Tjeerd van Staa

Chronic atrial fibrillation: Incidence, prevalence, and prediction of stroke using the Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack (CHADS2) risk stratification scheme

BACKGROUND The aim of the study is to estimate the incidence and prevalence of chronic AF (cAF) in the United Kingdom and test the accuracy of the CHADS2 score for stroke prediction. METHODS The General Practice Research Database was used to identify patients aged 40+ years diagnosed with cAF and control patients. Harrells C-statistic was used to test possible improvements in CHADS2. RESULTS The study population included 51,807 cAF patients. The incidence of cAF increased by age and was higher in men than women. The prevalence of cAF has increased over time. The excess 5-year risk for stroke in cAF patients correlated well with CHADS2 as follows: score 0, 1.9% (95% CI 1.6-2.1); 1, 3.0% (95% CI 2.7-3.3); 2, 4.7% (95% CI 4.3-5.1); 3, 7.2% (95% CI 6.6-7.9); 4, 10.5% (95% CI 9.4-11.5); 5, 13.9% (95% CI 12.2-15.5); and 6, 15.8% (95% CI 13.5-18.1). Adding sex, the extension of age categories and reweighing of established risk factors improved CHADS2 accuracy (C-statistic 0.68-0.72). Applying the reclassification resulted in a substantial number of patients changing stroke risk category. CONCLUSION Atrial fibrillation is a prevalent and growing problem, which significantly increases the risk of ischemic stroke. The CHADS2 score is a good predictor of the stroke risk but could be improved.

Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database.

Summary:  Purpose: To compare the incidence of various fractures in a cohort of patients with epilepsy with a reference cohort of patients not having epilepsy.

Fracture outcomes related to persistence and compliance with oral bisphosphonates.

The effects of low persistence on fracture risk have not been fully addressed. The objectives of this study were to describe the persistence and compliance with bisphosphonates and to evaluate the association with fracture risk. The General Practice Research database was used to identify patients ≥18 yr of age prescribed alendronate or risedronate. The follow‐up was divided into periods of current and past use. Time‐dependent Cox regression was used. The study population included 44,531 patients; 58.3% of the patients continued bisphosphonate treatment for >1 yr and 23.6% for >5 yr. The risk of hip/femur fracture (adjusted relative rate [RR], 0.78; 95% CI, 0.64–0.94) and osteoporotic fracture (RR, 0.85; 95% CI, 0.76–0.94) were lower with current compared with past bisphosphonate use. The largest reduction in hip/femur and osteoporotic fracture risk was observed in patients treated for at least 6 mo and no reduction in those treated for <6 mo. The risks of hip/femur and osteoporotic fractures followed the pattern of nonosteoporotic fractures in the first 6 mo but then started to reduce after 6–12 mo of treatment. Increased risks of osteoporotic and hip/femur fractures were found in patients with low compliance. Use of bisphosphonates was associated with fracture risk reductions after 6–12 mo of treatment, but only 58% of the patients were treated for at least 1 year. Improvement in long‐term persistence to bisphosphonate treatment may be important to reduce the impact of osteoporosis‐related fractures.

Update on the epidemiology of Paget's disease of bone.

Pagets disease of bone (PDB) is characterized by rapid bone remodeling and the formation of bone that is structurally abnormal. Recent studies have confirmed that both genetic and environmental factors are important in its etiology. Epidemiological studies in Europe and North America have revealed that PDB shows an increasing frequency of occurrence with age and is more prevalent among men than women. There is marked geographic variation in the prevalence of PDB throughout western nations, with the highest rates reported during the 1970s in Britain. Recent studies of the secular trends in PDB suggest declining rates in both prevalence and severity at diagnosis. Thus, the overall age/sex standardized prevalence rate in Britain during the period 1993–1995 was found to be 2.5% among men and 1.6% among women ≥55 years of age. Prevalence rates had fallen by ∼50% in several of the centers studied, suggesting an environmental contribution to the etiology of this disorder. Similar findings have been reported from other European countries and New Zealand. Recent study of the incidence and clinical manifestations of PDB have emerged from large cohort studies in primary care record linkage resources, such as the General Practice Research Database. Over the period 1988–1999, the incidence rate of clinically diagnosed PDB was found to be 5 per 10,000 person‐years among men and 3 per 10,000 person‐years among women 75 years of age. The disorder was associated with an increased risk of back pain (RR, 2.1; 95% CI, 1.9–2.3); osteoarthritis (RR, 1.7; 95% CI, 1.5–1.9); and fracture (RR, 1.2; 95% CI, 1.0–1.5). Using life table methodology, the estimated proportion of patients dying within 5 years of follow‐up was 32.7% among the cohort with PDB compared with 28.0% among control patients (p < 0.05).

Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures

AIM Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and the risk of both osteoporotic and non-osteoporotic fractures. METHODS A case-control study was conducted using the PHARMO RLS. Cases were patients with a first hospital admission for a fracture during the study period. Up to four controls were matched to each case on gender, age, geographical area, and index date. RESULTS We identified 16,717 cases, of whom 59.5% had an osteoporotic fracture, and 61,517 controls. Compared to no use, current use of SSRIs was associated with a statistically significant increased risk of osteoporotic fractures (OR 1.95, 95% CI 1.69-2.26), as was current use of TCAs and non-SSRI/non-TCA antidepressant drugs (ORs 1.37, 95% CI 1.16-1.63 and 1.40, 95% CI 1.06-1.85, respectively). The risk of an osteoporotic fracture was statistically significantly higher for antidepressants with a high affinity for the 5-HTT (OR 1.86, 95% CI 1.63-2.13) compared to antidepressants with a medium or low affinity (OR 1.43, 95% CI 1.19-1.72 (medium) and OR 1.32 95% CI 0.98-1.79 (low) (p<0.05 for trend). The risk of non-osteoporotic fractures did not show the same trend. CONCLUSIONS The extent of affinity for the 5-HTT may contribute to the increased risk of osteoporotic fractures related to antidepressant drug use. The pharmacological mechanism-based classification could to be an appropriate alternative for traditional classification to study the association between the use of antidepressants and the risk of fractures.

Selective decrease in consultations and antibiotic prescribing for acute respiratory tract infections in UK primary care up to 2006.

Background The aim of this study was to estimate trends in primary care consultations and antibiotic prescribing for acute respiratory tract infections (RTIs) in the UK from 1997 to 2006. Methods Data were analysed for 100 000 subjects registered with 78 family practices in the UK General Practice Research Database; the numbers of consultations for RTI and associated antibiotic prescriptions were enumerated. Results The consultation rate for RTI declined in females from 442.2 per 1000 registered patients in 1997 to 330.9 in 2006, and in males from 318.5 to 249.0. The rate of consultations for colds, rhinitis and upper respiratory tract infection (URTI) declined by 4.2 (95% CI 2.3–6.1) per 1000 per year in females and by 3.6 (2.3–4.8) in males. The rate of antibiotic prescribing for RTI was higher in females and declined by 8.5 (2.0–15.1) per 1000 in females and 6.7 (2.7–10.8) in males. For colds, rhinitis and URTI, the proportion of consultations with antibiotics was prescribed declined by 1.7% per year in females and 1.8% in males. Conclusions Decreasing frequency of consultation and antibiotic prescription for colds, rhinitis and ‘URTI’ continues to drive a reduction in the rate of antibiotic utilization for RTIs.

Clopidogrel discontinuation after acute coronary syndromes: frequency, predictors and associations with death and myocardial infarction—a hospital registry-primary care linked cohort (MINAP–GPRD)

Aims Adherence to evidence-based treatments and its consequences after acute myocardial infarction (MI) are poorly defined. We examined the extent to which clopidogrel treatment initiated in hospital is continued in primary care; the factors predictive of clopidogrel discontinuation and the hazard of death or recurrent MI. Methods and results We linked the Myocardial Ischaemia National Audit Project registry and the General Practice Research Database to examine adherence to clopidogrel in primary care among patients discharged from hospital after MI (2003–2009). Hospital Episode Statistics and national mortality data were linked, documenting all-cause mortality and non-fatal MI. Of the 7543 linked patients, 4650 were prescribed clopidogrel in primary care within 3 months of discharge. The adjusted odds of still being prescribed clopidogrel at 12 months were similar following non-ST-elevation myocardial infarction (NSTEMI) 53% (95% CI, 51–55) and ST-elevation myocardial infarction (STEMI) 54% (95% CI, 52–56), but contrast with statins: NSTEMI 84% (95% CI, 82–85) and STEMI 89% (95% CI, 87–90). Discontinuation within 12 months was more frequent in older patients [>80 vs. 40–49 years, adjusted hazard ratio (HR) 1.50 (95% CI, 1.15–1.94)] and with bleeding events [HR 1.34 (95% CI, 1.03–1.73)]. 18.15 patients per 100 person-years (95% CI, 16.83–19.58) died or experienced non-fatal MI in the first year following discharge. In patients who discontinued clopidogrel within 12 months, the adjusted HR for death or non-fatal MI was 1.45 (95% CI, 1.22–1.73) compared with untreated patients, and 2.62 (95% CI, 2.17–3.17) compared with patients persisting with clopidogrel treatment. Conclusion This is the first study to use linked registries to determine persistence of clopidogrel treatment after MI in primary care. It demonstrates that discontinuation is common and associated with adverse outcomes.

Comparative Performance of ATRIA, CHADS2, and CHA2DS2-VASc Risk Scores Predicting Stroke in Patients With Atrial Fibrillation: Results From a National Primary Care Database.

BACKGROUND Previous studies report that CHADS2 and CHA2DS2-VASc risk scores have similar discriminating ability (C statistic ∼0.6). Recently a clinically based risk score, the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study risk score, was developed and validated. OBJECTIVES This study compared predictive ability of CHA2DS2-VASc and CHADS2 ischemic stroke risk scores with ATRIA stroke risk score and their implications for anticoagulant treatment in patients with atrial fibrillation (AF). METHODS Patients with AF not using warfarin were included from the Clinical Practice Research Datalink database, 1998 to 2012. Patients were followed from AF diagnosis until occurrence of ischemic stroke, prescription of warfarin, death, or the studys end. Independent predictors of ischemic stroke were identified and the c-index and net reclassification improvement were calculated. RESULTS A total of 60,594 patients with AF were included. Annualized stroke rate was 2.99%. Event rates for moderate- and high-risk categories for CHA2DS2-VASc were lower than those of the ATRIA and CHADS2. Age and previous stroke most strongly predicted ischemic stroke. C statistics for the full point scores were 0.70 (95% confidence interval [CI]: 0.69 to 0.71) for the ATRIA risk score, 0.68 (95% CI: 0.67 to 0.69) for CHADS2, and 0.68 (95% CI: 0.67 to 0.69) for CHA2DS2-VASc risk score. The net reclassification improvement was 0.23 (95% CI: 0.22 to 0.25) for ATRIA compared with CHA2DS2-VASc. CONCLUSIONS The ATRIA score performed better in the U.K. Clinical Practice Research Datalink AF cohort. It more accurately identified low-risk patients than the CHA2DS2-VASc score, which assigned these patients to higher-risk categories. Such reclassification of stroke risk could prevent overuse of anticoagulants in very low stroke risk patients with AF.

Risk of aplastic anemia in patients using antiepileptic drugs.

Summary:  Purpose: To assess the association between exposure to antiepileptic drugs (AEDs) and the occurrence of aplastic anemia.

Upper Gastrointestinal Adverse Events and Cyclical Etidronate

PURPOSE Recently, there have been several published case reports of esophagitis associated with the use of aminobisphosphonates. The objective of this study was to evaluate the upper gastrointestinal (GI) safety of cyclical etidronate, an alkylbisphosphonate, in routine clinical practice. PATIENTS AND METHODS Information was obtained from 550 general practices in the United Kingdom that provide the medical records to the General Practice Research Database. A group of 7977 cyclical etidronate takers and 2 age-, gender-, and practice-matched control groups (1 with osteoporosis and 1 without) were analyzed. RESULTS For cyclical etidronate takers, the average age was 71.6 years and total follow-up was 10,328 person-years. The risk of upper GI events (inflammation or ulcer of esophagus, stomach, or duodenum) was comparable between patients taking etidronate and the two control groups. The adjusted relative risk of upper GI events was 0.92 (95% confidence interval [CI] 0.78 to 1.09) for etidronate takers compared with osteoporosis controls and 1.12 (CI 0.91 to 1.37) compared to nonosteoporosis controls. For esophagitis and esophageal ulcers, the relative risks were 0.83 (CI 0.64 to 1.08) and 0.97 (CI 0.71 to 1.31) respectively. The incidence of upper GI events during nonsteroidal anti-inflammatory drug (NSAID), aspirin, or corticosteroid use was similar across the three groups. The upper GI risks of etidronate NSAID users were 0.71 (CI 0.45 to 1.11) and 2.06 (CI 0.98 to 4.35) compared with NSAID users in the two control groups. CONCLUSIONS These results support the GI tolerability and safety profile of cyclical etidronate in routine clinical practice. Concomitant use of cyclical etidronate with NSAIDs, aspirin, or corticosteroids did not increase the incidence of upper GI events.