Health and economic impact of dapagliflozin for type 2 diabetes patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian general practitioners setting: a budget impact analysis.

AIM: In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting. METHODS: A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact. RESULTS: The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305€: 14,521,464€ in the first year, 33,007,064€ in the second and 55,163,777€ in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results. CONCLUSIONS: The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease.

The Value of Tucatinib in Metastatic HER2-Positive Breast Cancer Patients: An Italian Cost-Effectiveness Analysis.

BACKGROUND: This study was aimed at estimating the appropriate price of tucatinib plus trastuzumab and capecitabine (TXC), as third-line treatment, in HER2+ breast cancer (BC) patients from the Italian National Health System (NHS) perspective. METHODS: A partitioned survival model with three mutually exclusive health states (i.e., progression-free survival (PFS), progressive disease (PD), and death) was used to estimate the price of tucatinib vs trastuzumab emtansine (TDM-1), considering a willingness to pay (WTP) of 60,000 EUR. Data from the HER2CLIMB trial, the Italian population, and the literature were used as input. The model also estimated the total costs and the life-years (LY) of TXC and TDM1. Deterministic and probabilistic (PSA) sensitivity analyses were conducted to evaluate the robustness of the model. RESULTS: In the base case scenario, the appropriate price of tucatinib was 4828.44 EUR per cycle. The TXC resulted in +0.28 LYs and +16,628 EUR compared with TDM-1. Results were mainly sensitive to therapy intensity variation. In PSA analysis, TXC resulted cost-effective in 53% of the simulations. Assuming a WTP ranging 20,000-80,000 EUR, the tucatinib price ranged from 4090.60 to 5197.41 EUR. CONCLUSIONS: This study estimated the appropriate price for tucatinib according to different WTP in order to help healthcare decision makers to better understand the treatment value.

Trends in cardiovascular diseases burden and vascular risk factors in Italy: The Global Burden of Disease study 1990-2017.

AIMS: An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries. METHODS: All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries. RESULTS: Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function. CONCLUSIONS: Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.

Costs and effects of cardiovascular risk reclassification using the ankle-brachial index (ABI) in addition to the Framingham risk scoring in women.

BACKGROUND AND AIMS: Ankle brachial index (ABI) is a simple and cheap parameter to assess the presence of atherosclerosis. It could also help correctly reclassify the cardiovascular risk when added to the Framingham risk score (FRS). Recent evidence has demonstrated improvement in prediction performance of ABI when added to FRS, particularly in women. However, no studies have been published yet evaluating the cost-effectiveness of this approach. This study attempts to fill in this gap by assessing the cost-effectiveness of ABI measurements in primary prevention in women. METHODS: We developed a Markov model to compare two different strategies for assessing the cardiovascular risk (low, intermediate and high) among women in the general population: 1) FRS strategy, and 2) FRS + ABI strategy; and the relative impact associated with interventions for preventing CV events in intermediate and high-risk categories. RESULTS: In the base-case analysis, FRS + ABI reported an additional cost of € 110 and a gain of 0.0039 QALYs per patient, resulting in an ICER of € 27.986/QALY, when compared to FRS alone. The ICER improved to €1.641/QALY when using a lifetime horizon. The effectiveness of preventive CV disease interventions reported also a significant impact. A 32% reduction of CV events was the minimum value estimated to maintain FRS + ABI as a cost-effective strategy. CONCLUSIONS: The addition of ABI to FRS is a cost-effective approach in women classified at low and intermediate risk with FRS only. This new approach gives the possibility to reclassify and allocate them into the appropriate risk group and treatment.

Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors.

Recent evidence demonstrated that weekly prophylaxis with subcutaneous bispecific antibody (emicizumab) has shown higher efficacy in adolescent and adults patients affected by haemophilia A (HA) with inhibitor, compared with patients treated on demand or on prophylaxis with bypassing agents (BPAs). However, no economic evaluations assessing the value and sustainability of emicizumab prophylaxis have been performed in Europe. This study assessed the cost-effectiveness of emicizumab prophylaxis compared with BPA prophylaxis and its possible budget impact from the Italian National Health Service (NHS) perspective. A Markov model and a budget impact model were developed to estimate the cost-effectiveness and budget impact of emicizumab prophylaxis in HA patients with inhibitors. The model was populated using treatment efficacy from clinical trials and key clinical, cost and epidemiological data retrieved through an extensive literature review. Compared with BPAs prophylaxis, emicizumab prophylaxis was found to be more effective (0.94 quality adjusted life-years) and cost saving (-€19.4/-€24.4 million per patient lifetime) in a cohort of 4-year-old patients with HA and inhibitors who failed immune tolerance induction. In the probabilistic sensitivity analysis, emicizumab prophylaxis had always 100% probability of being cost-effective at any threshold. Further, the use of emicizumab prophylaxis was associated to an overall budget reduction of €45.4 million in the next 3 years. In conclusion, the clinically effective emicizumab prophylaxis can be considered a cost-saving treatment for HA with inhibitor patients. Furthermore, emicizumab treatment is also associated to a significant reduction of the health care budget, making this new treatment a sustainable and convenient health care option for Italian NHS.

Development and Validation of a Score for Adjusting Health Care Costs in General Practice.

OBJECTIVE: To develop and validate the Italian Health Search Morbidity (HSM) Index to adjust health care costs in general practice. METHODS: The study population comprised 1,076,311 patients registered in the Health Search CSD Longitudinal Patient Database between January 1, 2008, and December 31, 2010. We randomly selected 538,254 and 538,057 patients to form the development and validation cohorts, respectively. To ensure model convergence, 5% of the aforementioned cohorts were selected randomly to create development and validation samples. The outcome was the total direct health care costs covered by the national health system. Interaction between age and sex, chronic diseases, and acute diseases were entered in a multilevel generalized linear latent mixed model with random intercepts (province of residence and general practitioner) to identify determinants associated with increased or decreased costs. The estimated coefficients were linearly combined to create the HSM Index for individual patients. The score was applied to the validation sample, and measures of predictive accuracy, explained variance, and the observed/predicted ratio were computed to evaluate the model's accuracy. RESULTS: The mean yearly cost was €414.57 per patient, and the HSM Index had a median value of 5.08 (25th-75th range 4.44-5.98). The HSM Index explained 50.17% of the variation in costs. Concerning calibration, in 80% of the population, the margin of error in the estimation of costs was around 10%. CONCLUSIONS: The HSM Index is a reliable case-mix system that could be implemented in general practice for costs adjustment. This tool should ensure fairer scrutiny of resource use and allocation of budgets among general practitioners.

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.

A national survey of the management of atrial fibrillation with antithrombotic drugs in Italian primary care.

The aims of this study were to investigate trends in the incidence of diagnosed atrial fibrillation (AF), and to identify factors associated with the prescription of antithrombotics (ATs) and to identify the persistence of patients with oral anticoagulant (OAC) treatment in primary care. Data were obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database from 2001 to 2004. The age-standardised incidence of AF was: 3.9-3.0 cases, and 3.6-3.0 cases per 1,000 person-years in males and females, respectively. During the study period, 2,016 (37.2%) patients had no prescription, 1,663 (30.7%) were prescribed an antiplatelet (AP) agent, 1,440 (26.6%) were prescribed an OAC and 301 (5.5%) had both prescriptions. The date of diagnosis (p = 0.0001) affected the likelihood of receiving an OAC. AP, but not OAC, use significantly increased with a worsening stroke risk profile using the CHADS2 risk score. Older age increased the probability (p < 0.0001) of receiving an AP, but not an OAC. Approximately 42% and 24% of patients persisted with OAC treatment at one and two years, respectively, the remainder interrupted or discontinued their treatment. Underuse and discontinuation of OAC treatment is common in incident AF patients. Risk stratification only partially influences AT management.

Different models for oral anticoagulation management may be applied provided that minimal assistance criteria are fulfilled: an Italian experience.

The efficacy of adjusted-dose oral anticoagulant therapy (OAT) in the prevention of thrombotic complications in various clinical conditions is well documented. Management of OAT requires a trained physician, an organized system of follow-up, reliable international normalized ratio monitoring, and good patient communication and education. Drug interactions with coumarins are a major cause of excessive anticoagulation and hence could be an important determinant of bleeding in patients on OAT. An analysis conducted in Toscana in 2005 found 31,221 patients persistently on OAT. During the same period, potential drug-drug interactions were detected in 11,778 of these patients (37.7%). Thus, the regional government enacted a specific law for the organization of OAT management to give all patients a minimal standard of quality of OAT. A specific educational campaign was promoted with the slogan "Written is better." Three possible models to follow individual patients were identified in relation to available resources and geographic characteristics of the living area: Anticoagulation Clinic (AC), General Practitioner (GP), or combined AC and GP management. This experience, although obtained in a limited geographic area, could help improve the efficacy and safety of OAT management.

Discontinuity and failures of therapy with bisphosphonates: joint assessment of predictors with multi-state models.

BACKGROUND: Data from a cohort of women treated with bisphosphonates were used to illustrate that multi-state models may be the useful tools of analysis where two causes of treatment failure are the ultimate outcome of interest, and the sequence of recurrent episodes of treatment starting and discontinuing is also of concern. METHODS: All the 11 863 women resident in the Italian Region of Lombardy, aged 45 years or over and who received bisphosphonates for the first time during 2003 entered into the study and were followed up until December 2005. Multi-state models with in-treatment and treatment-free periods as transient states, and fractures and gastrointestinal-related events as competing causes of failure, were fitted to the data. The effect of several covariates on transition rates between states was estimated. RESULTS: One half of the women was treated with bisphosphonates for less than 27% of the period of observation. Negative prognostic factors for treatment discontinuation were younger age and the use of alendronate at once-daily dosing, with low refill compliance during follow-up. The risk of fracture was higher for older women who experienced fracture before entry in the cohort, and for those who switched between drugs, had low refill compliance, experienced episodes of treatment discontinuation and used corticosteroids during follow-up. CONCLUSIONS: The use of multi-state models in pharmacoepidemiology provides non-biased estimates of the effect of covariates in predicting treatment discontinuation, restarting and failures. Our analyses emphasize the importance of maximising compliance in order to reduce the risks of both treatment discontinuation and fracture.

Screening of older community-dwelling people at risk for death and hospitalization: the Assistenza Socio-Sanitaria in Italia project.

OBJECTIVES: To develop and validate mortality and hospitalization prognostic tools based upon information readily available to primary care physicians (PCPs). DESIGN: Population-based cohort study. Baseline predictors were patient demographics, a seven-item questionnaire on functional status and general health, use of five or more drugs, and previous hospitalization. SETTING: Community-based study. PARTICIPANTS: Prognostic indexes were developed in 2,470 subjects and validated in 2,926 subjects, all community-dwelling, aged 65 and older, and randomly sampled from the rosters of 98 PCPs in Florence, Italy. MEASUREMENTS: Fifteen-month mortality and hospitalization. RESULTS: Two scores were derived from logistic regression models and used to stratify participants into four groups. With Model 1, based upon the seven-item questionnaire, mortality rate ranged from 0.8% in the lowest-risk group (0-1 point) to 9.4% in the highest risk group (> or = 3 points), and hospitalization rate ranged from 12.4% to 29.3%; area under the receiver operating characteristic curves (AUC) was 0.75 and 0.60, respectively. With Model 2, considering also drug use and previous hospitalization, mortality and hospitalization rates ranged from 0.3% to 8.2% and from 8.1% to 29.7%, for the lowest-risk to the highest-risk group; the AUC increased significantly only for hospitalization (0.67). CONCLUSION: Prediction of death and hospitalization in older community-dwelling people can be easily obtained with two indexes using information promptly available to PCPs. These tools might be useful for guiding clinical care and targeting interventions to reduce the need for hospital care in older persons.

Co-prescriptions with itraconazole and fluconazole as a signal for possible risk of drug-drug interactions: a four-year analysis from Italian general practice.

PURPOSE: To determine the prevalence of concomitant use of drugs potentially responsible for interactions among itraconazole and fluconazole users in general practice. METHODS: During the years 1999-2002, we obtained information from the 'Health Search Database', (HSD) an Italian general practice research database. Among a total sample of 457 672 eligible patients, we included those aged >16 years, and whose diagnoses could be classified as mycosis. Itraconazole and fluconazole users were then selected. A potentially drug-drug interaction (DDI) occurred when the use of concomitant drugs were recorded within +/-30 days from the date of the first azoles prescription. Interacting drugs were classified according to the summary of product characteristics (SPC) as provided by the Italian Pharmaceutical Repertory (REFI). RESULTS: From 18 323 cases of mycosis, we selected 4843 itraconazole and 1446 fluconazole users. Potentially interacting drugs were prescribed in 8.7% of itraconazole and 6.1% of fluconazole users. For itraconazole, calcium channel blockers were the most common interacting drugs (3.3%), followed by statins (1.7%) and clarithromycin (1.3%), whereas gestoden + ethynylestradiol (2.5%) and benzodiazepines (1.8%) resulted as the most common interacting drugs among fluconazole users. CONCLUSION: Data indicate a relevant prevalence of concomitant use of medications potentially leading to drug interactions among azoles users. Because of the wide use of these medications in general practice, they should be used with clinical monitoring in view of their known side effects as well as their potential risk for drug interaction.

Patterns of persistence with antihypertensive medications in newly diagnosed hypertensive patients in Italy: a retrospective cohort study in primary care.

OBJECTIVE: To describe patterns of persistence and related primary care costs associated with first antihypertensive treatment. DESIGN AND SETTING: Retrospective cohort study during 2000-2001, using information from 320 Italian general practitioners. PARTICIPANTS: We studied 13 303 patients with newly diagnosed hypertension, who received a first single antihypertensive prescription within 3 months after diagnosis. MAIN OUTCOME MEASURES: Persistence with first-line single treatment, categorized as follows: continuers: patients continuing the first-line medication for at least 1 year; combiners: patients receiving an additional antihypertensive drug and continuing the initial medication; switchers: patients changing from the first-line to another class of antihypertensive drug and discontinuing the initial treatment; discontinuers: patients stopping the first-line treatment without having another prescription until the end of the follow-up. Primary care costs were expressed as the cost of hypertension management per person-year of follow-up. RESULTS: In the study cohort, 19.8% were continuers, 22.1% were combiners, 15.4% were switchers, and 42.6% were discontinuers. Continuation was greatest with angiotensin II type 1 receptor blocking agents (25.2%), calcium channel blockers (23.9%) and angiotensin-converting enzyme inhibitors (23.3%). Severe hypertension [hazards ratio 1.30; 95% confidence interval (CI) 1.18 to 1.43] and severe health status (hazards ratio 1.22; 95% CI 1.15 to 1.30) increased the risk of discontinuation. The likelihood of needing an additional antihypertensive drug was associated with mild-to-severe baseline blood pressure, diabetes (hazards ratio 1.20; 95% CI 1.06 to 1.36), and familial history of cardiovascular disease (hazards ratio 1.24; 95% CI 1.10 to 1.39). Discontinuers accounted for 22.4% of the total primary care cost. Initial treatment with angiotensin II type 1 receptor blocking agents and beta-blockers resulted in incremental primary care costs of 145.2 and 144.2, respectively, compared with diuretics. Combiners and switchers increased the primary care cost by 140.1 and 11.7, compared with continuers. CONCLUSION: Persistence with first-line single antihypertensive drugs is extremely low during the first year of treatment. Potential cost saving should be possible by reducing the high frequency of discontinuation. Diuretics represent the least expensive therapeutic option, although further investigations in the long-term are needed to analyse the effects of persistence on therapeutic effectiveness and related costs.

Computerized general practice databases provide quick and cost-effective information on the prevalence of angina pectoris.

BACKGROUND: The aim of this study was to compare the prevalence of angina pectoris (AP) using self-reported information and primary care databases. METHODS: A comparison between the prevalence of AP in 730,586 subjects from the Health Search Database (HSD) and 119,799 individuals from a Health Interview Survey (HIS) was performed. The age-specific prevalence was calculated by dividing the detected cases by the total number of individuals in each age group. The age-standardized prevalence was estimated by direct standardization performed using the Italian standard population. RESULTS: The HSD reported a higher crude prevalence of AP than the HIS, both in males (1374/100,000 vs 1006/100,000) and females (1449/100,000 vs 1007/100,000). In the HSD the age-specific prevalence was lower for patients aged <65 years, whilst higher estimates were reported for older patients. Age standardization slightly reduced the prevalence in both samples, although the HSD always reported higher estimates. CONCLUSIONS: Prescription data from general practice databases may be a valid, simple, and cost-effective method to evaluate and serially monitor the prevalence of AP.

Exploring the variability in antibiotic prescribing profiles among paediatricians from two different areas of Italy.

We carried out a multicentre community-based study in order to describe the antibiotic therapeutic approach of paediatricians from two different areas of Italy in the treatment of respiratory tract infection (RTIs), and to assess which factors are involved in a possible variability of prescribing habits. Forty paediatricians participated in the study between October 1998 and April 1999. They had to complete a questionnaire for each therapeutic intervention resulting in an antibiotic prescription. A logistic regression model was used to identify possible predictors in choosing parenteral antibiotics for the treatment of RTIs. In 2 975 questionnaires of antibiotic treatment, RTIs represented 90.2% of the total antibiotics used. Upper respiratory tract infections were the most commonly treated diagnostic group (59.6%), followed by lower respiratory tract infections (20.4%), and middle ear infections (19.8%). Statistically significant differences between northern and southern Italy were reported in the antibiotic prescription profile and the duration of the therapy. Another marked difference was reported in the frequency of laboratory analysis requests. The logistic regression model indicated that the use of parenteral antibiotics appears significantly related to the type of infections [lower RTIs: (OR: 3.99; 95% CI: 2.49-6.37)], the geographic location [northern Italy: (OR: 0.20; 95% CI: 0.20-0.39)], and the presence of concurrent diseases (OR: 3.21; 95% CI: 1.46-7.02). The lack of adherence to clinical guidelines and the marked variability of antibiotic prescription rates between different areas of the country appear to be related to factors other than bacterial resistance, and highlight the importance of carrying out educational programmes targeted at the national level for improving the antibiotic prescription habits for the treatment of RTIs.