Spanish Center for Pharmacoepidemiologic Research

Madrid, Spain

Spanish Center for Pharmacoepidemiologic Research

Madrid, Spain

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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.


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.


Soriano L.C.,Spanish Center for Pharmacoepidemiologic Research | Bueno H.,Hospital General Universitario Gregorio Maranon | Lanas A.,University of Zaragoza | Lanas A.,CIBER ISCIII | Rodriguez L.A.G.,Spanish Center for Pharmacoepidemiologic Research
Thrombosis and Haemostasis | Year: 2013

It was the aim of this study to investigate whether low-dose acetylsalicylic acid (ASA) therapy for secondary cardiovascular prevention should continue, despite the risk of gastrointestinal bleeding. We aimed to make a clinically meaningful benefit-risk assessment regarding the cardiovascular and gastrointestinal consequences of ASA discontinuation.This case-control study usedThe Health Improvement Network UK primary care database to identify patients aged 50-84 years during 2000-2007 with a first ASA prescription for secondary cardiovascular prevention (N = 39,513). New cases of non-fatal myocardial infarction (MI)/coronary death (n = 1,222), ischaemic stroke (IS)/transient ischaemic attack (TIA) (n = 673) and upper gastrointestinal bleeding (UGIB) (n = 169) were identified after a mean follow-up of 3.2, 3.4 and 4.0 years, respectively. ASA discontinuers before the index date were identified. Attributable risks associated with ASA discontinuation were calculated and National Institute for Health and Clinical Excellence annual economic data were used to estimate healthcare costs. The cumulative incidences of non-fatal MI/coronary death, IS/TIA and UGIB among ASA discontinuers within the first year of follow-up were 17, 11 and 1.6 per 1,000 persons, respectively. This corresponds to eight extra cardiovascular events, and a reduction of 0.4 UGIB events per year compared with current ASA users. Extrapolating to the UK population aged over 50 years, avoiding discontinuation of ASA could prevent 12,786 coronary and 7,672 cerebrovascular events/year, at the expense of 1023 extra UGIB events, saving approximately £100 million/year. In conclusion, preventing patients with cardiovascular disease from discontinuing ASA could result in substantial clinical and economic gains. © Schattauer 2013.


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.


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.


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.


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

Some pharmacokinetic studies have reported that proton pump inhibitors (PPIs) reduce the activity of clopidogrel, but the results of studies assessing clinical outcomes in patients receiving both drugs are inconsistent. We have therefore carried out a population-based cohort study with nested case-control analysis, in order to evaluate changes in the risk of cardiovascular and peptic ulcer bleeding (PUB) events associated with PPI use in patients receiving clopidogrel. A total of 42,542 patients aged 50-84 years in 2000-2007 who survived an acute coronary event were identified in two UK-based primary care databases (The Health Improvement Network and the General Practice Research Database). Individuals were followed up to identify incident cases of non-fatal myocardial infarction/coronary death (n = 2,546) and PUB (n = 194). Controls were frequency matched to cases by age, sex and calendar year. Compared with PPI non-use, current continuous PPI use was not associated with a significant change in risk of non-fatal myocardial infarction/coronary death among current continuous users of clopidogrel monotherapy (relative risk [RR], 1.06; 95% confidence interval [95% CI], 0.47 to 2.36) or dual antiplatelet therapy (DAT; RR, 0.80; 95% CI, 0.47 to 1.37) who initiated their antiplatelet therapy shortly after their coronary event. Among patients prescribed DAT at the start date, the RR of PUB events associated with current PPI use initiated at the start date was 0.66 (95% CI, 0.27 to 1.60). © Schattauer 2013.


Cea Soriano L.,Spanish Center for Pharmacoepidemiologic Research | Rothenbacher D.,University of Ulm | Choi H.K.,Boston University | Garcia Rodriguez L.A.,Spanish Center for Pharmacoepidemiologic Research
Arthritis Research and Therapy | Year: 2010

Introduction: The objective of this study was to investigate the contemporary incidence of gout, examine potential risk factors, and evaluate specific gout treatment patterns in the general population.Methods: Using the health improvement network (THIN) UK primary care database, we estimated the incidence of gout based on 24,768 newly diagnosed gout patients among a cohort of 1,775,505 individuals aged 20 to 89 years between 2000 and 2007. We evaluated potential risk factors for incident gout in a nested case-control study with 50,000 controls frequency-matched by age, sex and calendar time. We calculated odds ratios (OR) by means of unconditional logistic regression adjusting for demographic variables, lifestyle variables, relevant medical conditions and drug exposures.Results: The incidence of gout per 1,000 person-years was 2.68 (4.42 in men and 1.32 in women) and increased with age. Conventional risk factors were significantly and strongly associated with the risk of gout, with multivariate ORs of 3.00 (95% confidence interval (CI)) for excessive alcohol intake (that is, more than 42 units per week), 2.34 (95% CI 2.22 to 2.47) for obesity (body mass index > = 30 kg/m2), 2.48 (95% CI 2.19 to 2.81) for chronic renal impairment, and 3.00 (95% CI 2.85 to 3.15) for current diuretic use. For other medical conditions the multivariate OR were 1.84 (95% CI 1.70 to 2.00) for heart failure, 1.45 (95% CI 1.18 to 1.79) for hypertriglyceridemia and 1.12 (95% CI 1.04 to 1.22) for psoriasis. Use of cyclosporine was associated with an OR of 3.72 (95% CI, 2.17 to 6.40). Among gout-specific therapies, allopurinol was the most frequently used with a one-year cumulative incidence of 28% in a cohort of incident gout diagnosed from 2000 to 2001. Use of gout-specific treatment has not changed over recent years except for an increase of colchicine.Conclusions: The contemporary incidence of gout in UK remains substantial. In this general population cohort, associations with previously purported risk factors were evident including psoriasis, heart failure, hypertriglyceridemia, and cyclosporine therapy. Use of gout-specific treatment has remained relatively constant in recent years except for an increase of colchicine. © 2011 Cea Soriano et al.; licensee BioMed Central Ltd.


Michel A.,Bayer AG | Martin-Perez M.,Spanish Center for Pharmacoepidemiologic Research | Ruigomez A.,Spanish Center for Pharmacoepidemiologic Research | Garcia Rodriguez L.A.,Spanish Center for Pharmacoepidemiologic Research
European Journal of Heart Failure | Year: 2015

Aims: The aim of this study was to identify risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure in the UK. Methods and results: A nested case-control study was conducted using data from The Health Improvement Network primary care database. A cohort of 19 194 patients aged 1-89 years between January 2000 and December 2005 with newly diagnosed heart failure was followed up and cases of hyperkalaemia identified. Cases were frequency matched to controls by age, sex, and calendar year, and information on demographics, co-morbidities, co-medications, and lifestyle factors was extracted from the database. Using unconditional logistic regression models, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify potential risk factors. In total, 2176 hyperkalaemia cases were identified over a mean follow-up of 3.9years. Significant risk factors for hyperkalaemia were: renal failure (OR 3.81; 95% CI 3.29-4.42), type II diabetes (OR 1.52; 95% CI 1.31-1.75), valvular heart disease (OR 1.28; 95% CI 1.06-1.54), and current use of potassium-sparing diuretics (OR 3.01; 95% CI 2.61-3.48), ACE inhibitors (OR 1.70; 95% CI 1.41-2.04), trimethoprim (OR 2.82; 95% CI 1.88-4.23), non-steroidal anti-inflammatory drugs (OR 1.41; 95% CI 1.11-1.79), and several drug combinations. The risk was highest within the first month of medication use and decreased thereafter. Conclusion: Our findings may help to better identify patients with heart failure most likely to benefit from careful monitoring of serum potassium levels. Particular vigilance is needed during the start of treatment with certain medications. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.


Vassilev Z.P.,Bayer AG | Ruigomez A.,Spanish Center for Pharmacoepidemiologic Research | Soriano-Gabarro M.,Bayer AG | Rodrguez L.A.G.,Spanish Center for Pharmacoepidemiologic Research
Investigative Ophthalmology and Visual Science | Year: 2015

PURPOSE. Age-related macular degeneration (AMD) is the most common cause of legal blindness in Western patients over 65 years of age. We aimed to establish the incidence of AMD, and the association of diabetes, and cardiovascular and eye diseases with the risk of AMD, in a large cohort of primary care patients in the United Kingdom. METHODS. Using data from The Health Improvement Network database in the United Kingdom, all individuals with a first recorded diagnosis of AMD from 2004 to 2010 were identified (N ¼ 10,516) and frequency-matched to 19,389 AMD-free individuals by age, sex, and calendar year of AMD occurrence. Logistic regression was used to examine comorbidities and risk factors for AMD. RESULTS. The incidence of AMD was 18.08 (95% confidence interval [CI], 17.74-18.43) per 10,000 person-years. A positive association with AMD was observed for smoking, a high frequency of primary care visits, and referrals. Diabetes and use of antidiabetic drugs were associated with an increased risk of AMD. Prevalence of cardiovascular diseases among AMD patients was slightly higher than in controls, with a small increased risk of AMD among patients with myocardial infarction, heart failure, or hyperlipidemia. Positive associations were observed between prior eye diseases and risk of AMD, in particular for chorioretinal disorders. CONCLUSIONS. The incidence of AMD in the United Kingdom is in line with previously reported incidence rates from population-based studies. The study suggests an association between diabetes, prior eye diseases, cardiovascular comorbidities and AMD risk, and a link between AMD and higher healthcare utilization. © 2015 The Association for Research in Vision and Ophthalmology, Inc.

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