Alice K. Jacobs, MD, FACC, FAHA, Chair 

Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect 

Nancy Albert, PhD, CCNS, CCRN, FAHA

Mark A. Creager, MD, FACC, FAHA

Steven M. Ettinger, MD, FACC

Robert A. Guyton, MD, FACC

Jonathan L. Halperin, MD, FACC, FAHA

Judith S. Hochman, MD, FACC, FAHA

2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)61069-2.pdf

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

http://www.botonimarco.it/files/linee_guida_2011_accf_aha_scai_percutaneus_coronar.pdf

2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]

Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]

Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]

Nancy M

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).

Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD.

Conclusion Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

/pdf/familial-hypercholesterolaemia-is-underdiagnosed-and-f73455ifi9.pdf

Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society

The statistic of interest in the economic evaluation of health care interventions is the incremental cost effectiveness ratio (ICER), which is defined as the difference in cost between two treatment interventions over the difference in their effect. Where patient-specific data on costs and health outcomes are available, it is natural to attempt to quantify uncertainty in the estimated ICER using confidence intervals. Recent articles have focused on parametric methods for constructing confidence intervals. In this paper, we describe the construction of non-parametric bootstrap confidence intervals. The advantage of such intervals is that they do not depend on parametric assumptions of the sampling distribution of the ICER. We present a detailed description of the non-parametric bootstrap applied to data from a clinical trial, in order to demonstrate the strengths and weaknesses of the approach. By examining the bootstrap confidence limits successively as the number of bootstrap replications increases, we conclude that percentile bootstrap confidence interval methods provide a promising approach to estimating the uncertainty of ICER point estimates. However, successive bootstrap estimates of bias and standard error suggests that these may be unstable; accordingly, we strongly recommend a cautious interpretation of such estimates.

Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation.

Objectives: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity Data sources: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). Review methods: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios ( OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi- squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. Results: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs ( doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was pound250 and pound1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. Conclusions: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

/pdf/a-systematic-review-of-the-role-of-bisphosphonates-in-o1merva1fv.pdf

A systematic review of the role of bisphosphonates in metastatic disease.

Objectives: To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. Design: Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. Participants: Simulated population aged 16-54 years in England and Wales. Interventions: Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. Main outcome measure: Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. Results: Tracing of family members was the most cost effective strategy (£3097 (€5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of £133 per case detected. If the genetic mutation was known within the family then the cost per life year gained (£4914) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (£13 029 per life year gained) as 1365 individuals need to be screened at a cost of £9754 per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (£2777 with a clinical confirmation). Conclusions: Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population.

https://www.bmj.com/content/bmj/324/7349/1303.full.pdf

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

Objective To evaluate the cost effectiveness of acupuncture in the management of chronic headache.

Design Cost effectiveness analysis of a randomised controlled trial.

Setting General practices in England and Wales.

Participants 401 patients with chronic headache, predominantly migraine.

Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists, or to usual care alone.

Main outcome measure Incremental cost per quality adjusted life year (QALY) gained.

Results Total costs during the one year period of the study were on average higher for the acupuncture group (£403; $768; €598) than for controls (£217) because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years (QALYs), leading to a base case estimate of £9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial.

Conclusions Acupuncture for chronic headache improves health related quality of life at a small additional cost; it is relatively cost effective compared with a number of other interventions provided by the NHS.

https://www.bmj.com/content/bmj/328/7442/747.full.pdf

Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care.

BACKGROUND: In the majority of people with familial hypercholesterolaemia (FH) the disorder is caused by a mutation of the low-density lipoprotein receptor gene that impairs its proper function, resulting in very high levels of plasma cholesterol. Such levels result in early and severe atherosclerosis, and hence substantial excess mortality from coronary heart disease. Most people with FH are undiagnosed or only diagnosed after their first coronary event, but early detection and treatment with hydroxymethylglutaryl-coenzyme (HMG CoA) reductase inhibitors (statins) can reduce morbidity and mortality. The prevalence of FH in the UK population is estimated to be 1 in 500, which means that approximately 110,000 people are affected. OBJECTIVES: To evaluate whether screening for FH is appropriate. To determine which system of screening is most acceptable and cost-effective. To assess the deleterious psychosocial effects of genetic and clinical screening for an asymptomatic treatable inherited condition. To assess whether the risks of screening outweigh potential benefits. METHODS: DATA SOURCES: Relevant papers were identified through a search of the electronic databases. Additional papers referenced in the search material were identified and collected. Known researchers in the field were contacted and asked to supply information on unpublished or ongoing studies. INCLUSION/EXCLUSION CRITERIA: SCREENING AND TREATMENT: The review included studies of the mortality and morbidity associated with FH, the effectiveness and cost of treatment (ignoring pre-statin therapies in adults), and of the effectiveness or cost of possible screening strategies for FH. PSYCHOSOCIAL EFFECTS OF SCREENING: The search for papers on the psychological and social effects of screening for a treatable inherited condition was limited to the last 5 years because recent developments in genetic testing have changed the nature and implications of such screening tests. Papers focusing on genetic testing for FH and breast cancer were included. Papers relating to the risk of coronary heart disease with similarly modifiable outcome (non- FH) were also included. DATA EXTRACTION AND ASSESSMENT OF VALIDITY: A data assessment tool was designed to assess the quality and validity of the papers which reported primary data for the social and psychological effects of screening. Available guidelines for systematically reviewing papers concentrated on quantitative methods, and were of limited relevance. An algorithm was developed which could be used for both the qualitative and quantitative literature. MODELLING METHODS: A model was constructed to investigate the relative cost and effectiveness of various forms of population screening (universal or opportunistic) and case-finding screening (screening relatives of known FH cases). All strategies involved a two-stage process: first, identifying those people with cholesterol levels sufficiently elevated to be compatible with a diagnosis of FH, and then either making the diagnosis based on clinical signs and a family history of coronary disease or carrying out genetic tests. Cost-effectiveness has been measured in terms of incremental cost per year of life gained. RESULTS: MODELLING COST- EFFECTIVENESS: FH is a life-threatening condition with a long presymptomatic state. Diagnostic tests are reasonably reliable and acceptable, and treatment with statins substantially improves prognosis. Therefore, it is appropriate to consider systematic screening for this condition. Case finding amongst relatives of FH cases was the most cost-effective strategy, and universal systematic screening the least cost-effective. However, when targeted at young people (16 year olds) universal screening was also cost-effective. Screening patients admitted to hospital with premature myocardial infarction was also relatively cost-effective. Screening is least cost- effective in men aged over 35 years, because the gains in life expectancy are small. (ABSTRACT TRUNCA

/pdf/screening-for-hypercholesterolaemia-versus-case-finding-for-3lmdw09enc.pdf

David Wonderling

Papers

Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation.

A systematic review of the role of bisphosphonates in metastatic disease.

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care.

Screening for hypercholesterolaemia versus case finding for familial hypercholesterolaemia: a systematic review and cost-effectiveness analysis.