Naftidrofuryl 100mg/5ml oral solution

BACKGROUND: Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. OBJECTIVE: To assess the effectiveness and cost-effectiveness of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. DATA SOURCE: Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS: Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. RESULTS: Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100-500 per year for the other drugs). CONCLUSIONS: Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.

Abstract licence: CC BY

OBJECTIVE: To assess the efficacy of naftidrofuryl compared with placebo in treating the symptoms of intermittent claudication. DESIGN: Meta-analysis based on individual patient data. DATA SOURCES: Medline, International Pharmaceutical Abstracts, Embase, Science Citation Index, and the Cochrane trial registers. Reference lists of retrieved articles were checked. Authors and companies were approached for additional information and individual patient data. INCLUSION CRITERIA: Double blind, randomised controlled trials in patients with intermittent claudication receiving oral naftidrofuryl or placebo and with pain-free walking distance as primary outcome. DATA COLLECTION: Individual patient data were collected from electronic data or from case report forms and checked for integrity. ANALYSIS: All randomised patients were analysed following the intention to treat principle. Efficacy was assessed by the ratio of geometric mean of the relative improvement in pain-free walking distance after use of naftidrofuryl compared with placebo. In the analysis of responders, therapeutic success was defined as an improvement of walking distance at baseline by at least 50%. RESULTS: In total, 1266 patients were randomised (1083 in the main analysis). The ratio of relative improvement in pain-free walking distance after use of naftidrofuryl compared with placebo was 1.37 (95% confidence interval 1.27 to 1.49). The difference in response rate was 22.3% (95% confidence interval 17.1% to 27.6%) and the number needed to treat for relief of symptoms during six months of treatment was 4.48 (95% confidence interval 3.62 to 5.85). CONCLUSION: This meta-analysis of individual patient data provides evidence that naftidrofuryl has a clinically meaningful effect compared with placebo in improving walking distance in patients with intermittent claudication.

Abstract licence: CC BY-NC

BACKGROUND: Age-related hearing loss (ARHL) is a common sensory disorder with significant public health implications. However, few effective treatment options are available. Mendelian randomization (MR) has been used to repurpose existing drugs and identify new therapeutic targets. Therefore, we performed a systematic genome-wide MR of drug-eligible individuals to explore potential therapeutic targets for ARHL. METHODS: We obtained data on the expression quantitative trait locis (eQTLs) of druggable genes, which were then subjected to two-sample MR analyses and co-localisation analyses with data from the ARHL genome-wide association study to identify genes highly associated with ARHL. Additionally, we conducted phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking to help develop more effective and targeted therapeutic treatments. RESULTS: Overall, the MR analysis of eQTL data showed that 14 drug targets were significantly associated with ARHL. GO analysis of 14 potential targets revealed their primary involvement in biological processes such as the endoplasmic reticulum unfolded protein response, ER-nucleus signaling pathway, and fibroblast apoptotic process. Additionally, important cellular components include the Bcl-2 family of proteins and the endoplasmic reticulum lumen. After filtering using methods such as phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking, six potentially druggable genes (BAK1, AMFR, LAMP3, STK17B, ACP5, and CD9) and six drugs (beclomethasone, propyl pyrazole triol, momelotinib, monoisoamyl-2,3-dimercaptosuccinate, pterostilbene, and naftidrofuryl) that may affect ARHL outcomes were finally identified. CONCLUSIONS: Our findings identified 14 potential drug targets for ARHL. These findings offer promising leads for more effective treatments for ARHL and help determine the priority of drug development, potentially reducing costs.

Abstract licence: CC BY-NC-ND