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.
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.
49,170 cases of IS were observed among 4,593,778 new NSAID users. Use of coxibs (odds ratio 1.08, 95%-confidence interval 1.02-1.15) and use of traditional NSAIDs (1.16, 1.12-1.19) were associated with an increased risk of IS. Among 32 individual NSAIDs evaluated, the highest significant risk of IS was observed for ketorolac (1.46, 1.19-1.78), but significantly increased risks (in decreasing order) were also found for diclofenac, indomethacin, rofecoxib, ibuprofen, nimesulide, diclofenac with misoprostol, and piroxicam. IS risk associated with NSAID use was generally higher in persons of younger age, males, and those with a prior history of IS.
Risk of IS differs between individual NSAIDs and appears to be higher in patients with a prior history of IS or transient ischemic attack (TIA), in younger or male patients. Co-medication with aspirin, other antiplatelets or anticoagulants might mitigate this risk. The small to moderate observed risk increase (by 13-46%) associated with NSAIDs use represents a public health concern due to widespread NSAID usage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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).
Methods
First, we identified AMI, stroke, smoking, obesity, and menopausal status in a cohort treated for overactive bladder by applying computerized algorithms to primary care medical records (2004–2012). We validated these cardiovascular outcomes and risk factors with physician questionnaires (gold standard for this analysis). Second, we estimated IRRs for AMI and stroke using algorithm–identified and questionnaire–confirmed cases, comparing these with IRRs from cases identified through linkage with hospitalization/mortality data (best estimate).
Results
For AMI, the algorithm's positive predictive value (PPV) was >90%. Initial algorithms for stroke performed less well because of inclusion of codes for prevalent stroke; algorithm refinement increased PPV to 80% but decreased sensitivity by 20%. Algorithms for smoking and obesity were considered valid. IRRs based on questionnaire‐confirmed cases only were closer to IRRs estimated from hospitalization/mortality data than IRRs from algorithm‐identified cases.
Conclusions
AMI, stroke, smoking, obesity, and postmenopausal status can be accurately identified in CPRD. Physician questionnaire–validated AMI and stroke cases yield IRRs closest to the best estimate.
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.
Outcome Measurements and Main Results
Using tolterodine as the reference, we estimated propensity‐score–stratified incidence rate ratios (IRRs) for acute myocardial infarction, stroke, CV mortality, major adverse cardiac events (MACE, a combined end point of the previous three), and all‐cause death for individual antimuscarinic drugs. The study cohort included 119,912 new users of OAB drugs. The mean age at cohort entry was 62 years, 70% were female, and the mean follow‐up was 3.3 years. The adjusted IRR for MACE and current use of oxybutynin compared with current use of tolterodine was 1.14 (95% confidence interval CI 1.01–1.30). In contrast, the IRR was 0.65 (CI 0.56–0.76) for current use of solifenacin compared with tolterodine. In this study, performed with health care data, the distribution of risk factors was relatively similar across users of different OAB drugs and, although our analyses controlled for a range of measured potential confounders, residual confounding cannot be ruled out.
Conclusions
In an observational comparative study of users of medications to treat OAB conducted in routine clinical practice, the risk for CV side effects was increased in users of oxybutynin and decreased in users of solifenacin compared with users of tolterodine.
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.
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. For each question in the RTI-IB (n=31), the observed interrater agreement was calculated as the percentage of studies given the same bias assessment by both reviewers; chance-adjusted interrater agreement was estimated with the first-order agreement coefficient (AC1) statistic.
The NOS required less tailoring and was easier to use than the RTI-IB, but the RTI-IB produced a more thorough assessment. The RTI-IB includes most of the domains measured in the NOS. Median observed interrater agreement for the RTI-IB was 75% (25th percentile p25 =61%; p75 =89%); median AC1 statistic was 0.64 (p25 =0.51; p75 =0.86).
The RTI-IB facilitates a more complete quality assessment than the NOS but is more burdensome. The observed agreement and AC1 statistic in this study were higher than those reported by the RTI-IB's developers.
: 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. Sixteen original studies were selected according to predefined criteria. Two researchers independently extracted the data on individual study characteristics and results. The authors calculated pooled relative risk (RR) estimates of myocardial infarction for specific NSAIDs compared with no NSAID use, tested the heterogeneity of effects, and evaluated potential reasons for heterogeneity. The pooled RR of myocardial infarction was 0.98 (95% confidence interval (CI): 0.92–1.05) for naproxen, 1.07 (95% CI: 1.02–1.12) for ibuprofen, 1.44 (95% CI: 1.32–1.56) for diclofenac, 0.96 (95% CI: 0.90–1.02) for celecoxib, and 1.26 (95% CI: 1.17–1.36) for rofecoxib (all doses). The pooled RR for rofecoxib at doses >25 mg/day was 1.78 (95% CI: 1.36–2.34), and 1.18 (95% CI: 1.07–1.31) for doses ≤25 mg/day. The RR associated with naproxen was 0.83 (95% CI: 0.72–0.90) among non‐users of low‐dose aspirin. The RR associated with rofecoxib (all doses) was 1.39 (95% CI: 1.25–1.54) among subjects without a history of myocardial infarction. The risk of myocardial infarction varies with individual NSAIDs. An increased risk was observed for diclofenac and rofecoxib, the latter one with a clear dose‐response trend. There was a suggestion of a small increased risk with ibuprofen. Also, data suggest a small reduced risk for naproxen present only in non‐users of aspirin, mainly people free of clinically apparent vascular disease.
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. Two definitions were used to estimate potential off‐label use: a broad definition of on‐label prescribing using codes for disease indication (eg, atrial fibrillation AF), and a restrictive definition excluding patients with conditions for which dabigatran is not indicated (eg, valvular AF).
Results
Prevalence estimates under the broad definition ranged from 5.7% (CPRD‐HES) to 34.0% (CSD‐LPD) and, under the restrictive definition, from 17.4% (CPRD‐HES) to 44.1% (CSD‐LPD). For the majority of potential off‐label users, no diagnosis potentially related to anticoagulant use was identified. Key methodological challenges were the limited availability of detailed clinical information, likely leading to overestimation of off‐label use, and differences in the information available, which may explain the disparate prevalence estimates across data sources.
Conclusions
Estimates of potential off‐label use should be interpreted cautiously due to limitations in available information. In this context, CPRD HES‐linkable estimates are likely to be the most accurate.
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