Validation of cardiovascular outcomes and risk factors in the Clinical Practice Research Datalink in the United Kingdom.

Purpose: Strategies to identify and validate acute myocardial infarction (AMI) and stroke in primary-care electronic records may impact effect measures, but to an unknown extent. Additionally, the validity of cardiovascular risk factors that could act as confounders in studies on those endpoints has not been thoroughly assessed in the United Kingdom Clinical Practice Research Datalink's (CPRD's) GOLD database. We explored the validity of algorithms to identify cardiovascular outcomes and risk factors and evaluated different outcome-identification strategies using these algorithms for estimation of adjusted incidence rate ratios (IRRs).

Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project.

Background: Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used.

Objectives: To estimate the risk of AMI for individual NSAIDs.

Risk of ischemic stroke and the use of individual non-steroidal anti-inflammatory drugs: A multi-country European database study within the SOS Project.

Background And Purpose: A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication.

Methods: Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated.

Variation in Cardiovascular Risk Related to Individual Antimuscarinic Drugs Used to Treat Overactive Bladder: A UK Cohort Study.

Background: Blocking muscarinic receptors could have an effect on cardiac function, especially among elderly patients with overactive bladder (OAB).

Study Objective: To investigate the risk of cardiovascular (CV) events in users of antimuscarinic drugs to treat OAB.

Design, Setting, And Participants: Cohort study of new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium, 18 years or older, in the United Kingdom's Clinical Practice Research Datalink (CPRD), 2004-2012.

Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe.

Purpose: To report and discuss estimated prevalence of potential off-label use and associated methodological challenges using a case study of dabigatran.

Methods: Observational, cross-sectional study using 3 databases with different types of clinical information available: Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD), France (cardiologist panel, n = 1706; general practitioner panel, n = 2813; primary care data); National Health Databases, Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus hospital data for HES-linkable patients).

Study Period: August 2011 to August 2015.

Comparison of cardiovascular events among treatments for overactive bladder: a Danish nationwide cohort study.

Purpose: The purpose of this study is to explore the cardiovascular safety of antimuscarinic drugs to treat overactive bladder (OAB) in Denmark.

Methods: This was a cohort study using data recorded in Danish registries from patients newly exposed to darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium in 2004-2012. We estimated crude and standardized incidence rates (IRs) for acute myocardial infarction (AMI); stroke; cardiovascular mortality; major adverse cardiac events (MACE, a combined endpoint of the previous three outcomes); and all-cause death for the individual and combined drugs.

Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany.

Purpose: To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency.

Methods: New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing.

Improving the Identification of Out-of-Hospital Sudden Cardiac Deaths in a General Practice Research Database.

Background: The ascertainment of sudden cardiac death (SCD) in electronic health databases is challenging.

Objectives: Our objective was to evaluate the applicability of the validated computer definition of SCD developed by Chung et al. in a retrospective study of SCD and domperidone exposure in the Clinical Practice Research Datalink (CPRD).

Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study.

Objectives: To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs.

Design: Nested case-control study.

Setting: Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom).

Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies.

Background: The results of observational studies evaluating and comparing the cardiovascular safety of glitazones, metformin and sufonylureas are inconsistent.To conduct and evaluate heterogeneity in a meta-analysis of observational studies on the risk of acute myocardial infarction (AMI) or stroke in patients with type 2 diabetes using non-insulin blood glucose-lowering drugs (NIBGLD).

Methods: We systematically identified and reviewed studies evaluating NIBGLD in patients with type 2 diabetes indexed in Medline, Embase, or the Cochrane Library that met prespecified criteria.

Risk of Out-of-Hospital Sudden Cardiac Death in Users of Domperidone, Proton Pump Inhibitors, or Metoclopramide: A Population-Based Nested Case-Control Study.

Introduction: Epidemiological studies have linked domperidone use with serious cardiac arrhythmias, including sudden cardiac death, but data on age, dose, and duration of use are limited.

Objectives: The aim of this study was to assess the risk of out-of-hospital sudden cardiac death associated with domperidone use versus proton pump inhibitors (PPIs), metoclopramide, or non-use of all three medications, and to evaluate the risk of sudden cardiac death in relation to age and domperidone dose.

Methods: This was a population-based case-control study nested in a cohort of subjects aged ≥2 years in the Clinical Practice Research Datalink with one or more prescriptions for domperidone, any PPI, or metoclopramide from 2005 to 2011.

Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa Scale and the RTI item bank.

Background: The study objective was to compare the Newcastle-Ottawa Scale (NOS) and the RTI item bank (RTI-IB) and estimate interrater agreement using the RTI-IB within a systematic review on the cardiovascular safety of glucose-lowering drugs.

Methods: We tailored both tools and added four questions to the RTI-IB. Two reviewers assessed the quality of the 44 included studies with both tools, (independently for the RTI-IB) and agreed on which responses conveyed low, unclear, or high risk of bias.

The risk of heart failure associated with the use of noninsulin blood glucose-lowering drugs: systematic review and meta-analysis of published observational studies.

Background: Patients with type 2 diabetes mellitus (T2DM) are at high risk of heart failure. A summary of the effects of blood glucose-lowering drugs other than glitazones on the risk of heart failure in routine clinical practice is lacking. The objective of this study was to conduct a systematic review and meta-analysis of observational studies on the risk of heart failure when using blood glucose-lowering drugs.

Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysis of observational studies.

Objective: To conduct a systematic review of observational studies on the risk of acute myocardial infarction (AMI) with use of individual nonsteroidal anti-inflammatory drugs (NSAIDs).

Methods: A search of Medline (PubMed) for observational studies published from 1990 to 2011 identified 3829 articles; 31 reported relative risk (RR) of AMI with use of individual NSAIDs versus nonuse of NSAIDs. Information abstracted in a standardized form from 25 publications was used for the meta-analysis on 18 independent study populations.

Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project).

Background: The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs; however, there is little information on the risk associated with some NSAIDs and on the impact of risk factors. These data are necessary to evaluate the benefit-risk of individual NSAIDs for clinical and health policy decision making.

Stroke risk and NSAIDs: a systematic review of observational studies.

Aims: To perform a quantitative systematic review of observational studies on the risk of stroke associated with the use of individual NSAIDs.

Methods And Results: Searches were conducted using the Medline database within PubMed (1990-2008). Observational cohort or case-control studies were eligible if reported on the risk of cardiovascular events associated with individual NSAIDs versus the nonuse of NSAIDs.

Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study.

Purpose: Limited information from spontaneous reports and results of two case-control studies raised concern about the cardiotoxicity of oral domperidone therapy. This case-control study nested in a retrospective cohort evaluated the combined risk of serious ventricular arrhythmia (SVA) and sudden cardiac death (SCD) in users of domperidone compared with users of proton pump inhibitors (PPIs), or non-users of these medications.

Methods: A cohort of users of domperidone or a PPI from 1990 to 2005 was identified from existing electronic databases of Saskatchewan Health.

Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease.

Background: The cardiovascular safety of individual nonsteroidal antiinflammatory drugs (NSAIDs) is highly controversial, particularly in persons with serious coronary heart disease.

Methods And Results: We conducted a multisite retrospective cohort study of commonly used individual NSAIDs in Tennessee Medicaid, Saskatchewan Health, and United Kingdom General Practice Research databases. The cohort included 48566 patients recently hospitalized for myocardial infarction, revascularization, or unstable angina pectoris with more than 111000 person-years of follow-up.

The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada.

Background: Meta-analyses of observational studies show variability in the risk of acute myocardial infarction (AMI) among non-steroidal anti-inflammatory drugs (NSAIDs), with an increase in risk for rofecoxib and diclofenac, and no increase in risk for celecoxib, naproxen, or ibuprofen.

Methods And Results: We identified a cohort of 364 658 individuals aged 40-84 years who were enrolled in Saskatchewan Health, Canada, from 15 November 1999 to 31 December 2001. A nested case-control analysis compared 3252 incident cases of hospitalized AMI and out-of-hospital CHD deaths with 20 002 controls randomly sampled from the cohort.

Positive predictive value of ICD-9 codes 410 and 411 in the identification of cases of acute coronary syndromes in the Saskatchewan Hospital automated database.

Background: Case definitions are essential to epidemiological research.

Objectives: To evaluate ICD-9 codes 410 and 411 to identify cases of acute coronary syndromes (ACS), and the clinical information availability in the administrative and hospital discharge records of Saskatchewan, Canada.

Methods: In the context of a safety cohort study, we identified hospitalisations with primary discharge codes 410 (2260) and 411 (799).

Validation of ICD-9 codes with a high positive predictive value for incident strokes resulting in hospitalization using Medicaid health data.

Purpose: To validate ICD 9 codes with a high positive predictive value (PPV) for incident strokes. The study population consisted of Tennessee Medicaid enrollees aged from 50 to 84 years.

Methods: We identified all patients who were hospitalized with a discharge diagnosis of stroke between 1999 and 2003 using highly specific codes (ischemic stroke ICD 9-CM codes 433.

Quantitative assessment of the gastrointestinal and cardiovascular risk-benefit of celecoxib compared to individual NSAIDs at the population level.

Purpose: To estimate the net cardiovascular (CV) (coronary heart disease, stroke, congestive heart failure), and gastrointestinal (GI) (peptic ulcer complications) risk-benefit public health impact of the use of celecoxib compared to non-selective NSAIDs in the arthritis population.

Methods: We applied discrete event simulation models to data from the US National Health Surveys, CV risk-prediction models from the Framingham Heart Study, and population-based studies. Models took into account the multifactorial effect of risk factors, comorbidity, and competing risk of mortality.

Use of oral corticosteroids and the risk of acute myocardial infarction.

Introduction: A few epidemiological studies suggested an increased coronary heart disease (CHD) risk with high doses of oral corticosteroids.

Methods: We performed a cohort study with nested case-control analysis to estimate the risk of acute myocardial infarction (AMI) associated with the use of oral corticosteroids by dose and duration. We followed-up 404,183 persons, 50-84 years old, without cancer from the general UK population.

Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction.

Whether non-aspirin non-steroidal antiinflammatory drugs (NSAIDs) affect the risk of myocardial infarction is unclear. Also, it is unknown whether the effect varies by individual NSAIDs. To summarize the evidence from published observational studies on the risk of myocardial infarction associated with both traditional NSAIDs (tNSAIDs) and selective inhibitors of cyclooxygenase-2 (Coxibs), the authors conducted a systematic review of cohort and case-control studies on NSAIDs and myocardial infarction published between 2000 and 2005.