Emiliano Sessa

Adherence to Antihypertensive Medications and Cardiovascular Morbidity Among Newly Diagnosed Hypertensive Patients

Background— Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. Methods and Results— Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18 806 newly diagnosed hypertensive patients ≥35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories—high (proportion of days covered, ≥80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, ≤40%)—and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly (P<0.001) associated with high adherence to antihypertensive treatment. Compared with their low-adherence counterparts, only high adherers reported a significantly decreased risk of acute cardiovascular events (hazard ratio, 0.62; 95% CI, 0.40 to 0.96; P=0.032). Conclusions— The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits.

Prevalence of Comorbidities in Patients with Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is associated with many comorbidities, but the percentage of COPD patients who develop comorbidities has not been clearly defined. Objectives: We aimed to examine the relationship between COPD and comorbidities using information obtained from the Health Search Database (HSD) owned by the Italian College of General Practitioners (SIMG), which stores information on about 1.5% of the total Italian population served by general practitioners. Methods: We conducted a population-based retrospective study using information obtained from the HSD. The software system used codes all the diagnostic records using the 9th Revision of the International Classification of Diseases. Results: Compared to the non-COPD people, COPD patients were at increased risk for cardiovascular events [ischemic heart disease (6.9% in the general population vs. 13.6% in COPD patients), cardiac arrhythmia (6.6% in the general population vs. 15.9% in COPD patients), heart failure (2.0% in the general population vs. 7.9% in COPD patients), and other forms of heart disease (10.7% in the general population vs. 23.1% in COPD patients); with a higher impact of COPD in the elderly]; non-psychotic mental disorders, including depressive disorders (29.1% in the general population vs. 41.6% in COPD patients; with a higher impact of COPD on women aged <75 years); diabetes mellitus (10.5% in the general population vs. 18.7% in COPD patients); osteoporosis (10.8% in the general population vs. 14.8% in COPD patients), with a higher impact of COPD on women aged <75 years, and malignant pulmonary neoplasms (0.4% in the general population vs. 1.9% in COPD patients). Conclusions: Our results indicate that COPD is a risk factor for these comorbid conditions.

Secondary Prevention of Stroke in Italy: A Cross-Sectional Survey in Family Practice

Background— Hypertension control and antiplatelet or oral anticoagulant drugs are the basis for secondary prevention of cerebrovascular events. Family physicians (FPs) are usually involved in both aspects of prevention, but no research has been carried out in Italy to evaluate the behavior of FPs in this field of prevention. Methods— Data concerning 318 Italian FPs and 465 061 patients were extracted from the Health Search Database. Patients with coded diagnoses of stroke and transient ischemic attack (TIA) were selected. Demographic records and information regarding presence of concurrent disease and medical records were also obtained. Logistic regression analyses were carried out to assess whether conditions exist that make appropriate control of blood pressure (BP) and prescription of antiplatelet or anticoagulant drugs more likely. Results— We selected 2555 patients with diagnosis of stroke and 2755 with TIA. Among all of the subjects, 32.6% had no BP recorded. Among the remaining subjects, 58.7% reported uncontrolled BP. Isolated systolic hypertension has been shown in 68.8% of patients with uncontrolled BP. Antiplatelet and anticoagulant drugs were prescribed in 72% of these cases. Factors that made the prescription significantly more unlikely were diagnosis of TIA (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.41 to 0.54), total invalidity (OR, 0.66; 95% CI 0.56 to 0.78), and time from event of 5 years or more (OR, 0.81; 95% CI, 0.70 to 0.94). Conclusions— Italian FPs could improve secondary prevention of cerebrovascular accidents. The primary target of intervention should be the control of systolic BP, and the group of patients with unacceptably high BP should be given priority. All of these patients should have been prescribed antiplatelet drugs or anticoagulant agents, except in cases of extremely short life expectancy or substantial contraindications.

Antipsychotic prescribing pattern among Italian general practitioners: a population-based study during the years 1999–2002

ObjectivesTo assess the antipsychotic use and the prevalence/incidence of antipsychotic drug users in Italy during the years 1999–2002. To estimate the persistence with antipsychotic medications, and to measure their off-label use.MethodsWe selected 465,061 individuals registered by June 2002 in the lists of 320 general practitioners, homogeneously distributed throughout Italy, from the Health Search Database. We measured the antipsychotic drug consumption, calculated as defined daily dose (DDD) per 1000 inhabitants per day. We also calculated the number of individuals receiving at least one antipsychotic prescription, to estimate the annual prevalence and incidence of antipsychotic users. Among incident users, we evaluated the percentage of patients adherent to drug label indications and the average duration of treatment, estimated as medical possession ratio (MPR).ResultsAtypical antipsychotic use has continuously increased from 1999 to 2002. Women, older people and patients affected by psychotic disorders other than schizophrenia were seen to be more likely to receive antipsychotic prescriptions. Persistence with atypical drug treatment (MPR=0.213 in 2002) appeared longer than that of typical drugs (0.169). The percentage of patients adherent to drug label indications was significantly higher among typical antipsychotic users (P<0.001). The most common off-label use for atypical drug was senile dementia.ConclusionAtypical drug use has been continuously expanding over the years 1999–2002, particularly in older people with dementia. The rapidly increasing use of this new class of antipsychotics highlights the need for a better evaluation regarding their safety profile and a better definition of their role in psychiatric treatments.

Risk of stroke with typical and atypical anti-psychotics: a retrospective cohort study including unexposed subjects

The purpose of the study was to investigate the risk of stroke with typical and atypical anti-psychotics in elderly subjects, weighting for a number of known risk factors, including dementia. Data were retrospectively drawn from the primary care setting from the Health Search Database, which stores information on about 1.5% of the total Italian population served by general practitioners. All elderly patients (65+ years) prescribed an anti-psychotic in monotherapy from January 2000 to June 2003 were selected for the study. A cohort of patients not exposed to anti-psychotics was taken from the same database. Subjects who had previously had a stroke were excluded. The main outcome measure was the incidence of first-ever stroke during exposure to an anti-psychotic.The sample included non-users (69,939), users of atypicals (599), butyrophenones (749), phenotiazines (907) and substituted benzamides (1,968). The crude incidence of stroke in subjects not exposed to anti-psychotics was 12.0/1000 person-years. Risk was significantly higher for those on butyrophenones (47.1/1000), phenotiazines (72.7/1000) and in the atypical anti-psychotic group (47.4/1000). Substituted benzamides had an almost significant higher risk (25.0/1000). Cox regression modelling, weighting for demographic and clinical variables with non-users as the reference group, showed that the risk for stroke was 5.79 times for phenotiazines, 3.55 times for butyrophenones, and 2.46 times for atypicals. Clinicians should be cautious in prescribing phenotiazines and butyrophenones in elderly patients, since the risk for stroke would seem comparable or even greater than with atypicals.

Mental disorders associated with benzodiazepine use among older primary care attenders: A regional survey

BackgroundBenzodiazepines (BDZs) are among the most commonly prescribed drugs in the elderly and their use is often too prolonged according to current international guidelines.MethodsWe investigated the pattern of use of BDZs among 65- to 84-year-old attenders at 40 Italian primary care practices who answered positively in a questionnaire on the use of anxiolytic/hypnotic drugs and successfully completed the PRIME-MD questionnaire. The survey lasted 6 months, from February to July 2001.ResultsOf the 1,156 subjects who completed the PRIME-MD, 748 subjects were positive for at least one psychiatric diagnosis. A depressive disorder was present in 36.5% of all PRIME-MD completers and in about one-third of cases represented by major depression, whereas anxiety disorders, somatoform disorders and alcohol abuse accounted for 18.2%, 8.1% and 1.7% of all PRIME-MD completers, respectively. Most patients were first prescribed BDZs by their General Practitioners (GPs) for each diagnostic group. However, patients with pure anxiety started BDZ treatment during hospitalisation more often (19.7%) than patients with depressive disorders (13.7 %). Moreover, patients with comorbid anxiety and depressive disorders (CADD) were most likely to receive their first BDZ prescription from a psychiatrist (15.7 %). Sleep disturbances were present in at least 50% of cases (and up to 86 %) in each diagnostic group. About 75% of prescriptions concerned anxiolytic BDZ or medium/long-acting BDZ. Most patients with anxiety, CADD and depression used night-time BDZ (65.2%, 56.9 % and 60.5%, respectively). The prevalence of chronic use of BDZs was equally high in all categories of psychiatric disorder (about 90 % for each), showing that the vast majority of patients, irrespective of the diagnosis, had been using BDZs for years.ConclusionsBDZs are widely prescribed for elderly people by their GPs, often for a considerable length of time. The evidence that many BDZ consumers suffer from a depressive or an anxiety disorder, or both, could be a starting point for encouraging a rational prescription in accordance with international guidelines.

Primary care of the patient with chronic obstructive pulmonary disease in Italy

Using a general practice research database with general practitioner (GP) clinical records, it has been observed that among the 617,280 subjects registered with 400 Italian GPs, 15,229 (2.47%) patients were suffering from chronic obstructive pulmonary disease (COPD). Of these, 67.7% had a chest radiograph at least once in a period of 10 years (1997-2006), while in the same period only 31.9% had a spirometry, 29.9% had a visit to a specialist, and 0.94% had a visit to an allergologist. From 1997 to 2006, 7.5% of patients with COPD, especially the oldest ones, were hospitalized at least once for the disease, although 44.0% of all patients with COPD were hospitalized for other pathologies. With regard to treatment, in 2006, 10,936 (71.1%) of COPD patients received at least one drug for their disease (drugs classified within the R03 therapeutic pharmacological subgroup of the Anatomical Therapeutic Chemical Classification). In particular, salmeterol/fluticasone was prescribed 6441 times, tiotropium 4962, theophylline 3142, beclomethasone 2853, salbutamol 2256, formoterol 2191, salbutamol/beclomethasone 2129, oxitropium 1802 and formoterol/budesonide 1741 times. Based on these findings, the level of COPD management in Italy seems to fall short of recommended international COPD guidelines. In particular, it appears that GPs usually prescribe treatment without the use of spirometry, and/or without taking into account the severity of airway obstruction. It must also be noted that, in general, patients with COPD are undertreated.

Safety profile of the fluoroquinolones: analysis of adverse drug reactions in relation to prescription data using four regional pharmacovigilance databases in Italy.

AbstractBackground: Fluoroquinolones are widely used both in primary care and in hospital settings. Since the last comparison performed in Italy on the safety profiles of different fluoroquinolones, a new molecule, prulifloxacin, has been introduced into the market and several warnings concerning this class of drugs have been released. The aim of this study was to reassess the safety profiles of fluoroquinolones using the database of the Italian Interregional Group of Pharmacovigilance (IGP) and the administrative data of fluoroquinolone prescriptions. Methods: All adverse drug reactions (ADRs) reported in four Italian regions (Lombardy, Veneto, Emilia Romagna and Tuscany) were retrieved from the IGP database. Consumption data (defined daily dose [DDD]/1000 inhabitants/ day) were used as denominators. Both single reports and all ADRs (classified by System Organ Classes and MedDRA® Preferred Term [PT]) due to fluoroquinolones were considered as numerators of each analysis, comparing two periods (2005 vs 2006). All fluoroquinolones with at least ten reports per year were included in the analysis. Results: On the basis of 272 reports (532 single ADRs or PTs), patients did not show any statistically significant differences between 2005 and 2006 in terms of sex, age and number of concurrent medications. After adjustment for drug consumption, moxifloxacin showed the highest reporting rate (84.6 reports/ DDD/1000 inhabitants/day; 15.4 serious reports/DDD/1000 inhabitants/day) followed by prulifloxacin (72.2; 22.2 serious) and levofloxacin (55.3; 30.6 serious) in 2005. An increment of ADR/report rates was observed over the 2 years for all fluoroquinolones except prulifloxacin, which had the lowest ADR reporting rate in 2006 (25.0; 12.5 serious). In 2006, the rate of serious ADRs associated with prulifloxacin was lower than with ciprofloxacin, while in 2005 serious events were almost equal for both compounds (55.6 vs 47.6 serious ADRs/DDD/1000 inhabitants/day). Ciprofloxacin showed the highest proportion of cutaneous PTs (e.g. rash, exanthema). Tendinopathies were mainly due to levofloxacin. Conclusions: These data suggest that different fluoroquinolones are characterized by different rates and types of ADRs. Among them, prulifloxacin was associated with more ADRs than other fluoroquinolones in 2005 but with fewer ADRs in 2006, when its consumption increased. Although these findings may represent an encouraging perspective towards a more appropriate use of fluoroquinolones because of their individual safety profiles, further pharmacoepidemiological studies must be performed to substantiate these results.

Out of hospital sudden cardiac death in Italy: a population-based case-control study.

Background Sudden cardiac death (SCD) is a major cause of death in western countries, with coronary heart disease (CHD) being the basis of over 70% of SCD. Incidence in high-CHD risk countries has already been studied, but this information is not available for Mediterranean low-CHD risk countries. Incidence is of paramount importance when cost-effectiveness rate of actions against SCD must be estimated. Methods We estimated the incidence of SCD and its potential risk associated with clinical variables, by a means of a case–control study in a general practice setting. The enrolled general practitioners (GPs) provided data about the total number of their patients, and identified all their patients who suffered an out-of-hospital SCD during the previous 365 days. Two age-matched and gender-matched controls visiting GPs office after the SCD selection were also selected. We used a structured questionnaire to obtain information about potential risk factors for SCD. Covariates that were univariately associated with SCD were included in the multivariate regression analyses. Results In a population of 297 340 (age greater than 14 years), a total of 230 cases were identified (0.77 per 1000 individuals), mostly occurring at home and among persons with known high cardiovascular risk. In the multivariate analysis only CHD (OR: 1.67; 95% CI: 1.09–2.58), arrhythmia (OR: 2.2; 95% CI: 1.3–3.9), obesity (OR: 2.3; 95% CI: 1.5–3.6), alcohol abuse (OR: 1.8; 95% CI: 1.2–2.7), and family history of CHD (OR 3.1; 95% CI: 1.8–5.3) resulted in a significant association with SCD. Conclusions The incidence of SCD in Italy is lower than that reported in high-CHD risk population, most of the cases occurring at home and among persons with known high cardiovascular risk. Implementing recommendations for these patients seems to be the most effective strategy to reduce the incidence of SCD.

A national survey on aspirin patterns of use and persistence in community outpatients in Italy

Background: Aspirin is recommended as preventive therapy in patients with cardiovascular diseases (CVD), diabetes mellitus, and high cardiovascular risk due to multiple risk factors. However, the benefits of aspirin might be affected by its inappropriate use. Real-life information on aspirin use is therefore needed as an audit tool aimed to maximize the benefits and minimize the risks. Design: Retrospective cross-sectional and cohort study. Methods: Primary care data were obtained from 400 Italian general practitioners (GPs) providing information to the Health Search/CDS Longitudinal Patients Database. Prevalence of use was assessed in individuals aged 18 years and older, registered in the GP’s list at the beginning of the observation period (year 2005). As potential correlates of aspirin use, clinical and demographic variables were also recorded. Logistic regression analysis was conducted to assess the relationship between such covariates and aspirin use. Persistence to aspirin treatment was examined among newly prescribed aspirin users during the years 2000–04. Results: On a total sample of 540,984 patients, 45,271 (8.3%) were prescribed at least once with aspirin. On 35,473 patients with previous CVD, 51.7% were treated with aspirin, whereas only 15.2% of 151,526 eligible patients free of CVD received an aspirin prescription. In primary prevention, prevalence of aspirin use was significantly associated with the increased number of cardiovascular risk factors either among diabetic (p < 0.001) or non-diabetic (p < 0.001) patients. A negative association has been observed among patients with contraindication to aspirin use. Only 23.4% of patients at 1 year and 12.2% at 2 years remained persistent with aspirin use, although most of first-time users reported an intermittent use. Conclusion: Underuse and discontinuation of aspirin treatment is common among eligible patients. Increased cardiovascular risk only partially influences aspirin management. An effort aimed to improve appropriate aspirin use is likely to provide major benefits.