent opportunities to reduce the risks of death, MI and IS/TIA. © Cea Soriano et al.; licensee BioMed Central. Source

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