Prognostic value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein as a marker for major cardiac events in asymptomatic individuals: a health technology assessment report.

OBJECTIVES: The aim of this study was to compare the predictive value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein (hs-CRP)-screening in addition to traditional risk factor screening in apparently healthy persons as a means of preventing coronary artery disease. METHODS AND RESULTS: The systematic review was performed according to internationally recognized methods. Seven studies on risk prediction, one clinical decision-analytic modeling study, and three decision-analytic cost-effectiveness studies were included. The adjusted relative risk of high hs-CRP-level ranged from 0.7 to 2.47 (p < .05 in four of seven studies). Adding hs-CRP to the prediction models increased the areas under the curve by 0.00 to 0.027. Based on the clinical decision analysis, both individuals with elevated hs-CRP-levels and those with hyperlipidemia have a similar gain in life expectancy following statin therapy. One high-quality economic modeling study suggests favorable incremental cost-effectiveness ratios for persons with elevated hs-CRP and higher risk. However, many model parameters were based on limited evidence. CONCLUSIONS: Adding hs-CRP to traditional risk factors improves risk prediction, but the clinical relevance and cost-effectiveness of this improvement remain unclear.

Deterministic sensitivity analysis for first-order Monte Carlo simulations: a technical note.

OBJECTIVES: Monte Carlo microsimulations have gained increasing popularity in decision-analytic modeling because they can incorporate discrete events. Although deterministic sensitivity analyses are essential for interpretation of results, it remains difficult to combine these alongside Monte Carlo simulations in standard modeling packages without enormous time investment. Our purpose was to facilitate one-way deterministic sensitivity analysis of TreeAge Markov state-transition models requiring first-order Monte Carlo simulations. METHODS AND RESULTS: Using TreeAge Pro Suite 2007 and Microsoft Visual Basic for EXCEL, we constructed a generic script that enables one to perform automated deterministic one-way sensitivity analyses in EXCEL employing microsimulation models. In addition, we constructed a generic EXCEL-worksheet that allows for use of the script with little programming knowledge. CONCLUSIONS: Linking TreeAge Pro Suite 2007 and Visual Basic enables the performance of deterministic sensitivity analyses of first-order Monte Carlo simulations. There are other potentially interesting applications for automated analysis.

Utility estimates for decision-analytic modeling in chronic heart failure--health states based on New York Heart Association classes and number of rehospitalizations.

OBJECTIVES: For economic evaluations of chronic heart failure (CHF) management strategies, utilities are not currently available for disease proxies commonly used in Markov models. Our objective was to estimate utilities for New York Heart Association (NYHA) classification and number of cardiovascular rehospitalizations. METHODS: EuroQol 5D data from the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study trial were used to estimate utilities as a function of NYHA classification and number of cardiovascular rehospitalizations. RESULTS: In multivariate regression analyses adjusted for age (60 years), female sex and absence of further comorbidities, utilities for NYHA classes I-IV were 0.90, 0.83, 0.74, and 0.60 (P-value < 0.001 for trend). For cardiovascular rehospitalizations 0, 1, 2 and >or=3, the associated utilities were 0.88, 0.85, 0.84, and 0.82 (P-value < 0.001 for trend). CONCLUSIONS: NYHA class and number of cardiovascular rehospitalizations are established proxies for CHF progression and can be linked to utilities when used as health states in a Markov model. NYHA class should be used when feasible.

Decision-analytic evaluation of the clinical effectiveness and cost-effectiveness of management programmes in chronic heart failure.

BACKGROUND AND AIMS: While management programmes (MPs) for chronic heart failure (CHF) are clinically effective, their cost-effectiveness remains uncertain. Thus, this study sought to determine the cost-effectiveness of MPs. METHODS AND RESULTS: We developed a Markov model to estimate life expectancy, quality-adjusted life expectancy, lifetime costs, and the incremental cost-effectiveness of MPs as compared to standard care. Standard care was defined by the EuroHeart Failure Survey for Germany, MP efficacy was derived from our recent meta-analysis and cost estimates were based on the German healthcare system. For a population with a mean age 67 years (35% female) at onset of CHF, our model predicted an average quality-adjusted life expectancy of 2.64 years for standard care and 2.83 years for MP. MP yielded additional lifetime costs of euro1700 resulting in an incremental cost-utility ratio (ICUR) of euro8900 (95% CI: dominant to 177,100) per quality-adjusted life year (QALY) gained. Sensitivity analyses demonstrated that the ICUR was sensitive to age and sex. CONCLUSION: MPs increase life expectancy in patients with CHF by an average of 84 days and increase lifetime cost of care by approximately euro1700. MPs improve outcomes in a cost-effective manner, although they are not cost-saving on a lifetime horizon.

A systematic meta-analysis of the efficacy and heterogeneity of disease management programs in congestive heart failure.

BACKGROUND: We sought to systematically combine the evidence on efficacy of disease management programs (DMPs) in the treatment of congestive heart failure (CHF), to identify and explain heterogeneity of results from prior studies of DMPs, and to assess potential publication bias from these studies. METHODS AND RESULTS: We conducted a systematic literature search on randomized clinical trials investigating the effect of DMPs on CHF outcomes and performed meta-analyses and meta-regressions comparing DMPs and standard care for mortality and rehospitalization. We included 36 studies from 13 different countries (with data from 8341 patients). Our meta-analysis yielded a pooled risk difference of 3% (95% confidence interval [CI] 1-6%, P < .01) for mortality and of 8% (95% CI 5-11%, P < .0001) for rehospitalization, both favoring DMP. Factors explaining heterogeneity between studies included severity of disease, proportion of beta-blocker at baseline, country, duration of follow-up, and mode of postdischarge contact. No statistically significant publication bias was detected. CONCLUSION: DMPs have the potential to reduce morbidity and mortality for patients with CHF. The benefit of the intervention depends on age, severity of disease, guideline-based treatment at baseline, and DMP modalities. Future studies should directly compare the effect of different aspects of disease management programs for different populations.

A network against failing hearts--introducing the German "Competence Network Heart Failure".

Heart failure (HF) has been identified as one of the most threatening diseases for the western civilisation, posing a risk to health for a rising number of patients. Acknowledging the medical problem of HF to be both economically and socially threatening the German Federal Ministry of Research and Education (BMBF) initiated a nationwide research network aiming to find new ways in prevention, alleviation and treatment of the widespread disease. The "Competence Network Heart Failure" (CNHF), initiated in 2003, bundles the scientific expertise in a large-scale research network; its aims are the coordination of basic and applied clinical research as well as dissemination of findings into clinical practice in order to consolidate and perpetuate the achieved improvements. The scope of this paper is to introduce the CNHF and to provide an overview of the tasks and hitherto attained achievements to a broad spectrum of health care providers.

[Prognostic value and clinical effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events]. / Prognostische Wertigkeit und klinische Effektivität des hochsensitiven C-reaktiven Proteins als Marker in der Primärprävention der koronaren Herzkrankheit.

OBJECTIVE: To compare the predictive value and the clinical effectiveness of additional high sensitivity C-reactive protein (hs-CRP) screening as opposed to traditional risk factor screening alone as a strategy of primary prevention of coronary artery disease (CAD). METHODS: Following a comprehensive search of 26 electronic databases by DAHTA DIMDI, a systematic review was performed in accordance with international standards of evidence based medicine. Eight publications on risk prediction and one study addressing clinical decision-analytic modelling were included in the assessment. RESULTS: The adjusted relative risk of a high hs-CRP level (> 3 mg/L) for myocardial infarction, cardiac related death, and cardiovascular events ranged from 0.7 to 2.47 (p < 0.05 in 4 of 7 studies). The area under the receiver operating characteristic curve (AUC) increased by 0.00 to 0.027 when hs-CRP was added to the prediction models (4 of 7 studies statistically significant with p < 0.05). Based on a published decision-analytic model examining hs-CRP screening, the gain in life expectancy due to statin therapy in individuals with elevated hs-CRP was similar when compared to patients with hyperlipidaemia. Nonetheless, evidence on many model parameters was limited. CONCLUSION: Screening with hs-CRP in addition to traditional risk factors improves risk prediction. However, the incremental effect is moderate and the clinical relevance remains unclear.

Prognostic value, clinical effectiveness and cost-effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events.

BACKGROUND: In a substantial portion of patients (= 25%) with coronary heart disease (CHD), a myocardial infarction or sudden cardiac death without prior symptoms is the first manifestation of disease. The use of new risk predictors for CHD such as the high-sensitivity C-reactive Protein (hs-CRP) in addition to established risk factors could improve prediction of CHD. As a consequence of the altered risk assessment, modified preventive actions could reduce the number of cardiac death and non-fatal myocardial infarction. RESEARCH QUESTION: Does the additional information gained through the measurement of hs-CRP in asymptomatic patients lead to a clinically relevant improvement in risk prediction as compared to risk prediction based on traditional risk factors and is this cost-effective? METHODS: A literature search of the electronic databases of the German Institute of Medical Documentation and Information (DIMDI) was conducted. Selection, data extraction, assessment of the study-quality and synthesis of information was conducted according to the methods of evidence-based medicine. RESULTS: Eight publications about predictive value, one publication on the clinical efficacy and three health-economic evaluations were included. In the seven study populations of the prediction studies, elevated CRP-levels were almost always associated with a higher risk of cardiovascular events and non-fatal myocardial infarctions or cardiac death and severe cardiovascular events. The effect estimates (odds ratio (OR), relative risk (RR), hazard ratio (HR)), once adjusted for traditional risk factors, demonstrated a moderate, independent association between hs-CRP and cardiac and cardiovascular events that fell in the range of 0.7 to 2.47. In six of the seven studies, a moderate increase in the area under the curve (AUC) could be detected by adding hs-CRP as a predictor to regression models in addition to established risk factors though in three cases this was not statistically significant. The difference [in the AUC] between the models with and without hs-CRP fell between 0.00 and 0.023 with a median of 0.003. A decision-analytic modeling study reported a gain in life-expectancy for those using statin therapy for populations with elevated hs-CRP levels and normal lipid levels as compared to statin therapy for those with elevated lipid levels (approximately 6.6 months gain in life-expectancy for 58 year olds). Two decision-analytic models (three publications) on cost-effectiveness reported incremental cost-effectiveness ratios between Euro 8,700 and 50,000 per life year gained for the German context and between 52,000 and 708,000 for the US context. The empirical input data for the model is highly uncertain. CONCLUSION: No sufficient evidence is available to support the notion that hs-CRP-values should be measured during the global risk assessment for CAD or cardiovascular disease in addition to the traditional risk factors. The additional measurement of the hs-CRP-level increases the incremental predictive value of the risk prediction. It has not yet been clarified whether this increase is clinically relevant resulting in reduction of cardiovascular morbidity and mortality. For people with medium cardiovascular risk (5 to 20% in ten years) additional measurement of hs-CRP seems most likely to be clinical relevant to support the decision as to whether or not additional statin therapy should be initiated for primary prevention. Statin therapy can reduce the occurrence of cardiovascular events for asymptomatic individuals with normal lipid and elevated hs-CRP levels. However, this is not enough to provide evidence for a clinical benefit of hs-CRP-screening. The cost-effectiveness of general hs-CRP-screening as well as screening among only those with normal lipid levels remains unknown at present.