Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Myocardial infarction and peripheral arterial disease: Treatment patterns and long-term outcome in men and women results from a Swedish nationwide study.

BACKGROUND: Differences in comorbidity, pharmacotherapy, cardiovascular (CV) outcome, and mortality between myocardial infarction (MI) patients and peripheral arterial disease (PAD) patients are not well documented. AIM: The aim of this study was to compare comorbidity, treatment patterns, CV outcome, and mortality in MI and PAD patients, focusing on sex differences. METHODS: This observational, population-based study used data retrieved from mandatory Swedish national registries. The risks of MI and death were assessed by Kaplan-Meier analysis. Secondary preventive drug use was characterized. Cox proportional risk hazard modelling was used to determine the risk of specific events. RESULTS: Overall, 91,808 incident MI patients and 52,408 PAD patients were included. CV mortality for MI patients at 12, 24, and 36 months after index was 12.3%, 19.3%, and 25.4%, and for PAD patients it was 15.5%, 23.4%, and 31.0%. At index, 89% of MI patients and 65% of PAD patients used aspirin and 74% and 53%, respectively, used statins. Unlike MI women, women with PAD had a lower rate of other CV-related comorbidities and a lower risk of CV events (age-adjusted hazard ratio 0.81, 95% confidence interval 0.79‒0.84), CV death (0.78, 0.75‒0.82), and all-cause death (0.78, 0.76‒0.80) than their PAD male counterparts. CONCLUSION: PAD patients were less intensively treated and had a higher CV mortality than MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI. This result indicates that the lower-limb vasculature may more often be the index site for atherosclerosis in women.

A clinician's experience of using the Cardiac Reader NT-proBNP point-of-care assay in a clinical setting.

UNLABELLED: The evaluation of natriuretic peptides has become increasingly valuable in a clinical setting, where information is often needed promptly. OBJECTIVES: To compare the usefulness of the recently released Roche Cardiac Reader NT-proBNP assay against the Roche Elecsys NT-proBNP laboratory system in a clinical setting. DESIGN AND RESULTS: Blood samples from 440 patients, who were either admitted with acute coronary syndromes or worsening heart failure, or who were heart failure outpatients, were evaluated. The relation between the two assays was analysed and the diagnostic concordance calculated. A good correlation was found between the assays (r=0.96, 95% CI: 0.94-0.97) with a diagnostic concordance of 93%. A separate analysis was performed in the range where most clinical decisions are made (60-3000 ng/L), with a diagnostic concordance of 88%. The usefulness in a clinical setting where time is important was high. CONCLUSION: The Roche Cardiac Reader NT-proBNP assay has been evaluated in a clinical setting. The point-of-care method shows good results, although with a restricted analytical range, compared with the reference.

Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy.

OBJECTIVE: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. METHODS: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. RESULTS: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. CONCLUSIONS: Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. TRIAL REGISTRATION NUMBER: NCT000391872.

The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model.

OBJECTIVE: To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG). DATA SOURCES: MEDLINE and EMBASE were searched from 1966 until 30 November 2008. REVIEW METHODS: We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model. RESULTS: We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario). CONCLUSIONS: Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.

Management of pancreatic pseudocysts.

Between 1969 and 1987, 68 patients with pancreatic pseudocysts were treated. The median cyst size was 10 cm (range 2-25 cm). Nine patients were managed conservatively with resolution of the pseudocyst occurring in eight patients. These patients had significantly smaller (median 4 cm) cysts compared with those in both percutaneously and surgically treated patients (P less than 0.01). In 22 patients the pseudocysts (median 9 cm) were punctured percutaneously under ultrasound guidance and the cyst fluid was aspirated or drained through a catheter. Complete resolution occurred in 13 patients after 1-4 (mean 1.8) punctures per patient, regression occurred in six patients after 1-4 (mean 2.0) puncture procedures per patient and three were unchanged. No complications were noted, except that two patients treated percutaneously required additional surgery. Thirty-seven patients were managed surgically (median cyst size 11 cm) with external drainage (12 patients), cystgastrostomy (17 patients), cystduodenostomy (three patients) cystjejunostomy (three patients) and pancreatic resection (two patients). Resolution of the cyst was noted in 29 patients, regression in five and three were unchanged. Five patients required additional surgery. Twelve complications were seen in ten patients (27 per cent), most frequently after external drainage. One patient died after surgical treatment. Mean hospital stay was 13 days among patients treated conservatively and 30 days in both percutaneously and surgically treated patients. Aspiration or catheter drainage of pseudocyst fluid guided by ultrasonography seems a safe and effective treatment of pancreatic pseudocysts and should be considered as initial therapy. If surgery is required cystgastrostomy is preferred.

Cost effectiveness of extended treatment with low molecular weight heparin (dalteparin) in unstable coronary artery disease: results from the FRISC II trial.

BACKGROUND: In unstable coronary artery disease short term treatment with low molecular weight heparin in addition to aspirin has been shown to be effective. OBJECTIVE: To assess the cost effectiveness of extended treatment with dalteparin in patients managed with a non-invasive treatment strategy. DESIGN: Prospective, randomised, multicentre study. SETTING: 58 centres in Sweden, Denmark, and Norway, of which 16 were interventional. PATIENTS: After at least five days' treatment with open label dalteparin, 2267 patients were randomised to continue double blind treatment with either subcutaneous dalteparin twice daily or placebo for three months. The patients' use of health service resources was recorded prospectively. MAIN OUTCOME MEASURE: Death/myocardial infarction. RESULTS: After one month into the double blind period there was a 47% relative reduction in death or myocardial infarction in the dalteparin group compared with the placebo group (p = 0.002). There was a non-significant mean cost difference, favouring the placebo group, of 849 Swedish crowns (SEK) per patient (equivalent to 58 pounds sterling). The incremental cost effectiveness ratio for giving dalteparin treatment for one month was SEK 30 300 (range -78 000 to 139 000) (2060 pounds sterling, range -5300 pounds sterling to pound 9400 pounds sterling) per avoided death or myocardial infarct. At three months, the decrease in death or myocardial infarction was not significant, precluding cost effectiveness analyses. CONCLUSIONS: There is a marginal and non-significant increase in costs for one month of extended dalteparin treatment compared with placebo. Extended dalteparin treatment lowers the risk of death or myocardial infarction in patients with unstable coronary artery disease. While in many countries the resources for early intervention are limited, extended dalteparin treatment up to one month is a cost effective bridge to invasive intervention.

Cost-effectiveness of an invasive strategy in unstable coronary artery disease; results from the FRISC II invasive trial. The Fast Revascularisation during InStability in Coronary artery disease.

AIMS: The utilization and timing of revascularization in unstable coronary artery disease varies, which could have important consequences for patients and for treatment costs. The FRISC II invasive trial compared an early invasive strategy vs a non-invasive strategy with respect to the composite end-point of death and myocardial infarction as well as costs. METHODS AND RESULTS: A total of 2457 patients, median age 66 years, comprising 70% men, were randomized. We prospectively recorded the patients' use of the health service. The results were analysed in a societal perspective. There was a significant 1.7% absolute reduction in deaths and a 3.7% absolute reduction in deaths and myocardial infarctions in the invasive compared to the non-invasive group after 12 months. During the initial hospitalization a patient in the invasive group spent on average 3.9 more days in hospital than a patient in the non-invasive group. Opposite results were found for rehospitalizations. The difference in mean total costs is SEK 23 876 (P<0.001). The incermental cost-effective ratio for choosing the invasive instead of the non-invasive strategy is SEK 1 404 000 per avoided death and SEK 645 000 per avoided death or myocardial infarction. CONCLUSION: The high cost at the beginning of the invasive strategy is substantial. The clinical results of the FRISC II study provided evidence that the invasive strategy reduces the rate of death and myocardial infarction in patients with unstable coronary artery disease. For policy discussions concerning whether or not to implement the invasive strategy, these positive results should be balanced against the cost-consequences of the strategy.