Assessment of the treatment effectiveness of men with mild and medium degree of erectile dysfunction.

OBJECTIVE: . Aim: To assess the effectiveness of monotherapy and complex treatment of patients with erectile dysfunction depending on its severity. PATIENTS AND METHODS: Materials and Methods: Men with moderate and mild erectile dysfunction took part in the study, who, in turn, were divided into groups, depending on the treatment, with the evaluation of the results of the International Index of Erectile Function (MIEF-15), the state of cavernous hemodynamics and the function of the vascular endothelium before and after treatment. RESULTS: Results: In patients with an average degree of severity, who received complex treatment including a course of low-energy shock wave therapy, against the background of taking sildenafil and L-arginine, the best results were obtained in the quality of erection and increased cavernous blood flow, which positively affected satisfaction with sexual intercourse and overall satisfaction. It has also been proven that the function of the endothelium was improved in patients receiving L-arginine, due to which there was a probable decrease in endothelin-1. A probable improvement of erectile function was obtained in the group of patients with a mild degree who received L-arginine, and there was no statistical difference from the indicators in the group who received sildenafil, which was confirmed by the data of dopplerography. CONCLUSION: Conclusions: Patients with an average degree of erectile dysfunction require comprehensive treatment. The use of L-arginine can be an alternative to phosphodiesterase type 5 inhibitors in the treatment of mild erectile dysfunction.

Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD. Objective: To investigate the potential therapeutic benefit of sildenafil on AD. Methods: We performed real-world patient data analysis using the MarketScan® Medicare Supplemental and the Clinformatics® databases. We conducted propensity score-stratified analyses after adjusting confounding factors (i.e., sex, age, race, and comorbidities). We used both familial and sporadic AD patient induced pluripotent stem cells (iPSC) derived neurons to evaluate the sildenafil's mechanism-of-action. Results: We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced incidence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32- 0.66) and a 30% reduced prevalence of AD in Clinformatics® (HR = 0.70, 95% CI 0.49- 1.00) compared to spironolactone. We found that sildenafil treatment reduced tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient iPSC-derived neurons. RNA-sequencing data analysis of sildenafil-treated AD patient iPSC-derived neurons reveals that sildenafil specifically target AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD. Conclusions: These real-world patient data validation and mechanistic observations from patient iPSC-derived neurons further suggested that sildenafil is a potential repurposable drug for AD. Yet, randomized clinical trials are warranted to validate the causal treatment effects of sildenafil in AD.

Intrapartum use of sildenafil citrate to prevent fetal compromise and emergency operative birth in term pregnancies in the United Kingdom and Australia: A preliminary cost-effectiveness analysis.

OBJECTIVE: To compare cost-effectiveness of oral sildenafil citrate, administered after onset of labor, with standard care to health system funders in the UK and Australia. METHODS: We conducted a modeled cost-effectiveness analysis, measuring costs and quality adjusted life years (QALYs), using a decision-analytic model covering onset of labor to 1 month post-birth. The relative risk of emergency cesarean section and operative vaginal birth was taken from a Phase 2 placebo controlled double blinded randomized control trial. RESULTS: Both options of care resulted in the same QALYs gained over the model time period (0.08). Sildenafil citrate was cost-saving compared with standard care, saving £92 per birth in the UK (AU$303 per birth in Australia). Sensitivity analyses did not identify any areas of uncertainty that stopped sildenafil citrate being cost saving compared with standard care. Threshold analysis revealed that sildenafil citrate would be cost saving up to a per birth drug or administration cost of £152.32 in the UK (AU$333.61 in Australia). CONCLUSION: Oral sildenafil citrate may be cost saving compared with standard care; however, the effects on neonatal outcomes still need to be demonstrated in large randomized trials.

Phosphodiesterase 5 Inhibitor for Pediatric Pulmonary Arterial Hypertension: A Cost-Utility Analysis.

OBJECTIVES: Despite the growing evidence of efficacy, scarce information exists regarding the cost of tadalafil to improve the functional classes of pediatric patients with pulmonary arterial hypertension. This study aims to determine the cost-utility of tadalafil compared sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. METHODS: A Markov model was developed to compare expected costs, outcomes, and quality-adjusted life-years of sildenafil and tadalafil in pediatric patients with pulmonary arterial hypertension. The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay value of US $5180. RESULTS: The mean incremental cost of tadalafil versus sildenafil is US $15 270. The 95% credible interval for the incremental cost ranges from US $28 033.65 to US $5940.86. The mean incremental benefit of tadalafil versus sildenafil is 1.00 quality-adjusted life-years (QALY). The 95% credible interval for the incremental benefit ranges from 1.88 to 0.31 QALY. The expected incremental cost per QALY is estimated at US $15 286. There is a probability less than 1% that tadalafil is more cost-effective than sildenafil at a threshold of US $5180 per QALY. Form the value of information analysis, the theoretical upper bound on the value of further research was US $9.298 for Colombia. CONCLUSION: Our economic evaluation shows that tadalafil is not cost-effective regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Ambrisentan for in pediatric pulmonary arterial hypertension: A cost-utility analysis.

INTRODUCTION: Despite the growing evidence of efficacy, little is known regarding the efficiency of ambrisentan to decrease cost and improve the functional classes of pediatric patients with pulmonary arterial hypertension. This study aims to determine the cost-utility of ambrisentan regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. METHODS: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of ambrisentan, or sildenafil in pediatric patients with pulmonary arterial hypertension. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The base-case analysis showed that compared with sildenafil, ambrisentan was associated with higher costs and higher QALYs. The expected annual cost per patient with ambrisentan was US$16,105 and with sildenafil was US$1431. The QALYs per person estimated with ambrisentan was 0.40 and for sildenafil was 0.39. The estimated improvement in quality of life and reduced costs results in an estimate of economic dominance for sildenafil over ambrisentan. CONCLUSION: Our economic evaluation shows that ambrisentan is not cost-effective regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Contemporary cost-analysis comparison of direct-to-consumer vs. traditional prescriptions of phosphodiesterase-5 inhibitors.

After a focused telehealth visit, patients can now access phosphodiesterase-5 inhibitor (PDE5 inhibitor) prescriptions through online direct-to-consumer (DTC) healthcare companies. This study seeks to quantify the cost of DTC PDE5 inhibitor treatment compared to a traditional physician visit and local pharmacy prescription. Two DTC companies, two compounding pharmacies with national reach, three online Canadian pharmacies, and sixteen American pharmacy chains were queried for prices of 90-day regimens of common PDE5 inhibitors. Prices for chains were determined using their publicly available price on GoodRx® with coupon. Cost of physician visit was determined using 2020 Center for Medicare and Medicaid Services reimbursement for a level 3 new patient visit. For sildenafil 20 mg, a physician visit and local prescription cost a low of $125.45 compared to $144.35 for compounding, $169.34 for Canadian, and $195.00 for DTC. For sildenafil 100 mg, a physician visit and local prescription cost a low of $137.16 compared to $289.35 for compounding, $200.36 for Canadian, and $900.00 for DTC. For tadalafil 5 mg, a physician visit and local prescription cost a low of $125.80 compared to $169.35 for compounding, $195.34 for Canadian, and $720.00 for DTC. For tadalafil 20 mg, a physician visit and local prescription cost a low of $161.00 compared to $289.35 for compounding, $229.00 for Canadian, and $2880.00 for DTC. Thus, local pharmacies, in conjunction with online coupons, consistently provide a markedly less-expensive option for fulfillment of PDE5 inhibitor prescriptions than online DTC services.

Ambrisentana, bosentana, iloprosta, selexipague e sildenafila para o tratamento de pacientes com hipertensão arterial pulmonar / Ambrisentan, bosentan, iloprost, selexipag and sildenafil for the treatment of patients with pulmonary arterial hypertension

INTRODUÇÃO: A Hipertensão Arterial Pulmonar (HAP) é uma doença grave e progressiva que resulta em disfunção ventricular direita e comprometimento na tolerância à atividade física, podendo levar à insuficiência cardíaca direita, incapacidade e morte prematura. Possui incidência estimada de 1,9 a 3,7 novos casos/milhão de habitantes ao ano. Atualmente, são disponíveis cinco medicamentos aprovados pela Anvisa e incorporados no Sistema Único de Saúde (SUS), que incluem antagonistas do receptor de endotelina (ERA) (ambrisentana e bosentana); inibidores da fosfodiesterase 5 (PDE5i) (sildenafila) e atuantes na via da prostaciclina (PGI2), que são os análogos da PGI2 (iloprosta). O atual Protocolo Clínico e Diretrizes Terapêuticas da Hipertensão Arterial Pulmonar informa que a avaliação da Conitec foi contrária à utilização destes fármacos em terapia combinada, por falta de estudos comprobatórios de eficácia e pelos riscos de eventos adversos potencialmente graves ainda não avaliados adequadamente. A indicação de incorporação é a terapia combinada destes medicamentos e sildenafila em alta dose, como alternativas complementares de tratamento. Assim o objetivo deste relatório foi analisar as evidências científicas disponíveis sobre eficácia, efetividade, segurança, custoefetividade e impacto orçamentário do ambris

Systematic review and cost-effectiveness of bosentan and sildenafil as therapeutic drugs for pediatric pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease in children, with significant mortality. Because of the limited research on pediatric PAH, first, systematic review of related drugs is conducted, and then economic evaluation of PAH drug treatment programs is conducted, which to provide a reference for the choice of more cost-effective treatment options. METHODS: The search includes electronic databases such as Pubmed, ScienceDirect, and Embase. Through inclusion and exclusion criteria, screen high-quality randomized controlled trials. We used TreeAge Pro 2011 software to construct the markov model, that to simulate the total medical cost and quality-adjusted life years (QALYs), and to calculate the incremental cost-effectiveness ratio. Sensitivity analysis of transfer probability, utility, and cost was carried out. RESULTS: Incorporate two studies that meet the criteria, one compared the therapeutic effects of bosentan and placebo on pediatric PAH, the other compared therapeutic effects of sildenafil and placebo on pediatric PAH, both articles were of good quality. Compared with the sildenafil group (3.38QALYs and $161,120.14), the QALY of the bosentan treatment group (3.33QALYs and $257,411.29) was reduced by 0.05, and the cost increased by $96,291.15. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for sildenafil over bosentan. This dominant result persisted probabilistic analyses. CONCLUSIONS: Based on this model, a more cost-effective treatment drug for PAH in children is sildenafil.

Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis.

Importance: Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. Objective: To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED. Data Sources: Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020. Study Selection: Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included. Data Extraction and Synthesis: Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients. Results: A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high. Conclusions and Relevance: This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.

Cost-Utility of Sildenafil for Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVE: While advanced therapies for severe persistent pulmonary hypertension of the newborn (PPHN) such as inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) are standard treatments in high-income countries, these therapies are often unavailable in resource-limited settings such as middle-income countries. However, there are small clinical trials illustrating the efficacy of sildenafil at reducing mortality in PPHN. This analysis sought to determine the cost-utility of enteral sildenafil for the treatment of severe PPHN. STUDY DESIGN: A Markov-state transition model was constructed for the two clinical approaches to compare costs, clinical outcomes, and quality of life: (1) "conventional," (2) "sildenafil." The impact of sildenafil was modeled as a relative risk modifier of the conventional strategy's mortality risk. Transitional probabilities, costs, and utility metrics were extracted from the literature. Sensitivity analyses for each model input as well as 100-patient Monte Carlo simulations were used to test the durability of the model conclusion. RESULTS: The sildenafil strategy was cost-effective for upper but not lower middle-income countries with an incremental cost-effectiveness ratio of $2,339 per quality-adjusted life year. This conclusion was durable across a wide-range of model assumptions; the sildenafil strategy only failed to meet criteria for cost-effectiveness when sildenafil therapy had a mortality relative risk efficacy of >0.89, if life expectancy in that country is <40 years, or if the lifetime forecasted costs of a survivor's life was quite high. CONCLUSION: Enteral sildenafil is a cost-effective intervention for severe PPHN for upper middle-income countries where ECMO and iNO are not available. KEY POINTS: · PPHN is a common life-threatening condition in newborns.. · Sildenafil improves survival of PPHN.. · Sildenafil is cost-effective for upper-middle income countries..

Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials.

PURPOSE: Asymptomatic or minimally symptomatic infection with COVID-19 can result in silent transmission to large numbers of individuals, resulting in expansion of the pandemic with a global increase in morbidity and mortality. New ways of screening the general population for COVID-19 are urgently needed along with novel effective prevention and treatment strategies. HYPOTHESIS: A hypothetical three-part prevention, diagnostic, and treatment approach based on an up-to-date scientific literature review for COVID-19 is proposed. Regarding diagnosis, a validated screening questionnaire and digital app for COVID-19 could help identify individuals who are at risk of transmitting the disease, as well as those at highest risk for poor clinical outcomes. Global implementation and online tracking of vital signs and scored questionnaires that are statistically validated would help health authorities properly allocate essential health care resources to test and isolate those at highest risk for transmission and poor outcomes. Second, regarding prevention, no validated protocols except for physical distancing, hand washing, and isolation exist, and recently ivermectin has been published to have anti-viral properties against COVID-19. A randomized trial of ivermectin, and/or nutraceuticals that have been published to support immune function including glutathione, vitamin C, zinc, and immunomodulatory supplements (3,6 Beta glucan) could be beneficial in preventing transmission or lessening symptomatology but requires statistical validation. Third, concerning treatment, COVID-19 induced inflammation and "cytokine storm syndrome" with hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) have resulted in extreme morbidity and mortality in those with certain comorbidities, secondary to "acute respiratory distress syndrome" (ARDS) and multiorgan dysfunction with disseminated intravascular coagulation (DIC). Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress. A randomized controlled trial of blocking NF-κB and cytokine formation using glutathione precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione with associated anti-viral effects should be performed, along with an evaluation of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been scientifically proven to lower inflammation. Since high mortality rates from sepsis induced DIC due to COVID-19 infection has also been associated with thrombotic events and elevated levels of D-dimer, randomized controlled trials of using anticoagulant therapy with heparin is urgently required. This is especially important in patients on ventilators who have met certain sepsis induced coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil also needs to be explored with or without heparin, since increased oxygen delivery to vital organs through prevention of thrombosis/pulmonary emboli along with carbonic anhydrase inhibition may help increase oxygenation and prevent adverse clinical outcomes. CONCLUSION AND IMPLICATIONS: A three-part prevention, diagnostic, and treatment plan is proposed for addressing the severe complications of COVID-19. Digital monitoring of symptoms to clinically diagnose early exposure and response to treatment; prevention with ivermectin as well as nutritional therapies that support a healthy immune response; treatment with anti-inflammatory therapies that block NF-κB and activate Nrf2 pathways, as well as novel therapies that address COVID-19 pneumonia and ARDS with DIC including anticoagulation and/or novel respiratory therapies with or without acetazolamide and sildenafil. These three broad-based interventions urgently need to be subjected to randomized, controlled trials.

Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update.

BACKGROUND: While phosphodiesterase type-5 inhibitors (PDE5Is) are highly effective for the treatment of erectile dysfunction (ED) and well tolerated, updated data on prescription patterns have been limited in real-world settings. AIM: To describe men in the United States who are prescribed PDE5Is for ED treatment and to evaluate patterns of initiation, switching, and treatment overlap. METHODS: This retrospective claims study used MarketScan Commercial and Medicare Supplement Databases from January 1, 2010, to December 31, 2015, to identify initial PDE5I claims (index date) for sildenafil, tadalafil, and/or vardenafil. Adults aged ≥18 years with ED were identified between July 1, 2010, and December 31, 2014, allowing for a 6-month preindex and 12-month follow-up period from the index date. OUTCOMES: Outcomes included patient demographics and treatment-related patterns after treatment initiation. RESULTS: A total of 106,206 identified patients met all inclusion criteria. Of these, 51,694, 40,193, and 14,319 had initial claims for sildenafil, tadalafil, and vardenafil, respectively. Mean age was 50.35 years, and comorbidities included dyslipidemia (44.17%), hypertension (43.09%), diabetes (15.32%), and depression (10.61%). More patients (48.67%) initiated on sildenafil than tadalafil (37.85%) or vardenafil (13.48%). Rate of switching was lower in the 60 days after the end of day supply of the initial prescription in the sildenafil cohort (2.71%) compared with the tadalafil (2.81%) and vardenafil (3.88%) cohorts (P < .001 for sildenafil vs tadalafil or vardenafil). Treatment overlap was lower in the sildenafil cohort (0.35%) than in the tadalafil (0.75%) and vardenafil (0.62%) groups (P < .001 for sildenafil vs tadalafil or vardenafil). CLINICAL IMPLICATIONS: These findings provide insight into updated patterns of PDE5I prescriptions in the United States and may aid in clinical decision-making. STRENGTHS & LIMITATIONS: Strengths include the large sample size, long data coverage period, and the real-world nature of the study. Limitations include the retrospective study design, use of data collected with a primary focus of claims, and lack of further details regarding reasons that drive switching. Actual rates of ED and impact on prescription patterns may be underestimated because the claims database only captured patients electing to visit a health-care provider. CONCLUSION: Among men with ED in the United States, rates of switching and treatment overlap were low for all PDE5Is but were found to be the lowest for sildenafil compared with tadalafil and vardenafil. Mulhall JP, Chopra I, Patel D, et al. Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update. J Sex Med 2020;17:941-948.

A Review of Economic Evaluations of Erectile Dysfunction Therapies.

INTRODUCTION: Erectile dysfunction (ED) is a common and costly urologic condition with increasing prevalence as men age. Cost-effectiveness of ED therapies and whether cost-effectiveness varies for different populations of men remains underexplored. AIM: To review and summarize available published data on the economic evaluation of ED therapies and to identify gaps in the literature that still need to be addressed. METHODS: All relevant peer-reviewed publications and conference abstracts were reviewed and incorporated. RESULTS: There are a number of medical and surgical treatment options available for ED. The economic evaluation of phosphodiesterase-5 inhibitors, particularly sildenafil, has been well described. However, minimal research has been conducted to assess the cost-effectiveness of intracavernosal injections, intraurethral suppositories, penile prosthesis surgery, vacuum erection devices, and other emerging therapies in men with different causes of ED. CONCLUSION: Available economic evaluations of ED therapies are dated, do not reflect present-day physician, pharmaceutical, and device costs, fail to account for patient comorbidities, and may not be generalizable to today's ED patients. Substantial research is needed to evaluate the cost-effectiveness of ED treatments across different patient populations, countries, and reimbursement systems. Rezaee ME, Ward CE, Brandes ER, et al. A Review of Economic Evaluations of Erectile Dysfunction Therapies. Sex Med Rev 2019;8:497-503.

Economic evaluation of sildenafil for the treatment of pulmonary arterial hypertension in Indonesia.

BACKGROUND: This study aims to assess the cost-effectiveness and budget impact of adopting sildenafil to the benefits package for the indication of pulmonary arterial hypertension (PAH), compared to beraprost. METHODS: Based on a societal perspective, a model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). RESULTS: The economic model calculated the incremental cost-effectiveness ratio (ICER) per QALY gained for using sildenafil as first-line therapy compared to beraprost for the patient in functional class (FC) II and III, i.e. USD 3098 and USD 2827, respectively. The results indicated that in spite of sildenafil being more expensive than beraprost, generic sildenafil could potentially be a good value for money since ICER per QALY is below one times gross domestic product (GDP) per capita in Indonesia. Furthermore, budget impact analysis estimated that the incremental budget needed within 5 years for including sildenafil compared to beraprost for PAH patients starting in FC II and FC III was USD 436,775 and USD 3.6 million, respectively. CONCLUSIONS: Compared to beraprost, sildenafil would be preferable for the treatment of PAH patients in FC II and FC III in Indonesia. The additional budget for adopting sildenafil compared to beraprost as the treatment of PAH in the benefits package was estimated at around USD 4.0 million.

Eficacia y seguridad de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional II / Efficacy and safety of inhaled iloprost plus oral sildenafil compared with oral sildenafil in pregnant patients with functional class II pulmonary arterial hypertension

 INTRODUCCIÓN: La hipertensión pulmonar abarca un grupo de enfermedades de rara presentación que se caracterizan por una elevación crónica de la resistencia vascular pulmonar. La prevalencia estimada de la hipertensión pulmonar es de alrededor de cinco casos por millón de habitantes, por lo cual, es considerada una enfermedad rara. Se recomienda de manera general que las mujeres con hipertensión pulmonar eviten quedar embarazadas ante el riesgo de complicaciones materno-fetales y alta mortalidad que presenta la enfermedad. En el Petitorio Farmacológico de EsSalud se dispone de sildenafilo para el tratamiento de pacientes con hipertensión pulmonar. No obstante, en pacientes gestantes con hipertensión pulmonar y con deterioro de la clase funcional III luego de recibir un tratamiento adecuado con sildenafilo; podrían requerir la combinación de este último con otros fármacos. Iloprost pertenece al grupo farmacológico de los análogos de la prostaciclina. Se administra por vía inhalatoria y actúa mediante la vasodilatación del lecho arterial pulmonar. OBJETIVO: Evaluar la eficacia y seguridad del uso de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional III. Tecnología Sanitaria de Interés: Iloprost: Los aspectos generales de iloprost (Nombre comercial: Ventavis®, Bayer) se describen a profundidad en el Dictamen Preliminar de Evaluación de Tecnología Sanitaria N.° 001-SDEPFyOTS-DETS-IETSI-2015. A continuación de describirán las características más relevantes de la tecnología sanitaria de interés. Iloprost es un medicamento perteneciente al grupo farmacológico de los análogos de la prostaciclina que se administra por vía inhalatoria. Tras la inhalación se produce una vasodilatación del lecho arterial pulmonar con una mejoría de la presión arterial pulmonar, de la resistencia vascular pulmonar, del gasto cardiaco y de la saturación de la mezcla venosa de oxígeno. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva y jerárquica de la literatura biomédica para evaluar la eficacia y seguridad de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional III. Además, para complementar la evidencia y describir la tecnología sanitaria de interés, se revisó en primer lugar la información de etiqueta disponible por entes reguladores y normativos de autorización comercial como la FDA en Estados Unidos, EMA en Europa, y DIGEMID en Perú. RESULTADOS: De acuerdo con la pregunta PICO de interés, se llevó a cabo una búsqueda de evidencia científica, sin restricción temporal ni de idioma, relacionada al uso de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional III. En la presente sinopsis se reporta la evidencia disponible según el tipo de publicación priorizada en los criterios de inclusión; no obstante, a la fecha no se ha publicado un ECA o RS acerca de la tecnología evaluada que incluya a la población de interés. Por lo tanto, se reportan las publicaciones obtenidas de una búsqueda complementaria de estudios observacionales acerca del uso de iloprost en pacientes gestantes. CONCLUSIONES: En el presente documento se evaluó la evidencia científica publicada hasta la actualidad en relación al uso de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional III. Luego de una búsqueda bibliográfica exhaustiva, no se identificó evidencia que evalúe la eficacia y seguridad de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional III. En tal sentido, se adicionó una búsqueda específica de estudios observacionales que incluyan gestantes con hipertensión pulmonar. Se identificaron dos GPC que solo recomiendan a las mujeres con HAP eviten el embarazo. No se incluyen recomendaciones terapéuticas para la población de la pregunta PICO del presente dictamen. Sin embargo, en pacientes que continúan sintomáticos con dosis apropiadas y continuas de un inhibidor de la 5-fosfodiesterasa (ej. sildenafilo) o antagonistas de receptores de endotelina (contraindicado en el embarazo) se recomienda por consenso de expertos el uso combinado con iloprost inhalado para mejorar la clase funcional y retrasar el deterioro clínico. Las series de casos encontradas son poco precisas para proveer información sobre cada uno de los tratamientos recibidos (monoterapia vs. terapia combinada) al indicar en algunos casos solo el grupo farmacológico. En cuando a la tecnología evaluada en el presente dictamen, se observa que los análogos de la prostaciclina son empleados y representan una alternativa en el manejo de pacientes gestantes con HAP. De este modo, a pesar de la ausencia de evidencia que respalde el beneficio terapéutico de iloprost inhalado más sildenafilo oral comparado con sildenafilo oral en pacientes gestantes con hipertensión arterial pulmonar de clase funcional III, el uso de iloprost puede ser considerado una alternativa terapéutica para tratamientos combinados con sildenafilo, estando este último disponible en EsSalud. Además, se debe considerar que, de acuerdo a las opiniones de los especialistas de la institución, la evolución de la enfermedad y la falta de alternativas dentro del Petitorio de EsSalud nos encontraríamos ante un vacío terapéutico frente a una paciente gestante con deterioro de la hipertensión arterial pulmonar de clase funcional III a pesar de recibir un tratamiento adecuado con sildenafilo. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI aprueba el uso fuera del petitorio de iloprost en combinación con sildenafilo pacientes gestantes con hipertensión arterial pulmonar de clase funcional III. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review.

Objectives: Although many studies have reported on the cost-effectiveness of bosentan for treating pulmonary arterial hypertension (PAH), a systematic review of economic evaluations of bosentan is currently lacking. Objective evaluation of current pharmacoeconomic evidence can assist decision makers in determining the appropriate place in therapy of a new medication. Methods: Systematic literature searches were conducted in English-language databases (MEDLINE, EMBASE, EconLit databases, and the Cochrane Library) and Chinese-language databases (China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP) to identify studies assessing the cost-effectiveness of bosentan for PAH treatments. Results: A total of 8 published studies were selected for inclusion. Among them were two studies comparing bosentan with epoprostenol and treprostinil. Both results indicated that bosentan was more cost-effective than epoprostenol, while the results of bosentan and treprostinil were not consistent. Four studies compared bosentan with other endothelin receptor antagonists, which indicated ambrisentan might be the drug of choice for its economic advantages and improved safety profile. Only two economic evaluations provided data to compare bosentan versus sildenafil, and the results favored the use of sildenafil in PAH patients. Four studies compared bosentan with conventional, supportive, or palliative therapy, and whether bosentan was cost-effective was uncertain. Conclusions: Bosentan may represent a more cost-effective option compared with epoprostenol and conventional or palliative therapy. There was unanimous agreement that bosentan was not a cost-effective front-line therapy compared with sildenafil and other endothelin receptor antagonists. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.

Análisis de impacto presupuestal de ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, sildenafil y treprostinil para el tratamiento de pacientes con Hipertensión Arterial Pulmonar Grupo 1 en Colombia / Budget impact analysis of ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, sildenafil and treprostinil for the treatment of patients with hypertension Pulmonary Artery Group 1 in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) de ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, sildenafil y treprostinil para el tratamiento de pacientes con Hipertensión Arterial Pulmonar Grupo 1 en Colombia, se desarrolló en el marco del mecanismo técnico-científico para la ampliación progresiva del Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Regulación de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. La hipertensión arterial pulmonar grupo 1 (HAPG1) es una enfermedad progresiva causada por el estrechamiento o constricción de las arterias pulmonares que conectan el lado derecho del corazón con los pulmones. La HAPG1 se caracteriza por un aumento en la presión arterial pulmonar media (PAP) ≥25 mmHg en reposo y una presión capilar primaria media ≤15 mmHg (1). A medida que se desarrolla la HAPG1, el flujo de sangre a través de las arterias pulmonar