Ida Fortino

Cardiovascular Protection by Initial and Subsequent Combination of Antihypertensive Drugs in Daily Life Practice

Guidelines recommend a combination of 2 drugs to be used as first-step treatment strategy in high-risk hypertensive individuals to achieve timely blood pressure control and avoid early events. The evidence that this is associated with cardiovascular (CV) benefits compared with initial monotherapy is limited, however. The objective of this study was to assess whether, compared with antihypertensive monotherapy, a combination of antihypertensive drugs provides a greater CV protection in daily clinical practice. A population-based, nested case-control study was carried out by including the cohort of 209 650 patients from Lombardy (Italy) aged 40 to 79 years who were newly treated with antihypertensive drugs between 2000 and 2001. Cases were the 10 688 patients who experienced a hospitalization for CV disease from initial prescription until 2007. Three controls were randomly selected for each case. Logistic regression was used to model the CV risk associated with starting on and/or continuing with combination therapy. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients starting on combination therapy had an 11% CV risk reduction with respect to those starting on monotherapy (95% CI: 5% to 16%). Compared with patients who maintained monotherapy also during follow-up, those who started on combination therapy and kept it along the entire period of observation had 26% reduction of CV risk (95% CI: 15% to 35%). In daily life practice, a combination of antihypertensive drugs is associated with a great reduction of CV risk. The indication for using combination of blood pressure drugs should be broadened.

Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database

Purpose:  To estimate the prevalence of potentially severe drug–drug interactions (DDIs) and their relationship with age, sex and number of prescribed drugs.

Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly.

Abstract: Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

Drug utilization and polypharmacy in an Italian elderly population: the EPIFARM-elderly project†‡

To investigate the prescribing patterns and the prevalence of polypharmacy in community‐dwelling elderly people, and to analyze the association of chronic medications and number of drug prescriptions with age and sex.

Prevalence, incidence and mortality of diagnosed diabetes: Evidence from an Italian population-based study

Diabet. Med. 29, 385–392 (2012)

Trends in drug prescriptions to diabetic patients from 2000 to 2008 in Italy's Lombardy Region: A large population-based study

OBJECTIVE To analyze the prescribing patterns of antidiabetic and cardiovascular medications among diabetics in the most highly populated Italian Region, from 2000 to 2008. METHODS Data were obtained from the Lombardy Region administrative health databases. The standardized prevalence of antidiabetic and cardiovascular drugs use was calculated within each study year. The prescription trends of initial treatment with antidiabetic drugs were also analyzed. RESULTS From 2000 to 2008 there was an increase in the proportion of patients treated with biguanides (from 53.4% to 66.5%; p<0.0001) while those receiving sulfonylurea decreased (from 78.6% to 56.4%; p<0.0001). A sharp increase of metformin (as monotherapy) as initial treatment was also observed (from 15.2% to 48.8%; p<0.0001). The percentage of patients receiving renin-angiotensin system inhibitors, lipid-lowering drugs and antiplatelets increased between 2000 and 2008, from respectively 45.1% to 63.3%, 13.6% to 43.2% and 21.6% to 40.9 (p<0.0001). Multivariate analyses indicated that changes in prescriptions were statistically significant for both antidiabetic and cardiovascular drugs. CONCLUSION This study documents progressive changes in the prescription of antidiabetic and cardiovascular drugs in accordance with guidelines. However, the use of metformin as first line therapy was still suboptimal and cardiovascular preventive strategies were only partially implemented in community practice.

Determinants of the drug utilization profile in the paediatric population in Italy's Lombardy Region

AIMS To evaluate the intraregional differences in drug prescribing to children and adolescents. METHODS Prescriptions reimbursed by the National Health System, involving 1543 203 children and adolescents <18 years old and dispensed during 2005 by the retail pharmacies of 15 local health units (LHU) in the Lombardy Region, were analysed. Logistic regression analysis was performed to evaluate the association between drug prescription and age, gender, prescriber, and setting. RESULTS A total of 747 790 youths (48%) received at least one drug prescription. The prescription prevalence rate was highest in children 1-5 years old (65%), decreased with increasing age to 38% in adolescents, and was slightly higher in boys than in girls. Antibiotics and anti-asthmatics were the most prescribed therapeutic classes. Amoxicillin + clavulanic acid was the most prescribed drug (18% of children; 20% of packages). Large differences were found in the drug prescription prevalence rate between the different LHUs. The rate ranged between 38.4 and 54.8%, and was not correlated to hospitalization rate in the paediatric population. Being 1-5 years old [odds ratio (OR) 4.51, 95% confidence interval (CI) 4.43, 4.58] and living in the eastern part of the region (OR 2.06, 95% CI 1.99, 2.13) were the factors associated with the highest risk of drug exposure. CONCLUSIONS The results resemble the profiles observed in other Italian contexts, in particular concerning the wide use of antibiotics and anti-asthmatics. However, large differences were found between LHUs, highlighting the need for more detailed investigations on therapeutic needs, drug use, and related variables in different geographic contexts.

Changes in trend of antipsychotics prescription in patients treated with cholinesterase inhibitors after warnings from Italian Medicines Agency. Results from the EPIFARM-Elderly Project

The objective of the study was to assess the trend of antipsychotic prescription in elderly patients taking cholinesterase inhibitors (ChEIs) from 2002 to 2008 and the changes subsequent to two main official warnings issued by the Italian Medicines Agency to restrict their use. Elderly patients aged 65-94years who received at least one prescription of ChEIs between 1 January 2002 and 31 December 2008 were selected. We used data on prescriptions from the Lombardy Region Drug Administrative Database (Italy). The first prescription of one ChEI was used as the index day to calculate the prescription of an antipsychotic. The prescription of atypical antipsychotics in patients exposed to ChEIs declined from 21.0% in 2002 to 14.6% in 2008 (OR 0.92; 95%CI:0.90, 0.94; p<0.001), while the prescribing prevalence of typicals slightly increased (OR 1.08; 95%CI:1.03, 1.13; p=0.001). In relation to the two warnings, the prevalence of patients who received a prescription of antipsychotics was significantly lower in 2005 than 2004 (23.1% vs. 28.0%; OR 0.79; 95%CI:0.73-0.86; p<0.001) and in 2007 than 2006 (19.4% vs. 23.0%; OR 0.79; 95%CI:0.73-0.86; p<0.001). After the first safety warning the prevalence of prescriptions for risperidone and olanzapine dropped significantly, and there was a significant increase for quetiapine. Haloperidol prescriptions increased, especially after the second warning. Despite regulatory warnings issued to discourage the use of antipsychotics, they are still frequently prescribed to patients taking ChEIs. Awaiting further studies to clarify their therapeutic role, physicians should prescribe antipsychotics very cautiously and only after careful risk-benefit assessment.

Anti-asthmatic drug prescriptions to an Italian paedriatic population

To estimate the prevalence and evaluate the appropriateness of anti‐asthmatic drug prescriptions in an Italian paediatric population, drug prescriptions involving 24,407 children <18 years old, dispensed during 2003 by the retail pharmacies of the local health unit in Lecco, Italy, were analysed. Children ≥6 years old receiving anti‐asthmatics were categorized into three subgroups based on the number of boxes prescribed: occasional (one box), low (two and three boxes) and high (≥four boxes) users. A logistic regression analysis was performed to estimate the relationship between the drug use patterns and formulations, antibiotic co‐prescriptions, systemic steroid prescriptions and rate of hospitalization. Anti‐asthmatic drugs were prescribed to 6594 (12%) children and adolescents; 58% of whom received only one box of the drug. Prevalence varied according to age, with the highest values at 1 and 4 years (24% and 21% respectively), and decreased to 6% in 17‐year‐old adolescents. Inhaled steroids were the most prescribed drugs (83%). The most common of these was beclomethasone. Occasional, low and high users represented 58%, 29%, and 13%, respectively, of the treated population ≥6 years old. High users were found to be at increased risk of systemic steroid prescriptions (OR 8.6) and hospital admission for asthma (OR 6.8). This study confirms that in Italy the prevalence of anti‐asthmatic prescription is much higher than prevalence of disease, indicating that anti‐asthmatics are over‐prescribed. Moreover, steroids, especially nebulized, are mainly prescribed only once in a year, supporting the idea that are prescribed not for asthma, which as chronic disease requires a chronic therapy. The approach to create subgroups on the basis of number of boxes prescribed seems to be effective in estimating asthma severity and appropriateness of the therapies.

Past use of selective serotonin reuptake inhibitors and the risk of cerebrovascular events in the elderly.

Treatment with selective serotonin reuptake inhibitors (SSRIs) has been associated with intracranial bleeding abnormalities. We investigated the relationship between past exposure to SSRIs and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 years or above with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 years or above who received antidepressant prescriptions during 2001. The two databases were linked anonymously using the individual patient code. The analysis showed that the proportion of cerebrovascular events in those exposed to SSRIs was 135/66 335 [0.20%, 95% confidence interval (CI) 0.17–0.24], whereas the proportion of cerebrovascular accidents in those exposed to tricyclic antidepressants (TCAs) was 28/18 620 (0.15%, 95% CI 0.09–0.21). After background group differences were controlled for, exposure to SSRIs did not increase the risk of accidents (adjusted odds ratio 1.31, 95% CI 0.87–1.97). Although the risk of cerebrovascular accidents is a rare but serious event that should carefully be monitored during antidepressant therapy, this study indicated an absence of difference between TCAs and SSRIs.