WITHDRAWN: Celecoxib for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence. SEARCH METHODS: We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data. MAIN RESULTS: Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin. AUTHORS' CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.

Determining the in-hospital cost of bleeding in patients undergoing percutaneous coronary intervention.

BACKGROUND: The economic impact of bleeding in the setting of nonemergent percutaneous coronary intervention (PCI) is poorly understood and complicated by the variety of bleeding definitions currently employed. This retrospective analysis examines and contrasts the in-hospital cost of bleeding associated with this procedure using six bleeding definitions employed in recent clinical trials. METHODS: All nonemergent PCI cases at Christiana Care Health System not requiring a subsequent coronary artery bypass were identified between January 2003 and March 2006. Bleeding events were identified by chart review, registry, laboratory, and administrative data. A microcosting strategy was applied utilizing hospital charges converted to costs using departmental level direct cost-to-charge ratios. The independent contributions of bleeding, both major and minor, to cost were determined by multiple regression. Bootstrap methods were employed to obtain estimates of regression parameters and their standard errors. RESULTS: A total of 6,008 cases were evaluated. By GUSTO definitions there were 65 (1.1%) severe, 52 (0.9%) moderate, and 321 (5.3%) mild bleeding episodes with estimated bleeding costs of $14,006; $6,980; and $4,037, respectively. When applying TIMI definitions there were 91 (1.5%) major and 178 (3.0%) minor bleeding episodes with estimated costs of $8,794 and $4,310, respectively. In general, the four additional trial-specific definitions identified more bleeding events, provided lower estimates of major bleeding cost, and similar estimates of minor bleeding costs. CONCLUSIONS: Bleeding is associated with considerable cost over and above interventional procedures; however, the choice of bleeding definition impacts significantly on both the incidence and economic consequences of these events.

Cost-effectiveness of treatments reducing coronary heart disease mortality in Ireland, 2000 to 2010.

OBJECTIVE: Coronary heart disease (CHD) is associated with a large burden of disease in Ireland and is responsible for more than 6000 deaths annually. This study examined the cost-effectiveness of specific CHD treatments in Ireland. METHODS: Irish epidemiological data on patient numbers and median survival in specific groups, plus the uptake, effectiveness, and costs of specific interventions, all stratified by age and sex, were incorporated into a previously validated CHD mortality model, the IMPACT model. This model calculates the number of life-years gained (LYGs) by specific cardiology interventions to generate incremental cost-effectiveness ratios (ICERs) per LYG for each intervention. RESULTS: In 2000, medical and surgical treatments together prevented or postponed approximately 1885 CHD deaths in patients aged 25 to 84 years, and thus generated approximately 14,505 extra life-years (minimum 7270, maximum 22,475). In general, all the cardiac interventions investigated were highly cost-effective in the Irish setting. Aspirin, beta-blockers, ACE inhibitors, spironolactone, and warfarin for specific conditions were the most cost-effective interventions (< euro 3000/LYG), followed by the statins for secondary prevention (< euro 6500/LYG). Revascularization for chronic angina and primary angioplasty for myocardial infarction, although still cost-effective, had the highest ICER (between euro 12,000 and euro 20,000/LYG). CONCLUSIONS: Using a comprehensive standardized methodology, cost-effectiveness ratios in this study clearly favored simple medical treatments for myocardial infarction, secondary prevention, angina, and heart failure.

Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation.

AIMS: To estimate costs of admission and costs incurred on an annual basis by patients with atrial fibrillation (AF) in Greece, Italy, Poland, Spain, and the Netherlands. METHODS AND RESULTS: The Euro Heart Survey on AF enrolled 5333 patients with AF in 35 European countries in 2003 and 2004. This was a bottom-up cost study conducted for the five largest contributors in terms of patients enrolled. Quantities of resource use during the enrolment admission and during 1-year follow-up were inferred from survey data and multiplied by national unit costs in order to estimate per patient costs associated with AF for each country. Mean costs of inpatient admission of an AF patient were estimated at euro1363, euro5252, euro2322, euro6360, and euro6445 and mean costs incurred on an annual basis at euro1507, euro3225, euro1010, euro2315, and euro2328 in Greece, Italy, Poland, Spain, and the Netherlands, respectively. Inpatient care and interventional procedures were identified as the main drivers of costs, accounting for more than 70% of total annual costs in all five countries. CONCLUSION: Estimates of the economic burden posed by AF are critical in light of the increasing importance of AF as a public health problem.

The risk of cardiovascular events in primary care patients following an episode of severe hypertension.

This retrospective study of office and hospital electronic medical records from June 1991 to June 2007 examines the occurrence of severe blood pressure (BP) elevation (>180/110 mm Hg) and the subsequent risk of cardiovascular events in a diverse set of primary care practices. A total of 18,747 patients were categorized according to BP using 3 methodologies based on the highest historical value, the first recorded value, and time-averaged antecedent values. During the follow-up period (median 3.8 years) there were 949 cardiovascular events and 80 cardiovascular-related deaths. Severe BP elevation occurred in 1566 (8.4%) patients. The age-adjusted incidence of cardiovascular events per 1000 patient-years was 5.9 in the normal BP group, 10.1 in the mild group, 15.1 in the moderate group, and 25.0 in the severe group. An episode of severe BP elevation is common in primary care practice and is associated with substantial excess cardiovascular morbidity.

Cost-effectiveness of clopidogrel treatment in percutaneous coronary intervention: a European model based on a meta-analysis of the PCI-CURE, CREDO and PCI-CLARITY trials.

OBJECTIVE: Our objective was to conduct a comprehensive cost-effectiveness analysis of pre-treatment and long-term treatment with clopidogrel in percutaneous coronary intervention (PCI) in three European countries based on a meta-analysis of the PCI-Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel for the Reduction of Events During Observation (CREDO) and PCI-Clopidogrel as Adjunctive Therapy (CLARITY) trials. This analysis adds to existing knowledge by providing further data on the cost-effectiveness of clopidogrel in PCI across a wide spectrum of patients. METHODS: A combined decision tree and Markov model was created. The relative risks of myocardial infarction, cardiovascular death and of major bleedings with clopidogrel were based on a fixed-effects meta-analysis. The risk of ischaemic events in untreated patients and long-term survival were taken from the Swedish hospital and death registers. A societal perspective was used in Sweden and a payer perspective in Germany and France. Costs are stated in euro2006 and effectiveness measured in quality-adjusted life-years (QALYs). RESULTS: The pooled effects of clopidogrel on the combined endpoint showed a relative risk of 0.711 (p=0.003) at 30 days and 0.745 (p=0.002) at end of follow-up (up to 1 year). Pre-treatment with clopidogrel compared with aspirin alone is a dominant strategy. Long-term treatment with clopidogrel compared with 1-month treatment leads to approximately 0.09 QALYs at an incremental cost of euro393 in Sweden, euro709 in Germany and euro494 in France. The corresponding incremental cost-effectiveness ratios range from euro4225/QALY to euro7871/QALY. CONCLUSION: The results of this modelling analysis suggest that pre-treatment and long-term treatment in PCI with clopidogrel for up to 1 year are cost-effective in a range of patient groups and settings given commonly accepted thresholds.

Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism.

Venous thromboembolism (VTE) is a major US health problem. However, the total number of US inpatients who are at risk for VTE is unknown. Our objective was to estimate the number of US acute-care hospital inpatients who were at risk for VTE according to criteria established by the Seventh American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic and Thrombolytic Therapy guidelines for VTE prevention. Using the 2003 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP), patient diagnoses and procedures were examined to identify major surgery patients (age > or = 18 years, length of hospital stay > or = 2 days) and medical patients (age > or = 40 years, length of hospital stay > or = 2 days). ACCP guidelines were used to estimate the number of surgical and medical patients at risk of developing VTE. Of an estimated 38,220,659 discharges in 2003, 7,786,390 (20%) were surgical inpatients; 44% of which were at low risk for VTE, while 15%, 24%, and 17% were at moderate, high, and very high risk for VTE, respectively. Of the remaining 15,161,586 medical patients, 7,742,419 (51%) met ACCP VTE risk criteria. Over 12 million patients, comprising 31% of US hospital discharges in 2003, were at risk of VTE. Given the existence of internationally-accepted evidence-based guidelines for prevention of VTE, research is required to establish if this patient population is receiving recommended VTE prophylaxis.

Life-years gained from modern cardiological treatments and population risk factor changes in England and Wales, 1981-2000.

OBJECTIVES: We estimated life-years gained from cardiological treatments and cardiovascular risk factor changes in England and Wales between 1981 and 2000. METHODS: We used the IMPACT model to integrate data on the number of coronary heart disease patients, treatment uptake and effectiveness, risk factor trends, and median survival in coronary heart disease patients. RESULTS: Compared with 1981, there were 68230 fewer coronary deaths in 2000. Approximately 925415 life-years were gained among people aged 25-84 years (range: 745 195-1 138 655). Cardiological treatments for patients accounted for approximately 194145 life-years gained (range: 142505-259225), and population risk factor changes accounted for approximately 731270 life-years gained (range; 602695-879430). CONCLUSIONS: Modest reductions in major risk factors led to gains in life-years 4 times higher than did cardiological treatments. Effective policies to promote healthy diets and physical activity might achieve even greater gains.

Comparing estimates of cost effectiveness submitted to the National Institute for Clinical Excellence (NICE) by different organisations: retrospective study.

OBJECTIVE: To assess the association between different types of organisation and the results from economic evaluations. DESIGN: Retrospective pairwise comparison of evidence submitted to the technology appraisal programme of the National Institute for Clinical Excellence (NICE) by manufacturers of the relevant healthcare technologies and by contracted university based assessment groups. DATA SOURCES: Data from the first 62 appraisals. MAIN OUTCOME MEASURE: Incremental cost effectiveness ratios. RESULTS: Data from 27 of the 62 appraisals could be compared. The analysis of 54 pairwise comparisons showed that manufacturers' estimates of incremental cost effectiveness ratios were lower (suggesting a more cost effective use of resources) than those produced by the assessment groups (25 were lower, 29 were the same, none were higher, P < 0.01). Restriction of this dataset to include only one pairwise comparison per appraisal (27 pairs) produced a similar result (21 were lower, two were the same, four were higher, P < 0.001). CONCLUSIONS: The estimated incremental cost effectiveness ratios submitted by manufacturers were on average significantly lower than those submitted by the assessment groups. These results show that an important role of NICE's appraisal committee, and of decision makers in general, is to determine which economic evaluations, or parts of evaluations, should be given more credence.