Luca Degli Esposti

Pharmacoeconomics of Antihypertensive Drug Treatment: An Analysis of How Long Patients Remain on Various Antihypertensive Therapies

The objective of the research was to perform a clinical practice‐based analysis of how long patients remain on various antihypertensive drugs. An administrative database listing of patient baseline characteristics, drug prescriptions, and hospital admissions was used. All new users of antihypertensive drugs, ≥20 years of age, receiving a first prescription for diuretics, β blockers, calcium channel blockers, angiotensin‐converting enzyme inhibitors, or angiotensin II receptor antagonists between January 1, 2000, and December 31, 2000, were included and observed for 365 days. Persistence was defined as a duration of therapy >273 days. A total of 14,062 patients were included in the study, 39.7% of whom remained on treatment (persistent patients). Persistent patients were more likely to be older, taking other drugs for concurrent disorders, hospitalized for cardiovascular diseases, and initially prescribed angiotensin II receptor antagonists. Persistent patients accounted for 80.6% of the overall cost for antihypertensive drugs. Factors associated with drug cost were age, pattern of persistence, number of prescribed classes, and specific medication at enrollment. Measuring persistence with treatment is needed to evaluate the appropriateness and the cost‐effectiveness of drug use.

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.

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.

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.

Pharmacoeconomic Burden of Undertreating Hypertension

AbstractMany studies have shown the importance of antihypertensive drug therapy as a factor in reducing the risk of cardiovascular morbidity and mortality, and in containing the cost of managing hypertension and its complications. Nevertheless, the evidence in clinical practice indicates about half of hypertensive patients do not receive pharmacological treatment and about half of treated patients do not achieve blood pressure level control. Undertreating hypertension is the leading cause of failure in drug therapy effectiveness and cost effectiveness.The pharmacoeconomic burden of undertreating hypertension can be defined as the clinical (number of cardiovascular events) and economic (costs of managing cardiovascular events) consequences that would have been avoided by adequate control of blood pressure levels. In the last few years, the increase in this burden and the restriction of budget constraints has raised the awareness of healthcare providers with regards to the need to achieve better performance and to improve disease management of hypertension.This review aims to present the current situation regarding the pharmacoeconomic burden of undertreating hypertension by identifying the key issues of this medical condition, defining and measuring the extent of undertreatment, defining and measuring costs associated with undertreatment, and discussing some fundamental aspects of disease management for hypertension.The pharmacoeconomic burden of undertreating hypertension appears to be an extremely important phenomenon for which there is currently only very limited adequate research. The present dearth of appropriate data can be largely attributed to the lack of epidemiological studies in clinical practice.Future studies are necessary for a more precise quantification of the therapeutic and economic impact of undertreating arterial hypertension in clinical practice (appropriateness studies) and for more precise selection of antihypertensive drugs on the basis of the different cost-effectiveness profiles detected in ‘real world’ settings (cost-effectiveness studies).

Cost-Analysis of Relapsing-Remitting Multiple Sclerosis in Italy after the Introduction of New Disease-Modifying Agents

Background and objectiveDuring the last decade, several agents have proven to be effective in the treatment of relapsing-remitting multiple sclerosis (RRMS), for example interferon-β (IFNβ) and glatiramer acetate. This study aimed to perform a cost-analysis of the treatment of patients with RRMS in Italy after the introduction of these new agents.Study designThis was a retrospective observational study with systematic patient inclusion.Methods and resultsData gathered from 630 patients with confirmed RRMS over a 2-year period were evaluated. Overall, the direct cost over 2 years reached €11 073 100 thousand, corresponding to a per-patient cost of €17 576 (year of costing, 2001). The cost of disease-modifying agents represented approximately 77% of the total expenditure. IFNβ accounted for 94% of the expense of disease-modifying agents, corresponding to a 2-year cost per patient of €20 223. Although glatiramer acetate and immunoglobulins were also associated with a high level of expense, these were prescribed in only 3.8% and 1.1% of patients, respectively. Using regression analyses, IFNβ therapy, disability, number of days spent in hospital per year and the frequency of magnetic resonance imaging procedures were the main predictors of total costs.ConclusionBased on the results of this study, IFNβ treatment considerably modified the management of RRMS and was associated with a rise in cost of treatment per patient.

Adherence and resource use among patients treated with biologic drugs: findings from BEETLE study

Objectives Systemic administration of anti-tumor necrosis factor alpha (anti-TNF alpha) leads to an anti-inflammatory and joint protective effect in pathologies such as rheumatoid arthritis, psoriasis, and Crohn’s disease. The aim of this study was to assess adherence to therapy, persistence in treatment (no switches or interruptions), and consumption of care resources (drugs, outpatient services, hospitalizations). Methods We conducted an observational retrospective cohort analysis using the administrative databases of five local health units. Patients filling at least one prescription for anti-TNF alpha between January 1, 2009 and December 31, 2011 were included and followed up for 1 year. Patients were defined as adherent if >80% of the follow-up period was covered by drugs dispensation. Results A total of 1,219 patients were analyzed (mean age 49.6±14.6, male 47%). Among enrolled patients, 36% were affected by rheumatoid arthritis, and 31% and 10% were affected by psoriasis and Crohn’s disease, respectively; other indications remained below these percentages. Thirty-four percent of patients (420) were treated with adalimumab, 51% (615) with etanercept, and 15% (184) with infliximab. Among the 94% of patients who did not switch, those treated with infliximab had a higher rate of adherence across all indications (51% overall) when compared to that observed in patients treated with etanercept (27%) or adalimumab (23%). The mean annual nonpharmacological expenditure for each patient in analysis was €988 for adherent and €1,255 for nonadherent patients. Infliximab was associated with the lowest cost for all indications as determined by the multivariate generalized linear model. Conclusions Patients treated with infliximab were associated with higher adherence and persistence in treatment and lower costs, as compared to those treated with adalimumab or etanercept.

How many hypertensive patients can be controlled in “real life”: an improvement strategy in primary care

BackgroundIt is well known that hypertension control is non-satisfactory, but it is not clear how many hypertensive patients can be controlled in real life. We addressed this question implementing a simple, multifaceted improvement strategy in family practice.MethodsEighteen General Practitioner (GPs) agreed upon a simple improvement strategy including: 1) the use of occasional direct/indirect contacts (prescription refilling) to decrease missing blood pressure (BP) recording, and to increase therapeutic adherence, 2) the use of home BP measurements in non-controlled patients, 3) the addition of a new drug in non-controlled, but adequately adherent patients. Results were assessed after one year by automatic data extraction from the clinical records of all hypertensive subjects.ResultsThe patients with a diagnosis of hypertension increased from 6.309 (age 58.5 +/- 12.4; M 45.5%) to 6.717 (age 58.6 +/- 12.9; M 45.7%): prevalence 25.3% to 27.0%. The BP recording increased: 4,305 patients (68.2%) vs 4,948 patients (78.4%) (+ 10.2%, ci 9.4%-10.9%; p < 0.001), as well as the BP control: 3,203 (50.8% of all the diagnosed hypertensive patients and 74.4% of the subjects with recorded BP value) vs 4,043 (64.1% of all the diagnosed hypertensive patients and 81.7% of the subjects with recorded BP value) (+ 13.3%, ci 12.5%-14.2%; p < 0.001 and + 7.3%, ci 6.7%-8.0%; p < 0.001).ConclusionsAlmost 82% of hypertensive subjects who contact their doctors can be easily controlled. Most non-controlled patients simply don’t see their GPs; in almost all the remaining non-controlled patients GPs fail to increase drug therapy. A further improvement is therefore possible.

Pharmaco-utilisation and related costs of drugs used to treat schizophrenia and bipolar disorder in Italy: the IBIS study

BackgroundSchizophrenia and bipolar disorder (BD) are psychiatric diseases that are commonly managed with antipsychotics. Treatment pathways are highly variable and no universal treatment guidelines are available. The primary objective of the Italian Burden of Illness in Schizophrenia and BD (IBIS) study was to describe pharmaco-utilisation of antipsychotic treatments and characteristics of patients affected by schizophrenia or BD. A secondary objective was to describe costs of illness for patients with schizophrenia or BD.MethodsIBIS was a multicentre, real-world, retrospective, observational cohort study based on data obtained from administrative databases of 16 Local Health Units in Italy (~7.5 million individuals). Patients with schizophrenia or BD ≥18 years of age treated with antipsychotics between 1 January 2008 and 31 December 2009 were included in the primary analysis. Pharmaco-utilisation data were gathered over a follow-up period of 12 months.ResultsPatients with schizophrenia and BD received a wide variety of antipsychotic medications. The proportion of patients on antipsychotic monotherapy was 68% in patients with schizophrenia and 70% in patients with BD. In patients with schizophrenia, ~1/3 of patients receiving antipsychotic monotherapy also received mood stabilisers and/or antidepressants (34.7%) compared with over half of those on antipsychotic polytherapy (52.2%). In patients with BD, use of mood stabilisers and/or antidepressants was even higher; 76.9% of patients receiving antipsychotic monotherapy also received mood stabilisers and/or antidepressants compared with 85.5% of patients on antipsychotic polytherapy. Switch therapy was more frequent in patients with BD than in patients with schizophrenia, whereas add-on therapy was more frequent in patients with schizophrenia than in patients with BD. The mean total disease-related cost per patient per annum was higher in patients with schizophrenia (€4,157) than in patients with BD (€3,301). The number and cost of hospitalisations was higher in patients with BD, whereas the number and cost of nursing home stays was higher in patients with schizophrenia.ConclusionUse of administrative databases has permitted retrieval of comprehensive information about therapeutic pathways, diagnostic history and costs in patients affected by schizophrenia or BD. A need for personalised treatment pathways has been described.Trial registrationclinicaltrials.gov: NCT01392482; first received June 29, 2011

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

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.