Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction : systematic review and economic evaluation

Background The blockage of a coronary artery (coronary thrombosis) can lead to a heart attack (acute myocardial infarction). There are several ways of trying to overcome this blockage. The methods include drug treatment to dissolve the clot (thrombolysis) and physical intervention, either by passing a catheter into the affected artery [angioplasty or percutaneous coronary intervention (PCI)], or bypassing the blocked section by cardiac surgery [coronary artery bypass grafting (CABG)]. Thrombolysis can be given in the community before the patient is sent to hospital, or delayed until after admission. Prehospital thrombolysis is not common in the UK. Immediate angioplasty is not routinely available in the UK at present; it is much more common in the USA. Objectives To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. Methods This report was based on a systematic review of the evidence of clinical effectiveness and an economic analysis of cost-effectiveness based on the clinical review and on cost data from published sources and de novo data collection. Data sources The search strategy searched six electronic databases (including Medline, Cochrane Library and EMBASE), with English-language limits, for the periods up to December 2002. Bibliographies of related papers were assessed for relevant studies and experts contacted for advice and peer review, and to identify additional published and unpublished references. Study selection For clinical effectiveness, a comprehensive review of randomised controlled trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data for effectiveness safety in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. They were used to assess the implications of wider diffusion of the technology away from major centres. Data extraction Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of systematic reviews, RCTs, controlled clinical trials and economic studies was assessed using criteria recommended by the NHS Centre for Reviews and Dissemination (University of York). Study synthesis Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). Results and conclusion Number and quality of studies, and summary of benefits There were several good-quality systematic reviews, including a Cochrane review, as well as an individual patient meta-analysis and a number of recent trials not included in the reviews. The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with PCI, with the difference being due to haemorrhagic stroke. The need for CABG is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. One good quality study from France showed that prehospital thrombolysis with PCI in those in whom thrombolysis failed was as good as universal PCI. Research on thrombolysis followed by PCI, known as facilitated PCI, is underway, but results are not yet available. Further caveats are needed. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than 1 hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Cost-effectiveness If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost and an incremental cost per unit change in health status under the £30,000 threshold in most instances. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. The model is not particularly sensitive to variations in probabilities from the clinical effectiveness analysis. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, could be used. In rural areas, one option could be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. Need for further research There is a need for economic data on the long-term consequences of the treatment, the quality of life of patients after treatment and the effects of PCI following thrombolysis failure

The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

Background: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF. Methods: Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken. Results: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective. Conclusions: Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered

The cost-effectiveness of left ventricular assist devices in end stage heart failure

With a limited supply of donor hearts, individuals with end-stage heart failure have been offered hope through the use of mechanical devices. Left ventricular-assist devices (LVADs) are a technology designed to work in parallel with the heart but have yet to see widespread use since uncertainty remains as to the cost–effectiveness of this evolving new technology. We have systematically reviewed evidence of cost–effectiveness for LVADs in the bridge-to-transplant and long-term chronic support indications. A total of 18 studies reporting costs were identified. Of these, only four studies reported results in cost–effectiveness terms; two in cost per life-year saved and two in cost per quality-adjusted life-year (QALY). The majority of the other studies were simple cost summations (cost per day or incremental cost) without consideration of efficacy. In the bridge-to-transplant indication, a Danish abstract reported a cost per life-year saved of DKK270k (US$48,000), a UK study reported a cost per QALY of GB£39,787 (US$78,000) and a Canadian study reported a cost per life-year saved of Can$91,332 (US$86,000). Regarding the long-term chronic support indication, the same Canadian study reported a cost per life-year saved of Can$59,842 (US$56,000), whereas a US study reported a cost per QALY of $36,255–60,057. Assuming a willingness to pay the threshold of GB£30,000 (US$59,000) per QALY, there is arguably stronger evidence to support the cost–effectiveness of LVAD technology for the long-term chronic support indication. However, the methodological quality of the majority of studies was poor, as was their generalizability, raising concerns over the reliability of these figures. With the limited and declining availability of donor hearts for transplantation, it appears that the future of this technology is in its use as long-term chronic support. Further analyses should be undertaken, particularly alongside randomized, controlled trials and utilizing second- and third-generation devices<br/

Cirugía Para La Obesidad

Antecedentes: Se considera la cirugía bariátrica (para la disminución del peso) como un tratamiento de la obesidad cuando han fracasado otros tratamientos. Los efectos de los procedimientos bariátricos disponibles son inciertos comparados con el tratamiento médico y entre ellos. Ésta es una actualización de la revisión sistemática Cochrane publicada por primera vez en 2003 y actualizada en 2005. Objetivo: Evaluar los efectos de la cirugía bariátrica para la obesidad. Estratégia de búsqueda: Los estudios se identificaron en búsquedas electrónicas en múltiples bases de datos bibliográficas, complementadas con búsquedas en listas de referencias y con la consulta con expertos en la investigación sobre la obesidad. Criterios de selección: Ensayos controlados aleatorios (ECA) que compararon diferentes procedimientos quirúrgicos, y ensayos controlados aleatorios (ECA), ensayos clínicos controlados y estudios de cohortes prospectivos que compararon la cirugía con el tratamiento no quirúrgico de la obesidad. Obtención y análisis de datos: Los datos fueron extraídos por un revisor y verificados independientemente por dos revisores. Dos revisores de forma independiente evaluaron la calidad de los ensayos. Resultados principales: Se incluyeron 26 estudios. Tres ensayos controlados aleatorios y tres estudios de cohortes prospectivos compararon la cirugía con el tratamiento no quirúrgico, y 20 ensayos controlados aleatorios compararon diferentes procedimientos bariátricos. El riesgo de sesgo de muchos ensayos fue incierto; y sólo cinco tuvieron una adecuada ocultación de la asignación. No era apropiado un metanálisis. El tratamiento quirúrgico dio como resultado una mayor pérdida de peso que el tratamiento convencional en la obesidad moderada (índice de masa corporal mayor de 30), así como en la grave. Hubo también disminución de las comorbilidades, como la diabetes y la hipertensión. Después de dos años mejoró la calidad de vida relacionada con la salud, pero los efectos a los diez años están menos claros. El tratamiento quirúrgico se asocia con complicaciones, como la embolia pulmonar, y ocurrieron algunas muertes posoperatorias. Se evaluaron cinco procedimientos bariátricos diferentes, pero algunas comparaciones fueron evaluadas sólo en un ensayo. Las limitadas pruebas indican que la pérdida de peso después de la derivación gástrica es mayor que con la gastroplastia en banda vertical o con la banda gástrica regulable, pero similar a la gastrectomía en manga aislada y a la derivación gástrica en banda. La gastrectomía en manga aislada parece que produce mayor pérdida de peso que la banda gástrica regulable. Las pruebas que comparan la gastroplastia en banda vertical con la banda gástrica regulable no son concluyentes. Los datos sobre la seguridad comparativa de los procedimientos bariátricos fueron limitados. La pérdida de peso y la calidad de vida fueron similares entre la cirugía abierta y los procedimientos laparoscópicos. Puede ocurrir que la cirugía laparoscópica termine como una intervención quirúrgica abierta. Conclusiones de los autores: El tratamiento quirúrgico es más efectivo que el tratamiento convencional. Ciertos procedimientos producen mayor pérdida de peso, pero los datos son limitados. Las pruebas sobre la seguridad son aún menos claras. Deben ser interpretados con cuidado la seguridad y la efectividad comparativas, debido a las limitaciones de las pruebas y a la deficiente calidad de los ensayos

Dietary fibre for the primary prevention of cardiovascular disease (protocol)

Background The prevention of cardiovascular disease (CVD) is a key public health priority. A number of dietary factors have been associated with modifying CVD risk factors. One such factor is dietary fibre which may have a beneficial association with CVD risk factors. There is a need to review the current evidence from randomised controlled trials (RCTs) in this area. Objectives The primary objective of this systematic review was to determine the effectiveness of dietary fibre for the primary prevention of CVD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Ovid MEDLINE (1946 to January 2015), Ovid EMBASE (1947 to January 2015) and Science Citation Index Expanded (1970 to January 2015) as well as two clinical trial registers in January 2015. We also checked reference lists of relevant articles. No language restrictions were applied. Selection criteria We selected RCTs that assessed the effects of dietary fibre compared with no intervention or a minimal intervention on CVD and related risk factors. Participants included adults who are at risk of CVD or those from the general population. Data collection and analysis Two authors independently selected studies, extracted data and assessed risk of bias; a third author checked any differences. A different author checked analyses. Main results We included 23 RCTs (1513 participants randomised) examining the effect of dietary fibre. The risk of bias was unclear for most studies and studies had small sample sizes. Few studies had an intervention duration of longer than 12 weeks. There was a wide variety of fibre sources used, with little similarity between groups in the choice of intervention. None of the studies reported on mortality (total or cardiovascular) or cardiovascular events. Results on lipids suggest there is a significant beneficial effect of increased fibre on total cholesterol levels (17 trials (20 comparisons), 1067 participants randomised, mean difference -0.20 mmol/L, 95% CI -0.34 to -0.06), and LDL cholesterol levels (mean difference -0.14 mmol/L, 95% CI -0.22 to -0.06) but not on triglyceride levels (mean difference 0.00 mmol/L, 95% CI -0.04 to 0.05), and there was a very small but statistically significant decrease rather than increase in HDL levels with increased fibre intake (mean difference -0.03 mmol/L, 95% CI -0.06 to -0.01). Fewer studies (10 trials, 661 participants randomised) reported blood pressure outcomes where there is a significant effect of increased fibre consumption on diastolic blood pressure (mean difference -1.77 mmHg, 95% CI -2.61 to -0.92) whilst there is a reduction in systolic blood pressure with fibre but this does not reach statistical significance (mean difference -1.92 mmHg, 95% CI -4.02 to 0.19). There did not appear to be any subgroup effects by the nature of the type of intervention (fibre supplements or provision of foods/advice to increase fibre consumption) or the type of fibre (soluble/insoluble) although the number of studies contributing to each subgroup were small. All analyses need to be viewed with caution given the risks of bias observed for total cholesterol and the statistical heterogeneity observed for systolic blood pressure. Adverse events, where reported, appeared to mostly reflect mild to moderate gastrointestinal side-effects and these were generally reported more in the fibre intervention groups than the control groups. Authors' conclusions Studies were short term and therefore did not report on our primary outcomes, CVD clinical events. The pooled analyses for CVD risk factors suggest reductions in total cholesterol and LDL cholesterol with increased fibre intake, and reductions in diastolic blood pressure. There were no obvious effects of subgroup analyses by type of intervention or fibre type but the number of studies included in each of these analyses were small. Risk of bias was unclear in the majority of studies and high for some quality domains so results need to be interpreted cautiously. There is a need for longer term, well-conducted RCTs to determine the effects of fibre type (soluble versus insoluble) and administration (supplements versus foods) on CVD events and risk factors for the primary prevention of CVD

Weight loss surgery for mild to moderate obesity: a systematic review and economic evaluation.

Bariatric surgery appears to be a clinically effective and cost-effective intervention for people with class I or II obesity who also have T2D but is less likely to be cost-effective for people with class I obesit

Dasatinib, high dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation

Treatments for patients with CML have included hydroxycarbamide, interferon alfa, stem cell transplantation and acute leukaemia-style chemotherapy. More recently, tyrosine-kinase inhibitor drugs have been developed. Imatinib was the first tyrosine-kinase inhibitor to be used for treating CML. It is considered to be effective and is recommended by NICE for the treatment of CML in the first line.1 Subsequently, dasatinib and nilotinib, also tyrosine-kinase inhibitors, have been developed and are being used for the treatment of CML.Guidance on second-line treatment for those patients developing resistance to imatinib is less clear. In clinical practice, imatinib at high doses is frequently used. Dasatinib and nilotinib may also be treatment options. However, there have been no evaluations of the clinical and cost effectiveness of these treatments compared to each other or to most of the older treatment options for patients with imatinib-resistant CML. Economic evaluations of dasatinib and nilotinib compared to interferon alfa with cytarabine have been conducted (appendix 8 of CML assessment report2).The function of this review is therefore to assess the clinical and cost effectiveness of high dose imatinib, dasatinib and nilotinib compared to each other or traditional technologies such as hydroxycarbamide, interferon alfa, stem cell transplantation and acute chemotherapy for the treatment of patients with imatinib-resistant CML. This report is a part update of a previous report undertaken to inform the NICE MTA of dasatinib and nilotinib for people with imatinib resistant and imatinib intolerant CML,2 where the current report focuses on those with imatinib resistant disease only.The HTA Programme commisioned this technology assessment report on behalf of the National Institute for Health and Clinical Excellence

Comparing new treatments for idiopathic pulmonary fibrosis - a network meta-analysis

BACKGROUND: The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison.METHODS: We searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation.RESULTS: Of 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone.CONCLUSIONS: Two treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.</p

The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF.METHODS: Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken.RESULTS: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective.CONCLUSIONS: Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered.</p