Prescribers' compliance with summary of product characteristics of dabigatran, rivaroxaban and apixaban-A European comparative drug utilization study.

Despite a tremendous increase of direct oral anticoagulants (DOACs) prescriptions in recent years, only few data is available analysing prescribers' adherence to Summary of Product Characteristics (SmPC). We aimed to assess adherence to registered indications, contraindications, special warnings/precautions, and potential drug-drug interactions for three DOAC compounds (dabigatran, rivaroxaban, and apixaban) in six databases of five European countries (The Netherlands, United Kingdom, Spain, Denmark, and Germany). We included adult patients (≥18 years) initiating DOACs between 2008 and 2015. For several SmPC items, broad definitions were used due to ambiguous SmPC terms or lacking data in some databases. Within the study period, a DOAC was initiated in 407 576 patients (rivaroxaban: 240 985 (59.1%), dabigatran: 95 303 (23.4%), and apixaban: 71 288 (17.5%)). In 2015, non-valvular atrial fibrillation was the most common indication (>60% in most databases). For the whole study period, a substantial variation between the databases was found regarding the proportion of patients with at least one contraindication (inter-database range [IDR]: 8.2%-55.7%), with at least one special warning/precaution (IDR: 35.8%-75.2%) and with at least one potential drug-drug interaction (IDR: 22.4%-54.1%). In 2015, the most frequent contraindication was "malignant neoplasm" (IDR: 0.7%-21.3%) whereas the most frequent special warning/precaution was "prescribing to the elderly" (≥75 years; IDR: 25.0%-66.4%). The most common single compound class interaction was "concomitant use of non-steroidal anti-inflammatory drugs" (IDR: 3.0%-25.3%). Contraindications, special warnings/precautions, and potential drug-drug interactions were present in a relevant number of new DOAC users. Due to broad definitions used for some SmPC terms, overall proportions for contraindications are prone to overestimation. However, for unambiguous SmPC terms documented in the databases sufficiently, the respective estimates can be considered valid. Differences between databases might be related to "true" differences in prescription behaviour, but could also be partially due to differences in database characteristics.

Incidence of direct oral anticoagulant use in patients with nonvalvular atrial fibrillation and characteristics of users in 6 European countries (2008-2015): A cross-national drug utilization study.

AIMS: To estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries. METHODS: Longitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed. RESULTS: A total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93-2.60 and 0.11-8.71 users/10 000 (2011-2015) for dabigatran and rivaroxaban, respectively, and from 0.01-8.12 users/10 000 (2012-2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany). CONCLUSION: Overall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH).

Habitual coffee consumption and 24-h blood pressure control in older adults with hypertension.

BACKGROUND & AIMS: In normotensive and hypertensive individuals, blood pressure (BP) rises acutely during a few hours following coffee or caffeine consumption. However, the effect of habitual coffee consumption on BP and BP control is uncertain. The aim of this study was to assess the association of habitual coffee consumption on 24-h BP and BP control among older adults with hypertension. METHODS: Data were taken from the Seniors-Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), a cross-sectional study conducted in 2012 among 1164 individuals aged ≥63 years. Habitual coffee consumption was assessed with a validated diet history. BP was recorded by 24-h ambulatory monitoring. Ambulatory hypertension was defined as BP ≥ 130/80 mm Hg or being under antihypertensive treatment, and uncontrolled BP was deemed as BP ≥ 130/80 mm Hg among hypertensives. Analyses were performed with linear and logistic regressions adjusted for the main confounders, including diet, time since diagnosis of hypertension and the number of antihypertensive drugs. RESULTS: Among the 715 hypertensive participants, those consuming ≥3 cups of coffee/day showed higher 24-h systolic BP (beta: 3.25 mm Hg, p value = 0.04) and diastolic BP (beta: 2.24 mm Hg, p value = 0.02) than non-coffee drinkers. Compared to non-coffee drinkers, the odds ratios (95% confidence interval) for uncontrolled BP among those consuming 1, 2, and ≥3 cups of coffee/day were, respectively: 1.95 (1.15-3.30), 1.41 (0.75-2.68), and 2.55 (1.28-5.09); p for trend = 0.05. The association was similar among individuals who were smokers, had excess weight (body mass index ≥25 kg/m2), low adherence to the Mediterranean diet, or hypercholesterolemia. No association was found between coffee consumption and having a non-dipper BP pattern (<10% nocturnal decline in BP) among hypertensives. CONCLUSION: Habitual coffee consumption was associated with uncontrolled BP in a hypertensive older population.

Validity and reproducibility of a Spanish dietary history.

OBJECTIVE: To assess the validity and reproducibility of food and nutrient intake estimated with the electronic diet history of ENRICA (DH-E), which collects information on numerous aspects of the Spanish diet. METHODS: The validity of food and nutrient intake was estimated using Pearson correlation coefficients between the DH-E and the mean of seven 24-hour recalls collected every 2 months over the previous year. The reproducibility was estimated using intraclass correlation coefficients between two DH-E made one year apart. RESULTS: The correlations coefficients between the DH-E and the mean of seven 24-hour recalls for the main food groups were cereals (r = 0.66), meat (r = 0.66), fish (r = 0.42), vegetables (r = 0.62) and fruits (r = 0.44). The mean correlation coefficient for all 15 food groups considered was 0.53. The correlations for macronutrients were: energy (r = 0.76), proteins (r= 0.58), lipids (r = 0.73), saturated fat (r = 0.73), monounsaturated fat (r = 0.59), polyunsaturated fat (r = 0.57), and carbohydrates (r = 0.66). The mean correlation coefficient for all 41 nutrients studied was 0.55. The intraclass correlation coefficient between the two DH-E was greater than 0.40 for most foods and nutrients. CONCLUSIONS: The DH-E shows good validity and reproducibility for estimating usual intake of foods and nutrients.

Sleep quality and the metabolic syndrome: the role of sleep duration and lifestyle.

BACKGROUND: This study examined the association between sleep quality and the metabolic syndrome and whether if it is independent of sleep duration and if it can be explained by lifestyles linked to sleep quality. METHODS: Cross-sectional study conducted from 2008 to 2010 with 10 342 individuals representative of the population aged ≥18 years in Spain. Poor sleep quality was ascertained through self-reported difficulty falling asleep, difficulty maintaining sleep and sleeping pill consumption. Metabolic syndrome was defined according to the recent harmonized definition. Analyses were conducted with logistic regression and adjusted for the main confounders. RESULTS: Difficulty falling asleep was associated with higher frequency of metabolic syndrome after adjustment for sociodemographic variables, lifestyle and diagnosed morbidity [odds ratio (OR) = 1.25; 95% confidence interval (CI) = 1.06-1.47]. The association was slightly attenuated after further adjusting for sleep duration (OR = 1.23; 95% CI = 1.04-1.46) and held after additional adjustment for energy intake, adherence to a Mediterranean dietary pattern, energy spent in physical activity and time watching TV (OR = 1.20; 95% CI = 1.01-1.42). No associations were found between metabolic syndrome and other sleep quality indicators. Difficulty falling asleep was associated with high blood pressure in the fully adjusted analyses (OR = 1.17; 95% CI = 1.00-1.37) but not with the rest of components of metabolic syndrome. CONCLUSIONS: Difficulty falling asleep is associated with metabolic syndrome and, in particular, with high blood pressure. This association is independent of sleep duration and is not due to lifestyles related to poor sleep. This finding should be replicated in prospective studies using objective sleep measures; also, the influence of antihypertensive and lipid-lowering drug treatment on this association should be further studied.

Food sources of sodium, saturated fat and added sugar in the Spanish hypertensive and diabetic population.

OBJECTIVES: Previous research has shown that the diet of hypertensive and diabetic patients has a low accordance with the main nutritional recommendations, mostly due to the high intake of sodium, saturated fat and added sugars. This is the first study to identify the main food sources of these nutrients in these patients. METHODS: Cross-sectional study conducted in 2008-2010 in a representative sample of the Spanish adult population, including 2323 patients with hypertension and 635 with diabetes. The habitual diet was assessed using a validated diet history. The intake of sodium, saturated fat and added sugars was estimated with Spanish food composition tables. RESULTS: The hypertensive and diabetic population showed, respectively, an intake of 2.9 and 3.1 g/day of sodium, 26 and 26 g/day of saturated fat, and 33 and 24 g/day of added sugar. In hypertensive and diabetic patients, respectively, most sodium intake came from bread (35%, 34%), raw-cured sausages (15%, 15%), cooked sausages (6%, 7%), and soup (5%, 6%). The main sources of saturated fat were cured cheese (13%, 13%), bakery products (12%, 11%), red meat (10%, 11%), raw-cured sausages (8%, 9%) and whole milk (4%, 4%). The food groups that most contributed to added sugar intake were sugar directly added to coffee and other beverages (27%, 19%), bakery products (15%, 19%), sugary soft drinks (10%, 13%), and whole yogurt (9%, 12%). The main food sources of nutrients were similar in all sex and age groups. CONCLUSIONS: In patients with hypertension and diabetes, the intake of sodium, saturated fat and added sugar can be substantially reduced by prioritizing low-salt varieties of bread, reducing the consumption of bakery products and sausages, replacing cured cheese and other whole dairy products by low-fat products, using non-sugary sweeteners, and substituting sugar-free soft drinks, or plain water, for sugary sodas.

Life-course socioeconomic position and change in quality of life among older adults: evidence for the role of a critical period, accumulation of exposure and social mobility.

BACKGROUND: This study evaluates the influence of socioeconomic position (SEP) over the life course on change in health-related quality of life (HRQoL) in older adults. METHODS: A prospective cohort of 2117 individuals aged 60 years and over. In 2001, SEP was measured over the life course as social class in childhood (approximated by father's occupation), as educational level completed and as adult social class (occupation of household head). HRQoL was measured with the SF-36 health questionnaire. Changes from 2001 to 2003 in the scores for the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 were calculated, and individuals were classified into three categories: decline (decrease of >5 points), no change (change of -5 to +5 points) and improvement (increase of >5 points) in HRQoL. RESULTS: After adjustment for baseline HRQoL, lifestyle, chronic illness, educational level and adult social class, low childhood social class was associated with a higher risk of both a decline and an improvement in the SF-36 PCS and MCS. The risk of decline in PCS and MCS and of improvement in MCS increased with the cumulative number of adverse SEP over the life course. Subjects who rose in social class from childhood to adulthood showed the greatest improvement on the SF-36 PCS and MCS. CONCLUSION: These results on the relation between SEP and changes in HRQoL in older adults support the three models proposed to explain health inequalities over the life course: the existence of critical periods, the accumulation of adverse SEP and social mobility.

Change in health-related quality of life as a predictor of mortality in the older adults.

PURPOSE: We examined whether changes in health-related quality of life (HRQL) predict subsequent mortality among the Spanish elderly. METHODS: Prospective cohort study of 2,373 persons, representative of the Spanish population aged 60 and older. HRQL was measured in 2001 and 2003 using the SF-36 health questionnaire. Cox regression models were used to examine the association of changes in the physical and mental component summary (PCS and MCS) scores of HRQL from 2001 to 2003 with all-cause mortality through 2007. RESULTS: Two hundred twelve deaths were ascertained from 2003 to 2007. The hazard ratios for mortality across categories of PCS change were as follows: 2.12 (95% confidence interval [CI] 1.39-3.24) for a > 10-point decline; 1.51 (1.01-2.28) for a 6- to 10-point decline; 1 for the reference category, a change of -5 to +5 points; 0.83 (0.51-1.34) for a 6- to 9-point improvement and 0.68 (0.42-1.09) for a > 10-point improvement; P for linear trend <0.001. The associations between changes in the MCS and mortality showed the same direction, but were of a lower magnitude and attained statistical significance (P < 0.05) only for a > 10-point decline in MCS. CONCLUSIONS: Changes in HRQL predict mortality in the older adults. A decline in HRQL should alert to a worse vital prognosis and stimulate the search for the possible determinants of such decline.

[Cardiovascular mortality attributable to high blood pressure in Spanish population over 50]. / Mortalidad cardiovascular atribuible a la presión arterial elevada en la población española de 50 años o más.

BACKGROUND AND OBJECTIVE: Cardiovascular mortality attributable to high blood pressure in Spain is not available at present. PATIENTS AND METHOD: Population attributable risk and number of cardiovascular deaths attributable to high systolic blood pressure (> or = 120 mmHg) were estimated for the Spanish population aged 50-89 years, according to classical formulae. Relative risk data were drawn from the Prospective Studies Collaboration, meta-analysis of 61 studies on blood pressure and mortality, with data on one million subjects (30,000 from South Europe) with no prior vascular disease. Blood pressure prevalence was drawn from 2 nationwide surveys in Spain, for subjects aged 50-59 years and 60-89 years old, respectively. Cardiovascular deaths occurred in Spain were drawn from official statistics (year 2004). RESULTS: The number of annual cardiovascular deaths attributable to high blood pressure was 44,401, which represents 54% of the carFdiovascular deaths occurred in people over 50 years: 17,312 for ischemic heart disease, 15,599 for stroke, and 11,490 for other cardiovascular diseases. The highest number of attributable deaths lie in hypertension grade 1 and 2 (32,638) and in those over 70 years (36,345). Normal and high-normal blood pressure accounted for 6% of all attributable cardiovascular deaths. CONCLUSIONS: One in 2 cardiovascular deaths occurred annually in Spanish individuals over 50 years are attributable to high blood pressure, 90% of them are attributable to hypertension.

Mortalidad cardiovascular atribuible a la presión arterial elevada en la población española de 50 años o más / Cardiovascular mortality attributable to high blood pressure in Spanish population over 50

FUNDAMENTO Y OBJETIVO: No se dispone de información actual sobre la mortalidad cardiovascularatribuible a la presión arterial elevada en España.PACIENTES Y MÉTODO: Se han estimado, mediante fórmulas convencionales, los riesgos atribuiblespoblacionales y el número de muertes cardiovasculares relacionadas con cifras elevadas de presiónarterial sistólica ( 120 mmHg) en la población de 50-89 años de España. Los datos sobre riesgos relativos proceden del Prospective Studies Collaboration, metaanálisis de 61 estudios de presión arterial y mortalidad, con datos de un millón de personas (30.000 del sur de Europa) sin antecedentes de enfermedad vascular. Las prevalencias de la presión arterial proceden de 2 estudios representativos de la población española para personas de 50-59 y 60-89 años de edad, respectivamente. El número de muertes de causa cardiovascular ocurridas se ha tomado del Instituto Nacional de Estadística (año 2004).RESULTADOS: Anualmente un total de 44.401 muertes de causa cardiovascular son atribuibles a la presión arterial elevada, lo que representa el 54% de la mortalidad cardiovascular en mayores de 50 años: 17.312 por cardiopatía isquémica, 15.599 por enfermedad cerebrovascular y 11.490 por otras enfermedades cardiovasculares. El mayor número de muertes atribuibles corresponde a las categorías de hipertensión grados 1 y 2 (32.638) y a los mayores de 70 años (36.345), y las presiones normal y normal-alta explican un 6% de todas las muertes atribuibles.CONCLUSIONES: Una de cada 2 muertes de causa cardiovascular ocurridas anualmente a los individuosmayores de 50 años son atribuibles a la presión arterial elevada, y el 90% de ellas son atribuibles a la hipertensión

BACKGROUND AND OBJECTIVE: Cardiovascular mortality attributable to high blood pressure in Spainis not available at present.PATIENTS AND METHOD: Population attributable risk and number of cardiovascular deaths attributableto high systolic blood pressure ( 120 mmHg) were estimated for the Spanish population aged 50-89 years, according to classical formulae. Relative risk data were drawn from the Prospective Studies Collaboration, meta-analysis of 61 studies on blood pressure and mortality,with data on one million subjects (30,000 from South Europe) with no prior vascular disease. Blood pressure prevalence was drawn from 2 nationwide surveys in Spain, for subjects aged 50-59 years and 60-89 years old, respectively. Cardiovascular deaths occurred in Spain were drawn from official statistics (year 2004).RESULTS: The number of annual cardiovascular deaths attributable to high blood pressure was 44,401, which represents 54% of the cardiovascular deaths occurred in people over 50 years: 17,312 for ischemic heart disease, 15,599 for stroke, and 11,490 for other cardiovascular diseases. The highest number of attributable deaths lie in hypertension grade 1 and 2 (32,638) and in those over 70 years (36,345). Normal and high-normal blood pressure accounted for 6% of all attributable cardiovascular deaths.CONCLUSIONS: One in 2 cardiovascular deaths occurred annually in Spanish individuals over 50 years are attributable to high blood pressure, 90% of them are attributable to hypertension

Functional status and use of health care services: longitudinal study on the older adult population in Spain.

BACKGROUND: Follow-up studies on the association between functional status and use of health care services among the older people are scarce and have studied only a few types of service. OBJECTIVE: To examine prospectively the relationship between limitation in instrumental activities of daily living (IADL) and utilization of a wide variety of health care services among older adults in Spain. METHODS: Prospective study from 2001 to 2003 of a cohort of 2806 persons, representative of the non-institutionalized Spanish population aged 60 years and over. Limitation in IADL was measured in 2001 using the Lawton and Brody's test. Data on the use of health care services were collected in 2003 and classified into home services (home visits by physicians and nurses) and non-home services (visits to primary care physicians, visits to hospital specialists, hospital admissions, emergency care, and influenza vaccination). Analyses were performed with logistic regression and adjusted for the main confounders. RESULTS: Compared to men with no limitation in IADL, a higher percentage of those with limitation in one IADL in 2001 made use of both home (odds ratio [OR] 2.64; 95% confidence interval [95% CI] 1.73-4.03) and non-home services (OR 2.02; 95% CI 1.04-3.93) in the period 2001-2003. Limitation in one IADL among women was associated with a greater utilization of home services (OR 1.50; 95% CI 1.05-2.14) and visits to hospital specialists (OR 1.61; 95% CI 1.21-2.15). In women, however, a greater number of limited IADL at baseline was inversely associated with visits to primary care physicians in the 2-year follow-up (p for linear trend <0.001). CONCLUSION: Population aging will increase the demand for health services in general, and for home services in particular.