Luis Alberto Garcia-Rodriguez

The Centro Español de Investigación Farmacoepidemiológica · CEIFE

Importance Patients with atrial fibrillation (AF) can have an ischemic stroke (IS) despite oral anticoagulant (OAC) treatment. Knowledge regarding the association between OAC discontinuation and the subsequent risk of recurrent IS in patients with AF is limited. Objectives To determine the risk of recurrent IS in patients with AF receiving OAC and...

Background and objectives: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar...

Background The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. Methods Cohorts were created using electronic healthcare databases from the UK, the Netherlan...

Objectives To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements. Design PASS programme of rivar...

Background Survivors of spontaneous intracerebral hemorrhage (ICH) may have indications for statin therapy. The effect of statins on the risk of subsequent hemorrhagic and ischemic stroke (IS) in this setting is uncertain. We sought to determine the risk of any stroke (ischemic stroke, IS or recurrent-ICH), IS and recurrent-ICH associated with stat...

Importance: Survivors of spontaneous (ie, nontraumatic and with no known structural cause) intracerebral hemorrhage (ICH) have an increased risk of major cardiovascular events (MACEs), including recurrent ICH, ischemic stroke (IS), and myocardial infarction (MI). Only limited data are available from large, unselected population studies assessing t...

Background The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. Methods Cohorts were created using healthcare databases from the UK, the Netherlands, Germany...

Background: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. Research design and methods: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outc...

Introduction Large numbers of patients with type 2 diabetes receive treatment with a sodium-glucose co-transporter-2 inhibitor (SGLT2i). We investigated whether the cardiorenal preventative effects found in clinical trials are also seen in clinical practice where patient characteristics and adherence to treatment differ. Research design and method...

Background A causal relationship between statin use and intracerebral hemorrhage (ICH) is uncertain. We hypothesized that an association between long-term statin exposure and ICH risk might vary for different ICH locations. Methods We conducted this analysis using linked Danish nationwide registries. Within the Southern Denmark Region (population...

Importance Patients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population. Objective To evaluate the risk of a MACE for pa...

Aims A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. Methods A cost-utility analysis estimated the impact of n...

Background: Reducing stroke occurrence requires the effective management of cardiovascular and other stroke risk factors. Purpose: To describe pre- and post-stroke medication use, focusing on antithrombotic therapy and mortality risk, in individuals hospitalised for ischaemic stroke (IS) in the UK. Method: Using primary care electronic health...

Introduction As large numbers of patients with type 2 diabetes receive treatment with a sodium-glucose co-transporter-2 inhibitor (SGLT2i), we investigated whether the cardio-renal preventative effects found in clinical trials are also seen in clinical practice where patient characteristics and adherence to treatment differs. Research design and m...

Objectives To investigate effects of appropriately and inappropriately dosed apixaban/rivaroxaban versus warfarin on effectiveness and safety outcomes in patients with non-valvular atrial fibrillation (NVAF). Design Cohort study with nested case–control analyses using primary care electronic health records (IQVIA Medical Research Data UK database)...

Background and objectives: A causal relationship between long-term statin use and the risk of intracerebral hemorrhage (ICH) remains uncertain. We investigated the association between statin use prior to hospital admission for ICH in a Danish population-based, nationwide case-control study. Methods: We used the Danish Stroke Registry to identify...

Acute kidney injury (AKI) has been associated with use of oral anticoagulants (OACs) in patients with non-valvular atrial fibrillation (NVAF). We aimed to compare AKI risk among users of rivaroxaban vs. warfarin. We identified two cohorts of NVAF patients who initiated rivaroxaban (15/20 mg/day, N=6436) or warfarin (N=7129) excluding those without...

(1) Background: The pleiotropic effects of statins may explain a chemoprotective action against colorectal cancer (CRC). Many studies have tested this hypothesis, but results have been inconsistent so far. Moreover, few have examined statins individually which is important for determining whether there is a class effect and if lipophilicity and int...

Purpose To evaluate time trends in the prevalence of antithrombotic and statin use in four European countries. Methods Using population-based data from the United Kingdom, Denmark, Spain and Italy between 2010 and 2018, we calculated standardized annual prevalence proportions of antithrombotics and statin use, and changes in prevalence proportions...

Background Reports suggest that renal decline is greater among patients with non-valvular atrial fibrillation (NVAF) treated chronically with warfarin vs. some non-vitamin K antagonist oral anticoagulants. Methods and results Using primary care electronic health records from the United Kingdom we followed adults with NVAF and who started rivaroxab...

Purpose To compare the risk of acute kidney injury (AKI) among users of rivaroxaban vs warfarin. Patients and Methods We identified two cohorts of patients with non-valvular atrial fibrillation (NVAF) who initiated rivaroxaban (15/20 mg/day, N = 6436) or warfarin (N = 7129) excluding those without estimated glomerular filtration rate values record...

Background A recent observational study (1) has suggested that renal decline among patients with non-valvular atrial fibrillation (NVAF) could be faster in users of warfarin vs. rivaroxaban. Purpose To estimate renal decline in patients with NVAF and preserved renal function who started oral anticoagulant (OAC) therapy with rivaroxaban 20 mg or wa...

Background Low-dose aspirin therapy reduces the risk of cardiovascular disease and may have a positive effect on the prevention of colorectal cancer. We evaluated the population-level expected effect of regular low-dose aspirin use on cardiovascular disease (CVD), colorectal cancer (CRC), gastrointestinal bleeding, symptomatic peptic ulcers, and in...

Introduction We aimed to determine the incidence of, and risk factors for all-cause/cardiovascular disease (CVD) mortality, and end-stage renal disease (ESRD) among people with type 2 diabetes with/without diabetic kidney disease (DKD) in the UK general population. Research design and methods We undertook a population-based cohort study using prim...

Importance: Spontaneous (nontraumatic) intracerebral hemorrhage (ICH) is the most severe complication of antithrombotic drug use. Objectives: To estimate the strength of association between use of antithrombotic drugs and risk of ICH and to examine major changes in the incidence of ICH in the general population. Design, setting, and participant...

Introduction: Classification of intracranial bleeding (ICB) by trauma status is important in research relating to anticoagulant therapy. We evaluated trauma status of ICB subtypes - intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) - in a large population of patients with non-valvular atrial fibrillation (NVA...

IntroductionA multinational post-authorization safety study assessed cardiovascular safety in initiators of prucalopride for chronic constipation compared with a matched cohort of polyethylene glycol 3350 initiators. The primary safety outcome was major adverse cardiovascular events (MACE), a composite of hospitalization for acute myocardial infarc...

Objective To evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF). Methods We undertook a population-based cohort study with nested case–control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked regist...

Purpose To establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). Patients and Methods Based on discharge summaries and brain imaging reports, we estimated the positive predictive value (PPV) of a first-ever diagnosis code for ICH (ICD-10, code I61) fo...

Background Regular use of low-dose aspirin (LDA) has been shown to reduce the risk of cardiovascular disease (CVD). Recent evidence indicates that regular LDA use also reduces the risk of colorectal cancer (CRC). Use of LDA has also been associated with an increased risk of gastrointestinal (GI) bleeding, peptic ulcers and intracranial hemorrhage (...

Purpose We aimed to describe time‐trends in the use of NOACs among a group of ambulatory patients with nonvalvular atrial fibrillation (NVAF) in Colombia and to describe treatment patterns and user characteristics. Methods Using the Audifarma S.A administrative healthcare database in Colombia, we identified 10 528 patients with NVAF aged at least...

Purpose: To describe the effect that validation of venous thromboembolism (VTE) coded entries in the health improvement network (THIN) has on incidence rates of VTE among a cohort of rivaroxaban/warfarin users. Methods: Among 36 701 individuals with a first prescription for rivaroxaban/warfarin between 2012 and 2015, we performed a two-step VTE...

Background Rivaroxaban is a highly selective factor Xa inhibitor approved for use in Europe for multiple indications. Study design and methods The European rivaroxaban epidemiological post-authorization safety study (PASS) program consists of seven complementary observational studies. For four of the studies, data are obtained from healthcare data...

Background: Worldwide the rate of unplanned pregnancies is more than 40%. Identifying women at risk of pregnancy can help prevent negative outcomes and also reduce healthcare costs of potential complications. It can also allow the investigation of the natural history of pregnancy outcomes, such as ectopic pregnancies or miscarriages. The use of me...

Background Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical...

Randomized controlled trials (RCTs) have strong internal validity but often have limited external validity. Observational studies have good generalizability and an increasing role in key healthcare decision making. We compared incidence rates of intracranial and major gastrointestinal bleeds in the low-dose aspirin arm (N = 9126) of the COMPASS dou...

There is increasing interest regarding potential protective effects of low‐dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low‐dose aspirin and risk of gastric/oesophageal cancer using a population‐based primary care database in the UK. Between January 2005 and December 2015, we identified...

Objectives To study the effect of risk minimization measures taken in 2013 for cyproterone acetate/ethinylestradiol (CPA/EE) on initiation, concomitant use of other hormonal contraceptives (HC) and potential indications. Study design This retrospective study included data on CPA/EE use in 2011-2017 from the Netherlands, UK, and Italy. Results The...

Purpose There is an increase interest on the potential chemoprotective effect of selective phosphodiesterase 5 (PDE5) inhibitors. Several authors have shown in vivo the immune‐mediated anti‐tumor effect of these inhibitors on tumors arising from the digestive tract. Objectives To test the potential effect of selective PDE5 inhibitors against color...

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049...

Background: Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in rou...

Objectives: To test the hypothesis that allopurinol reduces the risk of acute myocardial infarction (AMI) in hyperuricemic patients and to assess whether the effect is dependent on dose, duration and serum uric acid (SUA) level attained after treatment. Methods: Nested case-control study over the period 2002-2015. From a cohort of patients aged...

Aim: To estimate the incidence and risk factors of chronic kidney disease (CKD) in patients with newly-diagnosed diabetes using different CKD definitions. Methods: Using UK primary care data, patients with diabetes (type 1, 4691; type 2, 109,365) and no CKD were followed to identify newly-diagnosed CKD, classified by a broad and narrow CKD defin...

Background Evidence suggests that low-dose aspirin is associated with a 30–40% protective effect against colorectal cancer (CRC) yet its effect on other gastrointestinal cancers has been less studied. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/ oesophageal cancer using a population-based primary care da...

Background: Selective serotonin reuptake inhibitors (SSRIs) use may be associated with development of subdural hematoma (SDH). Objectives: To estimate SDH risk associated with antidepressant use, including when combined with antithrombotics, or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients/methods: We performed this case-control stud...

Objective To determine discontinuation rates, patterns of use and predictors of discontinuation of non-vitamin K antagonist oral anticoagulants (NOACs) among patients with non-valvular atrial fibrillation (NVAF) in the first year of therapy. Design Population-based cohort study. Setting UK primary care. Population 11 481 patients with NVAF and a...

Background Despite widespread use of non-vitamin K antagonist oral anticoagulants (NOACs), real-world data on time to discontinuation and time to re-initiation of the NOAC treatment are still scarce. Purpose To identify patterns of time to discontinuation as well as time to re-initiation of NOACs in patients with NVAF during the first year of trea...

Background Current labelling for NOACs considers dose adjustments based on renal function and for some also patients' age, weight, comorbidities, and concomitant treatments. There is limited data on factors associated with inappropriately underdosing of NOACs according to the label in routine care. Purpose To assess factors associated with inappro...

Objective To evaluate the appropriateness of the initial prescribed daily dose of non-vitamin K antagonist oral anticoagulants (NOACs) according to label in patients with non-valvular atrial fibrillation (NVAF) in the UK. Design Population-based cross-sectional study. Setting UK primary care. Population 30 467 patients with NVAF and a first pres...

Background Meta-analysis of trial data suggests that in primary cardiovascular disease (CVD) prevention bodyweight modifies low-dose aspirin's effects on colorectal cancer (CRC) and major bleeding risk. We sought to investigate whether these effects are seen in patients with or without CVD in routine clinical practice by undertaking sub-analyses of...

Background: Inflammation and overexpression of cyclooxygenase-2 (COX-2) have been described to play a key role in the progression from nonpathologic intestinal mucosa to colorectal cancer (CRC). Aims: To assess the chemoprotective effect of non-aspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) under different patterns of use in a Mediterr...

Objectives Hypotension is of particular relevance for patients with heart failure (HF), since almost all HF drugs cause lowering of blood pressure (BP) and it is associated with a poor prognosis. We aimed to investigate hypotension incidence and risk factors in patients with incident HF in the UK. Design Retrospective cohort study including nested...

Introduction The serotonin 5-HT4 receptor agonist prucalopride is approved in the European Union for the treatment of chronic constipation. This offered the unique opportunity to include real-world observational data on cardiovascular safety in the new drug application for approval of prucalopride in the USA. Methods This observational population-...

Introduction Given prior safety experience with other 5-HT4 agonists for chronic constipation, an observational, population-based cohort study in five data sources from Germany, Sweden, and the UK was conducted to evaluate the cardiovascular safety of prucalopride. Objectives Our objective is to describe the methods and resulting comparability of...

Introduction/objectives To compare the risk of different bleeding outcomes between patients with systemic sclerosis (SSc) and the general population free of SSc. Methods Using UK electronic primary care data (2000–2012), 1314 patients with SSc and a matched SSc-free comparison cohort (n = 19,992) were followed until December 2013 to identify bleed...

Introduction: Risks of low-dose aspirin-associated upper and lower gastrointestinal bleeds (UGIB/LGIB) may vary by severity and presence of cardiovascular disease (CVD). No study has quantified these risks for UGIB and LGIB in the same real-world study population. Patients and methods: Using UK primary care data, 199,049 new users of low-dose aspir...

Background Epidemiological research on small cell lung cancer (SCLC) is limited and based on cancer registry data. We evaluated the feasibility and validity of using primary care electronic health records (The Health Improvement Network [THIN]) in the UK to identify and characterise SCLC. Methods We searched THIN records of individuals aged 18–89...

Background Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes. Objective This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of...

Purpose To define and validate a case‐finding algorithm to identify incident colorectal cancer (CRC) in the Spanish primary care database BIFAP. Methods All potential incident CRC cases recorded during the study period 2001 to 2014 among patients 20 to 89 years old were identified using a defined case‐finding algorithm tailored to BIFAP database c...

Objective: To estimate the contemporary epidemiology of systemic sclerosis (SSc) in the UK and to explore the validity of using The Health Improvement Network (THIN) primary care database to study SSc. Methods: 4,520,299 individuals (2000-2012) aged 1-99 years were followed to identify potential incident cases of SSc; potential prevalent cases w...

Purpose: Endogenous human gonadal steroids and especially female sex hormones modulate the risk of developing epileptic seizures. In most circumstances, estrogens increase excitability, while progesterone bears substantial anticonvulsive properties. We questioned whether exogenous gonadal steroids used as hormonal contraception are associated with...

Purpose The purpose of this study is to establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). Patients and methods We estimated the positive predictive value (PPV) of ICH diagnoses for a sample of 500 patients from the DSR (patients recorded under ICH...

Background: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. Objectives: This study sought to determine the association between initiation of SGLT-...

Background & aims: There are few data on the incidence of upper and lower gastrointestinal bleeding (UGIB and LGIB) from observational studies of low-dose aspirin users. We aimed to estimate incidence rates of UGIB and LGIB in a large cohort of new users of low-dose aspirin in the United Kingdom, with sub-analyses of hospitalization status and fat...

Purpose The purpose of the study is to evaluate the impact of validation on the identification of major bleeding events in The Health Improvement Network (THIN) database in patients receiving anticoagulant therapy. Methods Patients aged 2 to 89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin) between 2012 and 2015 wer...

Purpose To evaluate misclassification of intracranial bleeding (ICB) onset in The Health Improvement Network and assess its impact on risk associated with low‐dose aspirin preventive therapy. Methods A total of 199 049 new users of low‐dose aspirin and 1:1 matched non‐users were followed to identify incident ICB cases with validation involving man...

Purpose Our goal was to describe the management of pregestational diabetes in pregnant women in the United Kingdom. Methods We used electronic medical records from The Health Improvement Network database between January 1995 and June 2012 to identify the first pregnancy in women 15 to 45 years of age with pregestational diabetes type 1 or type 2....