Real-world evidence for vitiligo using an electronic medical records database in Spain: the REVEAL-ES study.

The European prevalence of vitiligo diagnosis is 0.2%-0.8%, with country-specific and methodological differences. Although vitiligo profoundly impacts quality of life, limited studies have evaluated disease burden and treatment patterns. This real-world study describes the prevalence, incidence, characteristics, and treatment patterns of vitiligo among patients in Spain during 2015-2021. This retrospective observational study using the IQVIA Electronic Medical Records database in Spain included patients with vitiligo (International Classification of Diseases, Ninth Revision codes 709.01/374.53). Incident and prevalent cohorts comprised registered patients with vitiligo diagnoses during and before 2015-2021, respectively. Patient characteristics and treatment data were extracted. Vitiligo incidence was 0.016 (95% CI: 0.014-0.018) per 100 person-years, and prevalence was 0.19% (95% CI: 0.18%-0.19%) in 2021. Females were more affected than males (0.16% vs 0.13%, respectively). Among 1,400 incident patients, mean (SD) age was 40.7 (19.7) years; most were female (53.9%). The most common comorbidities after vitiligo diagnosis were eczema (20.8%), hypercholesterolaemia/hypertriglyceridaemia (17.9%), anxiety (10.9%), thyroid disorders (9.1%), and diabetes (6.4%). In 2021, 78.6% of prevalent patients did not receive vitiligo-related treatments. The most prescribed vitiligo-related treatments were topical calcineurin inhibitors (13.9%) and topical corticosteroids (13.0%); 11.9% had a record of psychiatric medications. This study confirms the association between vitiligo and comorbidities (e.g., eczema, thyroid disorders) and high disease burden. The prevalence in Spain in 2021 (0.19%) was within the lower band of European estimates based on surveys/medical screenings. Most patients are not receiving vitiligo-related treatment and could benefit from new, effective treatments.

Direct Medical Costs of Four Vaccine-Preventable Infectious Diseases in Older Adults in Spain.

OBJECTIVE: Protection against vaccine-preventable diseases is especially relevant in older adults due to age-related decline in immunity (immunosenescence). However, adult vaccination remains a challenge with overall low coverage rates, which has an impact on both the patients who have these diseases and the health care system in terms of resource use and costs derived. This study aimed to estimate the direct economic impact of herpes zoster, pneumococcal disease, influenza and pertussis in Spanish adults 45 years and older. METHODS: Data from 2015 were extracted from two Spanish public databases: the Minimum Basic Data Set for Hospitalisations and the Clinical Database of Primary Care. Codes from the International Classification of Diseases and the International Classification of Primary Care were used to identify and classify the diseases analysed. The variables extracted and calculated were hospitalisation (cases, percentage, length of stay, costs, mortality), primary care (cases, percentage, costs) and referrals (cases, percentage, costs). Results were presented for the age groups 45-64 years, 65-74 years, > 74 years and all ages. RESULTS: In adults 45 years and older, total costs amounted to €134.1 million in 2015 (i.e. 63.9% of the total direct costs for all age groups): 44.4% due to pneumococcal disease, 39.5% due to influenza, 16.0% due to herpes zoster and 0.1% due to pertussis. Hospitalisations represented 58.1% (€77.9 million) of the total costs, with 15,910 admissions, 144,752 days of hospitalisation and 1170 deaths. Primary care registered 566,556 visits with a cost of €35.0 million, and 269,186 referrals with a cost of €21.1 million. CONCLUSION: The direct economic burden of herpes zoster, pneumococcal disease, influenza and pertussis in adults 45 years and older was high in Spain, and may be underestimated as it only considered medical assistance and not other applicable direct or indirect costs. Increasing vaccination rates in adults may potentially reduce the economic burden derived from these diseases, although future cost-effectiveness analysis including other disease-related costs, vaccination costs and vaccination effectiveness would be needed.

Cost-utility analysis of influenza vaccination in a population aged 65 years or older in Spain with a high-dose vaccine versus an adjuvanted vaccine.

BACKGROUND: The normal ageing process is accompanied by immunosenescence and a progressive weakening of the immune system. High-dose inactivated influenza quadrivalent vaccine (HD-QIV) has shown greater immunogenicity, relative efficacy, and effectiveness than the standard-dose inactivated quadrivalent vaccine (SD-QIV). The aim of the study was to assess the cost-utility of an HD-QIV strategy compared with an adjuvanted trivalent inactivated vaccine (aTIV) strategy in the population above 65 years of age in Spain. METHODS: We evaluated the public health and economic benefits of alternatives by using a decision-tree model, which included influenza cases, visits to the general practitioner (GP), visits to the emergency department (ED), hospitalisations, and mortality related to influenza. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economical sources of uncertainty. RESULTS: Our results show that switching from aTIV strategy to HD-QIV would prevent 36,476 cases of influenza, 5,143 visits to GP, 1,054 visits to the ED, 9,193 episodes of hospitalisation due to influenza or pneumonia, and 357 deaths due to influenza - increasing 3,514 life-years and 3,167 quality-adjusted life-years (QALYs). Healthcare costs increase by €78,874,301, leading to an incremental cost-effectiveness ratio (ICER) of €24,353/QALY. The sensitivity analysis indicates that the results are rather robust. CONCLUSION: Our analysis shows that HD-QIV in people over 65 years of age is an influenza-prevention strategy that is at least cost-effective, if not dominant, in Spain. It reduces cases of influenza, GP visits, hospitalisations, deaths, and associated healthcare costs.

Social Restrictions versus Testing Campaigns in the COVID-19 Crisis: A Predictive Model Based on the Spanish Case.

The global COVID-19 spread has forced countries to implement non-pharmacological interventions (NPI) (i.e., mobility restrictions and testing campaigns) to preserve health systems. Spain is one of the most severely impacted countries, both clinically and economically. In an effort to support policy decision-making, we aimed to assess the impacts of different NPI on COVID-19 epidemiology, healthcare costs and Gross Domestic Product (GDP). A modified Susceptible-Exposed-Infectious-Removed epidemiological model was created to simulate the pandemic evolution. Its output was used to populate an economic model to quantify healthcare costs and GDP variation through a regression model which correlates NPI and GDP change from 42 countries. Thirteen scenarios combining different NPI were consecutively simulated in the epidemiological and economic models. Both increased testing and stringency could reduce cases, hospitalizations and deaths. While policies based on increased testing rates lead to higher healthcare costs, increased stringency is correlated with greater GDP declines, with differences of up to 4.4% points. Increased test sensitivity may lead to a reduction of cases, hospitalizations and deaths and to the implementation of pooling techniques that can increase throughput testing capacity. Alternative strategies to control COVID-19 spread entail differing economic outcomes. Decision-makers may utilize this tool to identify the most suitable strategy considering epidemiological and economic outcomes.

Cost-effectiveness analysis of laparoscopic versus open surgery in colon cancer.

BACKGROUND: Few economic evaluations have assessed laparoscopy for colon cancer. This study aimed to compare the cost-effectiveness of laparoscopic and open surgery for the treatment of colon cancer. METHOD: A cost-effectiveness analysis was performed comparing two groups of patients treated according to standard clinical practice (REDISSEC-CARESS/CCR cohort) by laparoscopic or open surgery. Data were collected from health records on clinical characteristics and resource use over 2 years after surgery. To calculate the incremental cost-effectiveness ratio, costs and quality-adjusted life years (QALYs) were obtained for each patient. Clinical heterogeneity was addressed using propensity score and joint multivariable analysis (seemingly unrelated regression) that included interactions between TNM stage, age, and surgical procedure to perform subgroup analysis. RESULTS: The sample was composed of 1591 patients, 963 who underwent laparoscopy and 628 open surgery. Using propensity score and regression analysis, we found that laparoscopy was associated with more QALYs and less resource use than open surgery (0.0163 QALYs, 95% CI 0.0114-0.0212; and - €3461, 95% CI - 3337 to - 3586). Costs were lower for laparoscopy in all subgroups. In the subgroups younger than 80 years old, utility was higher in patients who underwent laparoscopy. Nevertheless, open surgery had better outcomes in older patients in stages I-II (0.0618 QALYs) and IV (0.5090 QALYs). CONCLUSION: Overall, laparoscopy appears to be dominant, resulting in more QALYs and lower costs. Nevertheless, while laparoscopy required fewer resources in all subgroups, outcomes may be negatively affected in elderly patients, representing an opportunity for shared decision making between surgeons and patients. ClinicalTrials.gov Identifier: NCT02488161.

Cost-effectiveness analysis of quadrivalent influenza vaccine in Spain.

Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention.

Prevalence, Treatment, and Control of Hypercholesterolemia in High Cardiovascular Risk Patients: Evidences from a Systematic Literature Review in Spain.

INTRODUCTION: Cardiovascular diseases (CVDs) represent a major Public Health burden. High serum cholesterol levels have been linked to major CV risk. The objectives of this study were to review the epidemiology of hypercholesterolemia in high risk CV patients from Spain, by assessing its prevalence, the proportion of diagnosed patients undergoing pharmacological treatment and the degree of attained lipid control. METHODS: A systematic literature review was carried out using Medline and two Spanish databases. Manuscripts containing information on hypercholesterolemia in several high CV risk groups [diabetes mellitus (DM), Systematic COronary Risk Evaluation (SCORE) risk >5, or documented CVD], published between January 2010 and October 2014, were included. RESULTS: Of the 1947 published references initially retrieved, a full-text review was done on 264 manuscripts and 120 were finally included. Prevalence of hypercholesterolemia ranged from 50 to 84% in diabetics, 30-60% in patients with DM or elevated SCORE risk, 64-74% with coronary heart disease, 40-70% in stroke patients, and 60-80% in those with peripheral artery disease. Despite the finding that most of them were on pharmacological treatment, acceptable control of serum lipids was very variable, ranging from 15% to 65%. Among those with heterozygous familial hypercholesterolemia, 95-100% received treatment but less than 50% achieved their therapeutic goals. CONCLUSIONS: An elevated prevalence of hypercholesterolemia can be found in targeted groups at high CV risk. Although most patients are receiving pharmacological treatment, rates of lipid control continue to be low, both in primary and secondary prevention.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography accuracy in the staging of non-small cell lung cancer: review and cost-effectiveness.

Aim of the performed clinical study was to compare the accuracy and cost-effectiveness of PET/CT in the staging of non-small cell lung cancer (NSCLC). Material and Methods. Cross-sectional and prospective study including 103 patients with histologically confirmed NSCLC. All patients were examined using PET/CT with intravenous contrast medium. Those with disease stage ≤IIB underwent surgery (n = 40). Disease stage was confirmed based on histology results, which were compared with those of PET/CT and positron emission tomography (PET) and computed tomography (CT) separately. 63 patients classified with ≥IIIA disease stage by PET/CT did not undergo surgery. The cost-effectiveness of PET/CT for disease classification was examined using a decision tree analysis. Results. Compared with histology, the accuracy of PET/CT for disease staging has a positive predictive value of 80%, a negative predictive value of 95%, a sensitivity of 94%, and a specificity of 82%. For PET alone, these values are 53%, 66%, 60%, and 50%, whereas for CT alone they are 68%, 86%, 76%, and 72%, respectively. Incremental cost-effectiveness of PET/CT over CT alone was €17,412 quality-adjusted life-year (QALY). Conclusion. In our clinical study, PET/CT using intravenous contrast medium was an accurate and cost-effective method for staging of patients with NSCLC.

Employment status and indirect costs in patients with renal failure: differences between different modalities of renal replacement therapy.

BACKGROUND: There are evidences of a different employment status between patients undergoing different modalities of renal replacement therapy (RRT). OBJECTIVES: The present study aims to compare the indirect costs associated to morbidity in the following RRT alternatives: hemodialysis in a specialized center (HD), automated peritoneal dialysis (APD), continuous ambulatory dialysis (CAPD), and renal transplant (TX). METHODS: An analysis on indirect costs was implemented following the Human Capital Theory. In total, 243 patients in working age were included (32 CAPD, 46 APD, 83 HD and 82 TX) from 8 hospitals. The potentially productive years of life lost (PPYL), the costs of lost labor productivity (LLPc) for the year 2009 and the total cost of PPYL (PPYLtc) until age of retirement were estimated. All the estimations were adjusted by age, sex rates. Non-parametric analysis (a bootstrap confidence intervals of differences in costs calculated following the simple bias-corrected percentile method -1,000 estimates-) was computed to highlight differences in costs. RESULTS: No significant differences were found in age or sex between groups. LLPc-2009- in HD (6,547€-95% CI: 5,727€-7,366€) was significantly higher (p<.001) than TX (5,079€-95% CI: 4,127€-6,030€) or APD (4,359€-95% CI: 3,064€-5,655€) but not CAPD (5,785€-95% CI: 4,302€-7,269€). PPYLs were: HD 12.58 years-95% CI: 10.42-14.73; TX 10.05-95% CI: 7.45-12.65; APD 6.09-95% CI: 3.43-8.74; CAPD 10.69-95% CI: 6.14-15.23. PPYLtc was higher in HD than in TX, APD or CAPD in all the provided scenarios. CONCLUSIONS: TX and, specially, APD are the modalities of RRT with the lowest impact on indirect costs due to morbidity showing higher rates of employment than HD and requiring less disability benefits.

Cost-effectiveness analysis of 64-slice computed tomography vs. cardiac catheterization to rule out coronary artery disease before non-coronary cardiovascular surgery.

AIMS: To explore the cost-effectiveness of two alternative strategies to rule out significant coronary artery disease (CAD) in the pre-operative evaluation of non-coronary cardiovascular surgery: initial pre-operative coronary 64-slice computed tomography angiography (CCTA) vs. invasive coronary angiography (ICA). METHODS AND RESULTS: These diagnostic strategies are compared from the clinical and payee's perspective, on the basis of the results of four European studies including 490 patients, by an analytic model of a decision tree in terms of the cost-effectiveness as the percentage of catheterizations, complications, and deaths avoided. These studies show that 71.2% of the ICA and 3.56% of the post-ICA complications could have been avoided by an initial pre-operative CCTA with a saving of €411/patient. The sensitivity analysis did not find relevant differences in terms of the cost-effectiveness when we established the indication of ICA vs. CCTA in relation to the amount of coronary calcium and when ICA was always performed by radial access. However, the lack of team experience in CCTA increased the economical and biological cost due to involving an ICA and the exposure to double ionizing radiation sources. CONCLUSION: In experienced groups, the diagnostic strategy with initial pre-operative CCTA is better than the strategy with initial ICA because it is capable of ruling out significant CAD avoiding ICA and post-ICA morbidity-mortality, with an important saving in the cost of the diagnostic process.

Influence of size and complexity of the hospitals in an enhanced recovery programme for colorectal resection.

PURPOSE: The aim of this study was to see whether the application of the enhanced recovery programme for colorectal resection improves the results and, in turn, the influence of complexity and size of the hospitals in applying this and its results. METHODS: A multi-centric prospective study was controlled with a retrospective group. The prospective operation group included 300 patients with elective colorectal resection due to cancer. The centres were divided depending on size and complexity in large reference centres (group 1) and area and basic general hospitals (group 2). The retrospective control group included 201 patients with the same characteristics attended before the application of the programme. Completion of categories of the protocol, complications, perioperative mortality and stay in hospital were recorded. RESULTS: The introduction of the programme achieved a reduction in mortality (1 vs. 4 %), morbidity (26 vs. 39 %) and preoperative (<24 h vs. 3 days) and postoperative (7 vs. 11 days) stays (p < 0.01). There was greater fulfilment of protocol in group 2 with the mean number of items completed at 8.46 and 60 % completed compared with the hospitals in group 1 (7.70 completed items and 55 % completion). The size of the hospital had no relation to the rate of complications (21.3 vs. 26.5 %). In smaller sized and less complex hospitals, the average length of stay was 1.88 days less than in those of greater size (6.45 vs. 8.33 days). CONCLUSION: Patients treated according to an enhanced recovery programme develop significantly fewer complications and have a shorter hospital stay. The carrying out of protocol is greater in smaller and less complex hospitals and is directly related to a shorter stay in hospital.

Esophageal Doppler monitoring during colorectal resection offers cost-effective improvement of hemodynamic control.

OBJECTIVES: Hemodynamic control can improve the outcome of surgery. Esophageal Doppler monitoring measures blood flow by ultrasound waves. This work investigates the cost-effectiveness of this procedure during colorectal resection. METHODS: Meta-analyses of randomized controlled trials of esophageal Doppler monitoring used in colorectal resection were conducted to help determine its cost-effectiveness. An analytical decision model was used to compare the cost-effectiveness of strategies involving conventional clinical assessment with or without the measurement of central venous pressure, with or without esophageal Doppler monitoring. Avoided mortality and avoided major complications were used as measures of clinical effectiveness. RESULTS: In the meta-analyses comparing conventional clinical assessment plus central venous pressure monitoring with or without esophageal Doppler monitoring, statistically significant differences in total and major complications favoring the use of Doppler were found. No differences were seen in mortality. The use of esophageal Doppler monitoring was associated with lower costs, mainly due to fewer complications, shorter hospital stays and shorter surgery times. CONCLUSIONS: Although the information regarding the clinical effectiveness of esophageal Doppler monitoring in colorectal resection is limited, strategies including this form of blood flow monitoring may be cost-effective. Further comparisons of Doppler monitoring against other hemodynamic monitoring systems should be undertaken.

Economic assessment of cardiac resynchronization therapy.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization devices have been shown to be effective in treating heart failure. They reduce overall mortality, heart failure mortality and hospitalizations due to heart failure. The aim of this study was to compare the cost-effectiveness of cardiac resynchronization therapy (CRT) with that of optimal drug therapy (ODT) by carrying out an economic assessment in the Spanish healthcare setting. METHODS: An existing model was adapted for use in the Spanish healthcare setting. The effectiveness of cardiac resynchronization therapy was determined from published systematic reviews. The costs of the various interventions were determined using a range of Spanish data sources. The model adopted the perspective of the public health system and the time horizon considered was the remainder of the patient's life. The outcome variables were life-years gained and quality-adjusted life-years (QALYs) gained. RESULTS: Overall, ODT, CRT and CRT with a defibrillator resulted in gains of 2.11, 2.8 and 3.19 QALYs, respectively, at a cost of €11,722, €31,629 and €52,592, respectively. Consequently, each QALY gained with CRT relative to ODT involved the consumption of €28,612 of additional resources. Similarly, the use of CRT with a defibrillator cost an additional €53,547 per QALY relative to CRT without a defibrillator. CONCLUSIONS: The use of CRT without a defibrillator could be a cost-effective alternative to ODT for treating heart failure in a carefully selected group of patients. The study results were sensitive to uncertainties in many of the variables used in the model.

Evaluación económica de la terapia de resincronización cardiaca / Economic assessment of cardiac resynchronization therapy

Introducción y objetivos. La terapia de resincronización cardiaca es un tratamiento de eficacia demostrada para la insuficiencia cardiaca y reduce el número de hospitalizaciones y la mortalidad por progresión de la insuficiencia y total. El objetivo de nuestro trabajo es determinar la eficiencia de la terapia de resincronización cardiaca comparada con la terapia farmacológica mediante una evaluación económica adaptada a nuestro entorno sanitario. Métodos. Se realiza la adaptación al ámbito sanitario español de un modelo previamente existente. Las fuentes de efectividad utilizadas son revisiones sistemáticas de la literatura publicadas. Los costes de las distintas intervenciones se determinan de acuerdo con diversas fuentes de datos españolas. Se utiliza la perspectiva del sistema sanitario; como horizonte temporal, el resto de vida de los pacientes, y como variables de resultado, años de vida y años de vida ajustados por calidad (AVAC). Resultados. El tratamiento farmacológico, la resincronización y resincronización + desfibrilador alcanzaron 2,11, 2,8 y 3,19 AVAC, a un coste de 11.722, 31.629 y 52.592 euros respectivamente. Cada AVAC obtenido con resincronización frente a medicación requiere el uso de 28.612 euros de recursos adicionales. De modo análogo, la resincronización con desfibrilador cuesta 53.547 euros/ AVAC respecto a la resincronización sin desfibrilador. Conclusiones. La terapia de resincronización cardiaca sin desfibrilador puede ser una opción de tratamiento coste-efectiva para el grupo de pacientes adecuadamente seleccionados, comparada con la terapia farmacológica óptima. Este resultado es sensible por la incertidumbre en numerosas variables del modelo (AU)

Introduction and objectives. Cardiac resynchronization devices have been shown to be effective in treating heart failure. They reduce overall mortality, heart failure mortality and hospitalizations due to heart failure. The aim of this study was to compare the cost-effectiveness of cardiac resynchronization therapy (CRT) with that of optimal drug therapy (ODT) by carrying out an economic assessment in the Spanish healthcare setting. Methods. An existing model was adapted for use in the Spanish healthcare setting. The effectiveness of cardiac resynchronization therapy was determined from published systematic reviews. The costs of the various interventions were determined using a range of Spanish data sources. The model adopted the perspective of the public health system and the time horizon considered was the remainder of the patient’s life. The outcome variables were life-years gained and quality-adjusted life-years (QALYs) gained. Results. Overall, ODT, CRT and CRT with a defibrillator resulted in gains of 2.11, 2.8 and 3.19 QALYs, respectively, at a cost of € 11,722, € 31,629 and € 52,592, respectively. Consequently, each QALY gained with CRT relative to ODT involved the consumption of € 28,612 of additional resources. Similarly, the use of CRT with a defibrillator cost an additional € 53,547 per QALY relative to CRT without a defibrillator. Conclusions. The use of CRT without a defibrillator could be a cost-effective alternative to ODT for treating heart failure in a carefully selected group of patients. The study results were sensitive to uncertainties in many of the variables used in the model (AU)

Laparoscopic hysterectomy in the treatment of endometrial cancer: a systematic review.

We sought to compare the safety and efficacy of laparoscopic hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy and open surgery in women with endometrial cancer. A systematic review of the literature was undertaken. Bibliographic searches of the Health Technology Assessment, National Health Service Economic Evaluation, DARE, Cochrane Database of Systematic Reviews, MEDLINE, Embase, Pascal Biomed, and Cinahl databases were made. This study sought to include systematic reviews, health technology assessment reports, and randomized clinical trials comparing laparoscopic surgery (LS) with open surgery for the treatment of endometrial cancer. The quality of the included studies was assessed using a clinical trial checklist. The clinical studies finally included were 4 randomized clinical trials. The short-term results described show that LS offers advantages with respect to postoperative recovery, including reduced bleeding, a need for fewer days of intravenous fluid therapy, and a reduced need for pain killers. In addition, intraoperative and postoperative complications were fewer among those who underwent LS in all the studies consulted. The mean hospital stay of those who underwent LS was 3 to 4 days shorter, and they returned to normal activity sooner. The number of lymph glands resected was the same with both techniques. The LS was associated with a better quality of life after surgery. With respect to long-term results, no significant differences were found in relation to overall, disease-free or cause-specific survival, according to 1 study. The short-term results of LS are equivalent or better than those achieved with open surgery, whereas the long-term results obtained by both seems equivalent but more studies are needed assessing this outcome.

Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease caused by C1 inhibitor mutations. Although more than 100 mutations have been described, epidemiologic data are lacking; therefore, we developed a Spanish HAE patient registry. OBJECTIVE: To study the prevalence of HAE and the current state of diagnosis and treatment of this disease in Spain. METHODS: Epidemiologic data were obtained by direct contact with physicians who treat patients with HAE and with patients themselves. Diagnosis was evaluated by measuring C1 inhibitor levels and function, and most families also underwent genetic studies. RESULTS: We registered 444 patients (minimal prevalence, 1.09 per 100,000 inhabitants), many of whom are asymptomatic (never having symptoms) (n = 61, 13.7%). Most symptomatic patients (62.9%) receive long-term prophylaxis with attenuated androgens (80.9%) and antifibrinolytic agents (22.8%), alone or in combination, but no patients are receiving long-term prophylaxis with C1 inhibitor. There is a long delay in diagnosis (mean, 13.1 years). Nine patients underwent a tracheotomy as a consequence of a laryngeal attack, and 30 families recalled a total of 38 relatives who died of HAE, which underlines the severity of the illness. CONCLUSIONS: The detected minimal prevalence of HAE in Spain is 1.09 per 100,000 inhabitants. Because this is a rare disease and some patients may be misdiagnosed, this prevalence could be higher.