Real-World Data Analysis of Patients Affected by Immune-Mediated Thrombotic Thrombocytopenic Purpura in Italy.

Background: The therapeutic management of immune-mediated thrombotic thrombocytopenic purpura (iTTP) has recently benefited from the introduction of caplacizumab, an agent directed at the inhibition of platelet aggregation. This real-world analysis investigated the epidemiology and the demographic and clinical characteristics of iTTP patients in Italy before and after caplacizumab introduction in 2020. Methods: Hospitalized adults with iTTP were included using the administrative databases of healthcare entities covering 17 million residents. Epidemiological estimates of iTTP considered the 3-year period before and after caplacizumab introduction. After stratification by treatment with or without caplacizumab, iTTP patients were characterized for their baseline features. Results: The annual incidence before and after 2020 was estimated in the range of 4.3-5.8 cases/million and 3.6-4.6 cases/million, respectively. From 2018 to 2022, 393 patients with iTTP were included, and 42 of them were treated with caplacizumab. Caplacizumab-treated patients showed better clinical outcomes, with tendentially shorter hospital stays and lower mortality rates (no treated patients died at either 1 month or 3 months after caplacizumab treatment initiation, compared to 10.5% and 11.1% mortality rates at 1 and 3 months, respectively, of the untreated ones). Conclusions: These findings may suggest that caplacizumab advent provided clinical and survival benefits for patients with iTTP.

Estimation of patients affected by inflammatory bowel disease potentially eligible for biological treatment in a real-world setting.

BACKGROUND/AIMS: This analysis estimated the number of inflammatory bowel disease (IBD) patients presenting criteria of eligibility for biological therapies in an Italian real-world setting. METHODS: An observational analysis was performed on administrative databases of a sample of Local Health Units, covering 11.3% of the national population. Adult IBD patients (CD or UC) from 2010 to the end of data availability were included. Eligibility criteria for biologics were the following: Criterion A, steroid-refractory active disease; Criterion B, steroid-dependent patients; Criterion C, intolerance or contraindication to conventional therapies; Criterion D, severe relapsing disease; Criterion E (CD only), highly active CD disease and poor prognosis. RESULTS: Of 26,781 IBD patient identified, 18,264 (68.2%) were treated: 3,125 (11.7%) with biologics and 15,139 (56.5%) non-biotreated. Among non-biotreated, 7,651 (28.6%) met at least one eligibility criterion for biologics, with criterion B (steroid-dependence) and criterion D (relapse) as the most represented (58-27% and 56-76%, respectively). Data reportioned to the Italian population estimated 67,635 patients as potentially eligible for biologics. CONCLUSIONS: This real-world analysis showed a trend towards undertreatment with biologics in IBD patients with 28.6% being potentially eligible, suggesting that an unmet medical need still exists among the Italian general clinical practice for IBD management.

Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. METHODS AND RESULTS: Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. CONCLUSION: NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

[Pharmaco-utilization and outcomes in patients treated with oral anticoagulants from 2014 to 2015: evidences from administrative databases of the Romagna Local Health Unit]. / Farmaco-utilizzazione ed esiti clinici in pazienti trattati con farmaci anticoagulanti orali nel periodo 2014-2015: evidenze da database amministrativi dell'Azienda Sanitaria Locale Romagna.

BACKGROUND: The present study aimed at describing (i) the characteristics of non-valvular atrial fibrillation (NVAF) patients newly treated with oral anticoagulants (vitamin K antagonists [VKA] or new oral anticoagulants [NOAC]), and (ii) their persistence to treatment assigned, clinical outcomes (bleeding and thromboembolic events) and mortality. METHODS: This study was conducted using administrative databases of an Italian Local Health Unit. All adult patients (aged ≥18 years) with NVAF and naïve to VKA (warfarin) or NOAC (rivaroxaban, apixaban, dabigatran) were included between January 1, 2014 and June 30, 2015. Propensity score matching was performed to check for confounding effects. Included patients were characterized for comorbidities, CHA2DS2-VASc and HAS-BLED score, antiplatelet drug use and followed up for at least 12 months to assess persistence to treatment and incidence of clinical outcomes. RESULTS: A total of 970 NVAF patients newly treated with oral anticoagulants were included; 595 (61.3%) received VKA and 375 (38.7%) NOAC. VKA naïve patients had a lower low and intermediate score for HAS-BLED and CHA2DS2-VASc compared to NOAC patients. Overall, 80.6% of naïve NAO patients and 73.4% of naïve AVK patients were persistent to treatment. Incidence of bleeding events was slightly higher in VKA patients (3.13/100 persons year) compared to NOAC patients (2.73/100 persons years), as well as incidence of thromboembolic events (3.48/100 persons year and 2.18/100 persons year, respectively). After propensity score matching no differences were observed. CONCLUSIONS: The majority of NVAF patients newly treated with oral anticoagulants received VKA-based therapy. Incidence of bleeding and thromboembolic events was slightly higher in VKA patients compared to NOAC patients.

Insulin Glargine U100 Utilization in Patients with Type 2 Diabetes in an Italian Real-World Setting: A Retrospective Study.

BACKGROUND: This study is aimed at estimating the proportion of type 2 diabetes mellitus (T2DM) patients treated with basal insulin (insulin glargine U100) and at evaluating daily insulin dose, treatment pattern, and adherence to treatment of these patients. METHODS: Data from administrative and laboratory databases of 3 Italian Local Health Units were retrospectively collected and analyzed. All patients with a diagnosis of T2DM between 01/01/2012 and 31/12/2012 were considered, and those with at least a prescription of insulin glargine between 01/01/2013 and 31/12/2014 were included and followed up for one year. For each patient, we evaluated HbA1c levels both at baseline and during the follow-up period and the daily average dose of insulin. Medication adherence was defined by using medication possession ratio (MPR) and reported as proportion of patients with MPR ≥ 80%. RESULTS: 7,422 T2DM patients were available for the study. According to the antidiabetic medication prescribed, patients were categorized into four groups: insulin glargine only, insulin glargine plus oral glucose-lowering drugs, insulin glargine plus rapid-acting insulin, and insulin glargine plus DPP-4 inhibitors. Median daily dose of insulin among insulin glargine only patients was higher than in other groups (35 IU vs. 20 IU, p < 0.05), and a higher percentage of them achieved a target HbA1c value of less than 7.0% (53.8% vs. 30%, p < 0.001). Adherence to insulin treatment was lowest (41%) in the insulin glargine only group compared to other groups (ranging from 58.4% to 64.4%), p < 0.001. CONCLUSIONS: A large proportion of T2DM patients treated with insulin fail in achieving the glycemic target of HbA1c level < 7%, irrespective of treatment regimen; however, basal insulin only is associated with lower therapeutic unsuccess. Adherence to antidiabetes medications is also suboptimal in these patients and should be addressed to improve long-term outcomes of reducing and preventing microvascular and macrovascular complications.

Use of antiosteoporotic drugs and calcium/vitamin D in patients with fragility fractures: impact on re-fracture and mortality risk.

PURPOSE: To evaluate the impact of pharmacological treatment in osteoporosis patients with recent fracture and to assess the incidence of subsequent fracture and all-cause mortality. METHODS: This observational retrospective study was based on data from administrative databases of five Italian Local Health Units. Osteoporosis patients aged ≥ 50 years with hospitalization for vertebral or hip fracture occurring between 01/01/2011 and 31/12/2015 were included. Treatment adherence was calculated using the medication possession ratio. Multivariable proportional hazard Cox model was used to identify factors associated with time to re-fracture and all-cause mortality. RESULTS: A cohort of 3475 patients were included and 41.5% of them did not receive any specific anti-fracture treatment. Among treated patients (N = 2032), the majority (83.6%) received calcium/vitamin D supplementation. Over a mean follow-up of 3 years, the risk of subsequent fractures was 44.4% lower in treated patients compared to untreated ones (HR = 0.556, 95% CI = 0.420-0.735, p < 0.001) and 64.4% lower in those receiving calcium/vitamin D supplementation compared to osteoporosis treatment only (HR = 0.356, 95% CI = 0.237-0.533, p < 0.001). The risk of re-fracture was 77.2% lower in treated patients who were adherent to medication (HR = 0.228, 95% CI = 0.139-0.376, p < 0.001). Treated patients had 64% lower mortality risk over the follow-up compared to untreated ones (HR = 0.360, 95% CI = 0.310-0.418, p < 0.001). CONCLUSIONS: A consistent proportion of osteoporosis patients did not receive specific treatment after a fracture, showing poor adherence to national guidelines on osteoporosis treatment. Osteoporosis drug treatment, and to a greater extent in combination with calcium/vitamin D, and adherence were correlated with lower risk of both re-fracture and all-cause mortality.

Patient characteristics and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban or vitamin K antagonists: real-world evidence from Italian administrative databases.

AIM: This study aimed to evaluate the risk of major bleeding among two cohorts of nonvalvular atrial fibrillation patients newly initiating a vitamin K antagonist (VKA) or apixaban in a real-world setting in Italy. PATIENTS & METHODS: A retrospective study using a large administrative database of Italian local health units was performed, using data from ten local health units and patients were included from the date of new initiation of apixaban or VKAs from January 2012 to June 2015. RESULTS: Risk of major bleeding was calculated using an adjusted Cox regression model. Compared with VKA, apixaban had a significantly lower risk of major bleeding (hazard ratio = 0.44 [95% CI: 0.12-0.97]). CONCLUSION: In this analysis, apixaban was associated with a lower risk of major bleeding compared with VKA.

Intraclass differences in the risk of hospitalization for heart failure among patients with type 2 diabetes initiating a dipeptidyl peptidase-4 inhibitor or a sulphonylurea: Results from the OsMed Health-DB registry.

AIMS: To re-analyse data from a previous retrospective study on 127 555 patients, in which we showed that dipeptidyl peptidase-4 (DPP-4) inhibitor therapy was associated with a lower risk of hospitalization for HF (HHF) than sulphonylurea (SU) therapy, in order to evaluate intraclass differences among DPP-4 inhibitors and SUs. METHODS: We included patients with type 2 diabetes (T2D) initiating DPP-4 inhibitor or SU therapy, alone or in combination with metformin. Patients undergoing intraclass switch, those with a previous HHF, those receiving insulin treatment, and those with <6 months observation were excluded. We calculated the incidence of first and total HHF events/1000 person-years. Cox proportional hazard and Poisson multiple regression models, as well as propensity-score matching, were used to account for baseline confounders. RESULTS: The analysis included 17 615 DPP-4 inhibitor users (60.1% sitagliptin; 27.0% vildagliptin; 12.9% saxagliptin) and 86 734 SU users (37.5% glibenclamide; 34.6% glimepiride; 27.9% gliclazide). No intraclass difference in the incidence rate of first and total HHF events was noted among the 3 DPP-4 inhibitors or among the 3 SUs. Multivariable adjustments for baseline confounders or propensity-score matching did not change the results. In addition, no intraclass difference in HHF risk was observed in patients at high compared with low cardiovascular risk. CONCLUSIONS: In a cohort of patients with T2D taken from approximately one-third of the Italian population, no intraclass difference was noted for DPP-4 inhibitor and SU therapy with regard to HHF risk.

Pharmacoutilization of epoetins in naïve patients with hematological malignancies in an unselected Italian population under clinical practice setting: a comparative analysis between originator and biosimilars.

AIM: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in naïve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. METHODS: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (ΔHb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. RESULTS: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean ± standard deviation (SD) age was 62.5±14.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8±11.8 years). The mean ± SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6±1.1 g/dL) compared to those who started with a reference product (10.1±2.1 g/dL). No significant differences in ΔHb were observed between biosimilar and originator groups during the followup period. The mean ± SD cost per patient was €667.98±573.93 and €340.85±235.73 for the reference product and biosimilar users, respectively (p=0.065). CONCLUSION: Our study showed that the use of biosimilar products might contribute to controlling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice.

Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database.

AIMS: Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. METHODS AND RESULTS: We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). CONCLUSION: In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas.

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.

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.

Rate of control of LDL cholesterol and incident hypertension requiring antihypertensive treatment in hypercholesterolemic subjects in daily clinical practice.

INTRODUCTION: Preliminary evidence suggests that hypercholesterolemia is associated to an increased risk to develop hypertension. We aimed at evaluating the association between low-density lipoprotein cholesterol (LDL-C) level and incidence of new onset of hypertension in a large population sample. MATERIALS AND METHODS: A population-based cohort of 20,074 subjects with at least one LDL-C measurement between July 2006 and June 2007 and free of antihypertensive treatment (AHT) at baseline was followed from the LDL-C date until death or 31 December 2009. RESULTS: During the follow-up, 10.7% of patients with LDL-C < 130 mg/dL, 13.2% of patients with LDL-C between 130 and 159 mg/dL, 12.2% of patients with LDL-C between 160 and 189 mg/dL, and 13.9% of patients with LDL-C ≥ 190 mg/dL had new-onset hypertension requiring the initiation of AHT. Compared with the LDL-C < 130 mg/dL group, the hazard ratio (HR) of initiation of AHT increased among those with LDL-C level between 130 and 159 mg/dL (HR 1.23; 95% CI: 1.08-1.40), those with LDL-C level between 160 and 189 mg/dL (HR 1.24; 95% CI: 1.01-1.51), and those with LDL-C ≥ 190 mg/dL (HR 1.45; 95% CI: 1.11-1.89). CONCLUSION: A better control of cholesterolemia seems to be associated to a lower incidence of new-onset of hypertension requiring AHT in a large cohort of general population.

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.

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.

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.

Cost offset of lipid-lowering drugs for primary and secondary prevention of cardiovascular disease.

This review aims to perform an adherence-based pharmacoeconomic evaluation of patients receiving statin therapy. A population-based study was performed. All patients receiving statins between January 1996 and December 1999 were included in the study. Both prescriptions for statins and cardiovascular events recorded from enrolment to December 2000 were considered. A total of 18,596 patients were included in the study. The positive cost offset of treatment was demonstrated (euro 30.70 for cardiovascular events avoided per euro 100 allocated for statin therapy). The increasing of the percent cost offset was found to be related to older age, male gender and secondary prevention. This study underlined low rates of adherence to statin therapy, thus many patients may receive no or limited benefits from pharmacologic treatment.

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.