Therapy discontinuation or substitution in patients with cardiovascular disease, switching among different products of the same off-patent active substance: a 'real-world' retrospective cohort study.

OBJECTIVE: The present study investigated the effects of switching to different products of the same off-patent active substance (brand name or generic) on therapy discontinuation or substitution with another molecule of the same class, in patients with cardiovascular disease treated with statins and antihypertensives in a 'real-world' setting. DESIGN: A retrospective cohort study in a 'real-world' setting. SETTING: Analysis of data performed by integrating administrative databases that included approximately two million individuals who are assisted by the National Health System from three Local Health Units located in three different regions of Italy. PARTICIPANTS: All patients aged ≥18 years with at least one prescription of simvastatin, ramipril or amlodipine in the period 1 January to 31 December 2010 were included and followed up for 2 years. MAIN OUTCOME MEASURES: Prescription refills occurring during follow-up were evaluated. Frequency of discontinuation of therapy or substitution with another molecule of the same class (eg, from simvastatin to a different statin) during follow-up was identified. RESULTS: During follow-up, therapy discontinuation or substitution was found to be more frequent in patients switching to a different product of the same active substance compared with non-switching patients (11.5% vs 10.8% and 22.2% vs 20.8% (p=0.002), respectively, in the simvastatin group; 4.0% vs 3.5% and 24.6% vs 22.7% (p<0.001), respectively, in the amlodipine group). In the ramipril group, 8% of patients undertook a therapy substitution to another molecule; no trend towards a lower percentage of substitution was observed in the non-switching group, while 18% of patients discontinued treatment, with a significant difference in favour of patients not switching. These findings were partially confirmed by multivariate analysis. CONCLUSIONS: Switches among products of the same active substance are quite common in patients with cardiovascular disease. Our study suggests that switching may expose patients to a higher risk of therapy discontinuation or substitution.

Role of the Pharmacoeconomic Aspects in the Clinical Management of Hypertension.

Hypertension constitutes a significant disease burden to the society, both in terms of the health-related repercussions as well as financial costs incurred due to morbidity and the cumulative cost of drug therapy. In the real world, it would be useful to have the opportunity to consider the appropriate use of antihypertensive drugs to inform and guide clinical practice. To evaluate the adherence of drugs prescriptions in clinical practice according to predefined standards of care, a series of indicators measurable in relation to specific conditions have been developed. This work presents four indicators: the first related to the use of drugs acting on the renin-angiotensin system in patients at high cardiovascular risk; the second related to the use of angiotensin II antagonists with expired patent; the third related the occasional prescription of antihypertensive drugs; and the fourth on the adherence to treatment with antihypertensive drugs. The four indicators were measured in the OsMed database.

Clinical outcomes and health care costs combining metformin with sitagliptin or sulphonylureas or thiazolidinediones in uncontrolled type 2 diabetes patients.

OBJECTIVES: TO COMPARE CLINICAL OUTCOMES AND HEALTH CARE COSTS ACROSS THREE COHORTS OF UNCONTROLLED DIABETIC PATIENTS WHO INITIATED TREATMENT WITH ONE OF THE FOLLOWING: sulphonylureas (SU), thiazolidinediones (TZD) or sitagliptin (SITA). MATERIALS AND METHODS: We performed a retrospective study based on a linkage between administrative and laboratory databases maintained by three Italian local health units. The index period ranged from July 2008-June 2010. Patients were treatment-naïve to either SU, TZD, or SITA, but they were already treated with other oral hypoglycemic agents. Demographics and clinical characteristics were assessed at baseline. Adherence was measured by the medication possession ratio and adherent was defined as a patient with a medication possession ratio of 80% or greater. We used a Poisson regression model to estimate the risk ratios for disease-related hospitalizations that occurred during the 18-month follow-up period. The total annual costs included all the pharmacological treatments and the direct costs due to hospitalizations and outpatient services. RESULTS: We identified 928 patients treated with SU, 330 patients treated with TZD, and 83 patients treated with SITA. SITA patients were significantly younger and with fewer previous hospital discharges. The baseline mean glycated hemoglobin level was 8.1% for SU, 8.0% for TZD, and 8.3% for SITA patients. SITA-naïve patients were more adherent than the SU- and TZD-naïve patients (79.5% versus 53.2% and 62.8%, respectively; P<0.001). The SU and TZD group showed a significant increased risk of disease-related hospitalizations compared with the SITA group (the unadjusted rate was 10.42 and 7.16 per 100 person-years versus 1.64 per 100 person-years, P=0.003; compared with SU, the adjusted incidence rate ratio for SITA was 0.21, P=0.030). The total annual costs per patient were €972 for SITA, €706 for SU, and €908 for those treated with TZD. CONCLUSION: Uncontrolled diabetic patients who initiated - as a second-line therapy in addition to metformin - treatment with SITA, compared to those who initiated treatment with SU or TZD, showed a reduced risk of disease-related hospitalizations. The total annual costs per patient were not significantly different among the three groups.

Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study.

BACKGROUND: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. AIM: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. MATERIALS & METHODS: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. RESULTS: We identified a peak of association in CAMK1D gene (rs10752271, effect size -5.5 ± 0.94 mmHg, p = 1.2 × 10(-8)). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. CONCLUSION: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension.

[Administrative databases of the Local Health Unit: possible use for clinical governance of chronic kidney disease]. / Gli archivi amministrativi delle Aziende Sanitarie: possibile uso per il governo clinico della malattia renale cronica.

Nowadays a large amount of medical data are available, although they are not always homogeneous, they arise from different backgrounds and are used for different purposes. The aggregation of these data could give huge boost to the epidemiology and, in particular, to nephrology. In many parts of Italy there is the aim to reorganize the hospital health care, as well as the territorial setting. In this framework, the role of nephrology is evaluated without data to support the ongoing decisions, therefore the linkage among the data stored in the administrative and clinical databases of the Local Health Unit could contribute to the planning of nephrological (but not only) activities, in order to ensure the best cost-effectiveness possible for each different reality.

Drug adherence to olmesartan/amlodipine fixed combination in an Italian clinical practice setting.

OBJECTIVE: To investigate the criteria for prescribing a combination pill for hypertensive patients, and whether the combination pill improves medication adherence. MATERIALS AND METHODS: This was a retrospective cohort study, performed in three Italian local health units. We selected all adult subjects who received at least one prescription of antihypertensive drugs between September 1, 2011 and December 31, 2011 (the enrollment period). The date of the first antihypertensive claim was defined as the index date. For each patient, we documented the antihypertensive drug treatments and evaluated patients' adherence to treatment, which was calculated, separately, as the proportion of days covered in the two 6-month periods preceding and following the index date. Only patients treated with olmesartan and/or amlodipine as a single therapy, or as a two-pill combination in the period prior the index date were included. Changes in adherence levels were compared in subjects who moved to the fixed combination of olmesartan/amlodipine after the index date and in subjects who did not. RESULTS: A cohort of 21,008 subjects with a 6-month history of a prescription of olmesartan and amlodipine as two pills in a combination treatment, or as single-pill treatment, was obtained. Subjects treated with the two-pill combination treatment moved to the olmesartan/amlodipine fixed combination treatment more frequently than did subjects with a single-pill treatment (P<0.001). Comparing the postindex date period to the preindex date period, adherence to treatment was found to be higher in the 239 subjects who moved to the olmesartan/amlodipine fixed combination therapy (from 59.0% to 78.7%; P<0.001), than in the 20,769 subjects who did not move to the olmesartan/amlodipine fixed combination therapy (from 56.3% to 63.0%, P<0.001). CONCLUSION: The results of the present study show that the fixed combination of olmesartan/amlodipine contributes to increasing treatment adherence in subjects previously treated with a two-pill combination therapy or a single-pill therapy.

Glycemic control and diabetes-related health care costs in type 2 diabetes; retrospective analysis based on clinical and administrative databases.

BACKGROUND: Diabetes is one of the most prevalent chronic diseases, and its prevalence is predicted to increase in the next two decades. Diabetes imposes a staggering financial burden on the health care system, so information about the costs and experiences of collecting and reporting quality measures of data is vital for practices deciding whether to adopt quality improvements or monitor existing initiatives. The aim of this study was to quantify the association between health care costs and level of glycemic control in patients with type 2 diabetes using clinical and administrative databases. METHODS: A retrospective analysis using a large administrative database and a clinical registry containing laboratory results was performed. Patients were subdivided according to their glycated hemoglobin level. Multivariate analyses were used to control for differences in potential confounding factors, including age, gender, Charlson comorbidity index, presence of dyslipidemia, hypertension, or cardiovascular disease, and degree of adherence with antidiabetic drugs among the study groups. RESULTS: Of the total population of 700,000 subjects, 31,022 were identified as being diabetic (4.4% of the entire population). Of these, 21,586 met the study inclusion criteria. In total, 31.5% of patients had very poor glycemic control and 25.7% had excellent control. Over 2 years, the mean diabetes-related cost per person was: €1291.56 in patients with excellent control; €1545.99 in those with good control; €1584.07 in those with fair control; €1839.42 in those with poor control; and €1894.80 in those with very poor control. After adjustment, compared with the group having excellent control, the estimated excess cost per person associated with the groups with good control, fair control, poor control, and very poor control was €219.28, €264.65, €513.18, and €564.79, respectively. CONCLUSION: Many patients showed suboptimal glycemic control. Lower levels of glycated hemoglobin were associated with lower diabetes-related health care costs. Integration of administrative databases and a laboratory database appears to be suitable for showing that appropriate management of diabetes can help to achieve better resource allocation.

Analysis of disease patterns and cost of treatments for prevention of deep venous thrombosis after total knee or hip replacement: results from the Practice Analysis of THromboprophylaxis after Orthopaedic Surgery (PATHOS) study.

INTRODUCTION: Venous thromboembolism (VTE) is a well-known complication of total hip replacement (THR) and total knee replacement (TKR). Various drugs have been introduced in an attempt to reduce the mortality as well as the short-term and long-term morbidity associated with the development of VTE. The aim of this study was to analyze drug utilization for thromboprophylaxis and the cost of illness in real clinical practice in patients with THR or TKR. MATERIALS AND METHODS: A multicenter, retrospective, observational cohort study based on local health unit administrative databases was conducted. All patients (≥18 years old) discharged for THR/TKR procedures between January 1, 2007 and December 31, 2008 were included in the study. The date of first hospital discharge was the index date; patients were followed up for a period of 12 months. RESULTS: A total of 10,389 patients were included: 3516 males (33.8%, 69.4 ± 10.4 years) and 6873 females (66.2%, 71.7 ± 9.0 years), of which 5483 (52.8%) were discharged for THR and 4906 (47.2%) for TKR. First antithrombotic treatments after discharge were enoxaparin (3937, 37.9%), heparin (3752, 36.1%), antiplatelet agents (658, 6.3%), vitamin K antagonists (276, 2.7%), fondaparinux (136, 1.3%), combinations (185, 1.8%), and no therapy (1445, 13.9%). Overall, we observed 2347 (22.6%) treatment changes; median duration of antithrombotic treatment was 23 days (range 11-47) for THR and 22 days (range 11-46) for TKR. During the follow-up period, we observed 129 cases of VTE (120 per 10,000 patients), five post-thrombotic syndrome (4.8 per 10,000 patients), and three heparin-induced thrombocytopenia (2.9 per 10,000 patients). Median cost for both THR and TKR was €9052.00 (range €8063.00-€9084.96), with a median length of stay of 9.0 days (range 6.0-12.0).

Adherence to statin treatment and health outcomes in an Italian cohort of newly treated patients: results from an administrative database analysis.

BACKGROUND: Adherence to statin treatment is expected to be associated with health outcomes. Much of the available evidence is derived from studies conducted on selected populations (eg, Medicaid population), on specific cohorts of patients (eg, patients with diabetes mellitus or those who have experienced acute myocardial infarction [AMI]), or with respect to a single outcome (eg, only death or only AMI). OBJECTIVE: The aim of this study was to evaluate the association between adherence to statin therapy and all-cause mortality and cardiovascular morbidity (AMI and stroke) in an unselected cohort of newly treated patients. METHODS: We performed a population-based retrospective cohort study that included adult patients with a first prescription of a statin from January 1, 2004, through December 31, 2006, using data from the administrative databases of the Local Health Unit of Florence in Italy. Adherence to statin treatment was estimated as the proportion of days covered (PDC) by filled prescriptions and classified as low (PDC, 21%-40%), intermediate-low (PDC, 41%-60%), intermediate-high (PDC, 61%-80%), and high (PDC, >80%). Cases with PDC ≤20% were excluded. A Cox regression model was used to investigate the association between adherence to treatment and all-cause mortality and hospitalization for AMI or stroke. RESULTS: The cohort consisted of 19,232 patients (9823 men and 9409 women) aged 18 to 102 years (mean [SD], 66.5 [11.4] years): 20.1% had been previously hospitalized for cardiovascular events and 17.6% had been treated with hypoglycemic drugs. Adherence to statins was low in 4427 patients (23.0%), intermediate-low in 3117 (16.2%), intermediate-high in 3784 (19.7%), and high in 7904 (41.1%). Lower-adherent patients were younger and had fewer comorbidities compared with higher-adherent patients. In our multivariable analyses, high adherence was significantly associated with decreased risk of all-cause death, AMI, or stroke. Compared with low adherence (hazard ratio [HR] = 1), the risk was lower in intermediate-low adherence (HR = 0.83; 95% confidence interval [CI], 0.71-0.98; P < 0.05) and much lower in intermediate-high (HR = 0.60; 95% CI, 0.51-0.70; P < 0.001) and high adherence (HR = 0.61; 95% CI, 0.54-0.71; P < 0.001). CONCLUSIONS: In this Italian cohort of newly treated patients, suboptimal adherence to statins occurred in a substantial proportion of patients and was associated with increased risk of adverse health outcomes.

Awareness of albuminuria in an Italian population-based cohort of patients treated with hypoglycemic drugs.

BACKGROUND: Albuminuria is a powerful predictor of renal and cardiovascular outcomes in type 2 diabetes and a good indicator of the evolution of renal disease. Our aim was to obtain information concerning the identification of albuminuria as well as the utilization of antihypertensive, lipid-lowering and antiplatelet drugs in patients with diabetes. METHODS: Subjects were enrolled from individuals registered with 3 Italian local health units by querying the drugs reimbursable, hospital laboratory investigation and hospital discharge databases. The determination of albumin to creatinine ratio (ACR) throughout 2007 and 2008 was defined as the index date. Patients who received at least 2 prescriptions of hypoglycemic drugs in the 12 months before the index date were classified as diabetics. We looked also for prescriptions of antihypertensive, lipid-lowering and antiplatelet drugs. RESULTS: Among a population of 701,133 subjects, we identified 29,350 patients with diabetes (4.2% of the cohort). ACR had been determined in 5,644 diabetic subjects (19.2% of that cohort). The prevalence of determination of ACR in nontreated subjects was 16.0%, while in treated subjects, it ranged from 13.6% to 34.9% according to different schedules of treatment. Drugs acting on the renin-angiotensin system were prescribed in more then 80% of diabetics. The ratio of angiotensin receptor blockers to angiotensin-converting enzyme inhibitors regimen was 0.64 in subjects without determination of ACR, 0.88 in subjects with normal albuminuria, 1.02 in subjects with microalbuminuria and 1.43 in subjects with macroalbuminuria. CONCLUSIONS: Our methodology can easily be applied to obtain an epidemiological view of albuminuria and pharmacological treatments of diabetics in a general population.

Adherence to antihypertensive medications and health outcomes among newly treated hypertensive patients.

OBJECTIVE: To evaluate adherence to antihypertensive therapy (AHT) and the association between adherence to AHT, all-cause mortality, and cardiovascular (CV) morbidity in a large cohort of patients newly treated with antihypertensives in a clinical practice setting. METHODS: An administrative database kept by the Local Health Unit of Florence (Italy) listing patient baseline characteristics, drug prescription, and hospital admission information was used to perform a population-based retrospective study including patients newly treated with antihypertensives, ≥18 years of age, with a first prescription between January 1, 2004 and December 31, 2006. Patients using antihypertensives for secondary prevention of CV disease, occasional spot users, and patients with early CV events, were excluded from the study cohort. Adherence to AHT was calculated and classified as poor, moderate, good, and excellent. A Cox regression model was conducted to determine the association among adherence to AHT and risk of all-cause mortality, stroke, or acute myocardial infarction. RESULTS: A total of 31,306 patients, 15,031 men (48.0%), and 16,275 women (52.0%), with a mean age of 60.2 ± 14.5 years was included in the study. Adherence to AHT was poor in 8038 patients (25.7% of included patients), moderate in 4640 (14.8%), good in 5651 (18.1%), and excellent in 12,977 (41.5%). Compared with patients with poor adherence (hazard ratio [HR] = 1), the risk of all-cause death, stroke, or acute myocardial infarction was significantly lower in patients with good (HR = 0.69, P < 0.001) and excellent adherence (HR = 0.53, P < 0.001). CONCLUSIONS: These findings indicate that suboptimal adherence to AHT occurs in a substantial proportion of patients and is associated with poor health outcomes already in primary prevention of CV diseases. For health authorities, this preliminary evidence underlines the need for monitoring and improving medication adherence in clinical practice.

[Achievement of therapeutic target in subjects on statin treatment in clinical practice. Results of the STAR (Statins Target Assessment in Real practice) study]. / Raggiungimento del target terapeutico nei soggetti avviati al trattamento con statine in pratica clinica. Risultati dallo studio STAR (Statins Target Assessment in Real practice).

The primary aim of the STAR Study (Statins Target Assessment in Real practice) was to determine the LDL-cholesterol reduction and to analyse patient's and therapeutic factors associated to LDL-cholesterol target attainment in newly treated subjects with statins in an unselected population in clinical practice setting. Administrative databases (including pharmaceutical prescriptions and hospital admissions) and laboratory test databases (including LDL-cholesterol values) of five local health units, distributed in Emilia Romagna, Toscana and Umbria, were linked. A retrospective cohort study was conducted and all subjects aged > or =18 years with a first prescription for statins (newly treated subjects) between January 1st, 2007 and June 30th, 2008 were included. All statin prescriptions over a 12 months follow-up period were considered and used to calculate adherence to treatment. Baseline and follow-up LDL-cholesterol, respectively, were defined according to the nearest determination to the first prescription for statins and to the end of the follow-up period. A total of 3.232 subjects was included, 1.516 males (47%) and 1.716 females (53%), with an average age equal to 65.9 +/- 11.3 years. Among included subjects, 22.,6% had a gap to LDL-cholesterol target <10%, 30.0% between 10 and 29%, 20.7% between 30 and 49%, and 26.7% . or =50%. Among those with a gap to target > or =50%, 30-49%, and 10-29%, respectively, LDL-cholesterol target was attained by 7.1%, 41.8%, and 62.% of subjects. LDL-cholesterol target attainment was associated to gap to target, adherence with treatment, and type of statin.

Antihypertensive therapy among newly treated patients: An analysis of adherence and cost of treatment over years.

OBJECTIVE: To perform a time-trend analysis of adherence and cost of antihypertensive treatment over four years. METHODS: A population-based retrospective cohort study was conducted. We included subjects ≥18 years, and newly treated for hypertension with diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers between 01 January 2004 and 31 December 2007. One-year adherence to antihypertensive therapy was calculated and classified as low, low-intermediate, intermediate, high-intermediate, and high. The direct cost of antihypertensive medications was evaluated. RESULTS: We included data for a total of 105,512 patients. The number of newly treated subjects decreased from 27,334 in 2004 to 23,812 in 2007, as well as antihypertensive drug therapy cost which decreased from €2,654,166 in 2004 to €2,343,221 in 2007. On the other hand, in the same time frame, the percentage of adherent newly treated subjects increased from 22.9% to 28.0%. Compared with subjects initiated on angiotensin receptor blockers (odds ratio [OR] = 1), the risk of nonadherence was higher in those initiated on angiotensin-converting enzyme inhibitors (OR = 1.19), combination therapy (OR = 1.44), beta-blockers (OR = 1.56), calcium channel blockers (OR = 1.67), and diuretics (OR = 4.28). CONCLUSIONS: The findings of the present study indicate that suboptimal adherence to antihypertensive medication occurs in a substantial proportion of treated patients, and improvements in treatment adherence were obtained but are still unsatisfactory.

The relationship between body weight and drug costs: An Italian population-based study.

OBJECTIVES: This study determined the prevalence of 3 categories of body mass index (BMI)--normal weight, overweight, and obesity--in a sample of subjects from general clinical practice in Ravenna, Italy, and evaluated the impact of comorbidities associated with overweight and obesity on the costs of drug treatment from the perspective of the Italian national health system. METHODS: This was a cross-sectional study conducted in a sample of subjects aged > or =18 years from 10 general practices in the Ravenna local health unit (LHU) in 2001-2002. Subjects were invited to attend a screening visit at which weight and height were measured for determination of BMI, blood pressure was measured, and a fasting blood sample was obtained for laboratory tests. The screening examinations were conducted by 2 physicians at a dedicated practice. Normal weight, overweight, and obesity were defined as a BMI < or =24.9, between 25 and 29.9, and > or =30 kg/m2, respectively. The costs of classes of drug treatment that were reimbursable to the LHU in the 12 months before the screening examination were evaluated using the Ravenna LHU administrative databases. Drug treatments were classified as antihypertensive agents, statins, NSAIDs, gastroprotective drugs, antidiabetic agents, respiratory drugs, antiplatelet agents, antidepressants, and all other drugs. The data were analyzed by age group. RESULTS: Of the 2622 subjects in the sample, 1256 (47.9%) had a normal BMI, 918 (35.0%) were overweight, and 448 (17.1%) were obese. The prevalence of overweight and obesity increased in relation to age up to 50-59 years (P < 0.001), after which it remained stable. Overweight and obese subjects had significantly more exposure to individual and multiple drug treatments compared with subjects with normal weight (P < 0.001). By type of drug treatment, 16.7% of normal-weight subjects, 35.6% of overweight subjects, and 51.8% of obese subjects were exposed to antihypertensives; 4.1%, 8.7%, and 12.1%, respectively, to statins; 14.2%, 22.0%, and 29.0% to NSAIDs; and 1.0%, 4.7%, and 9.4% to antidiabetics. The mean annual cost of drugs was Euro 132.71 in normal-weight subjects, Euro 246.19 in overweight subjects, and Euro 335.64 in obese subjects (P < 0.001). After adjustment for differences in age distribution between the study sample and the overall population of Ravenna, the estimated excess drug costs associated with overweight and obesity in Ravenna were Euro 5,661,126.20 and Euro 6,688,099.85, respectively. CONCLUSIONS: In this study sample, the prevalence of overweight increased by approximately 10% and the prevalence of obesity increased by approximately 5% with each decade of age up to 60 years, after which it remained stable at approximately 40% and approximately 20%, respectively. Overweight and obesity were associated with increased drug exposure and costs in all age groups considered.

Underuse of lipid-lowering drugs and factors associated with poor adherence: a real practice analysis in Italy.

BACKGROUND: Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated. OBJECTIVE: To analyze the management of hypercholesterolemia in a non-experimental setting and to estimate the factors associated with poor adherence to treatment. METHODS: A longitudinal study was performed using clinical and demographic data recorded in the General Practitioners' database. The sample included all patients, aged 30 years or over, with total blood cholesterol measured between 1 January and 31 December 2000. Utilization of LLDs was defined as the standardized daily dose of the drugs purchased during the 12 months preceding the cholesterol measurement. RESULTS: The study included 4764 patients (mean age 59.4+/-14.1 years, 40.7% males). Of the subjects with a total cholesterol higher than a 6.5 mmol/l, approximately 17% were treated with LLDs. About 39% of the patients with previous atherosclerotic diseases were taking statins. Analysis of patients taking LLDs showed that 40.6% of subjects took less than half of the defined daily dose. Factors associated with poor adherence to treatment were: absence of previous atherosclerotic diseases, absence of concomitant diseases, and smoking. A total cholesterol of less than 5 mmol/l was achieved in 19.9% of patients. CONCLUSIONS: Analyzing the data contained in the general medicine database made it possible to evaluate the use of LLDs in clinical practice and to establish the need to pay greater attention to achieving the objective set by the treatment.

Global cardiovascular risk evaluation in Italy: a cross-sectional survey in general practice.

BACKGROUND: The aim of our work was to evaluate, in a general practice setting, the attitude of general practitioners in determining the individual coronary risk. METHODS: The coronary risk was determined among patients aged 30 to 74 years using the following parameters: gender, age, smoking habits, diagnosis of diabetes mellitus, systolic blood pressure, and total cholesterol. We evaluated the records of 446,331 subjects collected by 481 general practitioners working throughout Italy. RESULTS: Except for age, gender and diabetes mellitus, risk factors were largely under-recorded: blood pressure in 37.0% of the total patients, total cholesterol in 34.3%, smoking habits in 21.9%. Recording was substantially low even in patients who were prescribed with antihypertensive drugs and/or lipid-lowering drugs: blood pressure in 80.6% of the patients, total cholesterol in 69.1%, smoking habits in 46.1%. Cardiovascular risk factors were more frequently recorded as age increased and slightly more among women as compared to men. Obviously, it is possible that risk factors had been assessed but not recorded. CONCLUSIONS: Cardiovascular risk factors are substantially under-recorded among Italian general practitioners thus impairing adequate preventive treatment. A systematic, well programmed approach may theoretically lead to evaluate the majority of the target population within a few years.

Pharmacoutilization of statin therapy after acute myocardial infarction. A real practice analysis based on administrative data.

BACKGROUND: Despite randomized and controlled trials indicating continuous treatment with statin therapy as a factor in reducing morbidity and mortality after acute myocardial infarction, records reveal a high percentage of patients at risk who are either not receiving treatment or being treated inadequately. METHODS: An administrative database kept by the Local Health Unit of Ravenna and listing patient baseline characteristics, drug prescriptions and hospital admissions was used to perform: 1) an analysis of patients discharged alive from hospital each year between 1996 and 2000 with a diagnosis of acute myocardial infarction, and 2) a retrospective cohort study of drug utilization, and particularly the use of statins, year by year. All prescriptions for statins filled in the 6 months after hospital discharge were considered and used to classify patients in terms of their exposure to statin therapy and of their pharmacoutilization. RESULTS: A total of 2265 subjects were enrolled (446 in 1996, 440 in 1997, 443 in 1998, 443 in 1999, and 493 in 2000). The percentage of patients treated with statins increased each year (from 22.6% in 1996 to 43.8% in 2000) as did the percentage of adequately dosed patients (from 4.3% in 1996 to 23.9% in 2000). The overall cost of dispensed statins amounted to 10,610 euros in 1996 and 45,102 euros in 2000. The proportion of cost for statins accountable to adequately dosed patients ranged from 36.4% in 1996 to 77.4% in 2000. The average cost per adequately dosed patient ranged from 203.40 euros in 1996 to 296.00 euros in 2000 and increased year by year. CONCLUSIONS: Pharmacoutilization of statin therapy was found to be unsatisfactory in each study year. Interestingly, however, the trend indicated by the study suggests increasing percentages of patients being exposed to the treatment, and of adequately dosed patients. These results may be attributed to a greater awareness of the need for proper treatment, and may be considered as reflecting a significant improvement in drug management.

Frequency of cardiovascular events in patients treated with anti hypertensive agents: A cohort study based on claims data generated by primary care practice.

BACKGROUND: Large-scale clinical trials have shown that antihypertensive drugs reduce the risk for cardiovascular events. However, little is known about the effectiveness of these drugs in the primary care setting. OBJECTIVE: The aim of this study was to investigate the frequency of cardiovascularevents during treatment with either of 2 of the most frequently prescribed antihypertensive drugs. METHODS: This observational, longitudinal, cohort study considered the entirepopulation listed in the administrative databases of the Local Health Authority of Ravenna, Italy (356,000 residents). The demographic registry and the pharmaceutical and nosocomial databases were cross-linked to determine drug treatment, as well as the frequency of cardiovascular events on a patient-by-patient basis. Each patient aged >18 years receiving a first prescription for amlodipine or enalapril in the period between January 1, 1996, and December 31, 2000, with ≥6 months of continuous treatment with the drug was included. The follow-up period varied from 6 months to 4.5 years. RESULTS: Of the 7500 patients analyzed (4092 women and 3408 men; mean[SD] age, 68.0 [12.4] years), 2231 (29.7%) were given amlodipine and 5269 (70.3%) were given enalapril. The observed rate of cardiovascular events was higher among patients treated with amlodipine (54 per 1000 patient-years vs 46 per 1000 patient-years; P = 0.007), with a hazard ratio 17% higher compared with enalapril (95% Cl, 5.0-24.0; P = 0.007). The result was also confirmed using Cox multivariate regression analysis. The combination of enalapril plus diuretic showed the lowest risk for cardiovascular events (0.73; 95% Cl, -36.0 to -16.0; P < 0.001). CONCLUSION: This analysis showed that treatment with enalapril was associatedwith a significantly lower frequency of cardiovascular events compared with amlodipine.

Effects of introducing a clinical guideline on the cost of treating dyspeptic syndrome.

This review highlights the effects incurred on pharmacoutilization and the total expenses for dyspeptic syndrome by the introduction of a clinical guideline. A retrospective method of reading an administrative billing database in the Ravenna (Italy) local health unit was performed for all subjects who were health-assisted by ten general practitioners. They had previously developed and agreed to a clinical guideline to manage dyspeptic syndrome patients (study group) and a group of 30 self-regulating general practitioners patients (control group). Patients were classified as dyspeptic according to the presence of at least one prescription for antidyspeptic drugs during a 365-day follow-up period. The cost for drugs, hospitalizations, emergency room accesses and gastroscopies was recorded. The results showed that a total of 51,904 subjects were enrolled: 23.1% by the study general practitioners and 76.9% by the control general practitioners. The percentage of dyspeptic patients accounted for 17.6 and 15.0% in the subjects enrolled in the study and control groups. The total average cost of the dyspeptic patients was less in the study than in the control group (euro163.41 vs. 181.39; p = 0.043). This difference is mainly due to the cost of hospitalization (euro94.55 in the study and euro110.92 in the control group; p = 0.012). The significant results of the introduction of a guideline for the treatment of dyspeptic syndrome into clinical practice were an increase in the use of pharmacological treatment and a decrease in the cost of treatment per patient.

Bayesian cost-effectiveness analysis based on the persistence with antihypertensive treatment.

An observational study was performed to compare five compounds as initial therapy to evaluate the persistence with antihypertensive treatment and drug cost. Over a 1-year follow-up period on the entire population (approximately 360,000 residents) of the Ravenna Local Health Unit. The presence of five major antihypertensive agents between January 1st, and December 31st, 1997 was investigated. There were 4614 patients enrolled. The annual average cost of treatment ranged between euro 44.27 (95% confidence interval, 38.18-52.06) for patients started on atenolol to euro175.65 (150.37-205.10) for those started on losartan. Patients who began losartan showed a higher posterior probability of an effective antihypertensive treatment. On average, these patients turned to produce cost-effective treatment with an average probability of 0.70.