Can pro-brain-natriuretic peptide guided therapy of chronic heart failure...


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Title Can pro-brain-natriuretic peptide guided therapy of chronic heart failure reduce cardiovascular mortality and morbidity?
Period 2003 - unknown
Status Completed
Research number OND1298514


- BACKGROUND: Current chronic heart failure treatment strategies are still mainly implemented and adapted on the basis of clinical judgement, ignoring plasma neurohormone concentrations, although the latter are strong independent markers of cardiac status and prognosis. Brain natriuretic peptide (BNP) is a stress-induced cardiac hormone secreted from the ventricles in response to increased ventricular wall tension or stretch. BNP is directly proportional to ventricular volume expansion and pressure overload. Numerous studies show that concentrations of BNP and its stable precursor pro-BNP are the most powerful predictors of outcome in heart failure patients. BNP levels do often fall rapidly and significantly after successful treatment with diuretics and ACE-inhibitors. However, it remains unclear in which patients pro-BNP decreases, what target pro-BNP (general or individual) should be set for pro-BNP-titrated therapy, and whether such therapy effectively reduces heart failure related events. - HYPOTHESIS: We hypothesize that titration and adaptation of treatment targeted to an individually set plasma pro-BNP concentration in chronic heart failure patients is superior to empirical treatment based on clinical parameters alone. - AIM: The objective of the present study is to identify heart failure patients in whom pro-BNP decreases in response to therapy and to demonstrate that pro-BNP-titrated heart failure therapy leads to a significant reduction in mortality, morbidity (hospital re-admissions, necessity of intravenous therapy) and improvement in clinical condition among these patients. - METHODS: In total, 584 patients admitted to the hospital because of clinically decompensated heart failure will be included. After successful in-hospital treatment of congestion has led to a significant decrease in pro-BNP, the target pro-BNP is set at discharge. Patients will be subsequently randomized to a pro-BNP-titrated treatment group, in which therapy is aimed at achieving target pro-BNP values versus a clinical-titrated treatment group, in which treatment is guided by an objective heart failure scoring system solely. In both groups, outpatient heart failure pharmacotherapy is optimized according to protocols adhering to international guidelines. - EXPECTED RESULTS: By adding pro-BNP as guiding parameter, cardiovascular morbidity and mortality in patients with chronic heart failure will be reduced significantly. Thus, the present study will significantly alter current daily practice in the follow-up treatment of patients with heart failure. - OBJECTIVES: Primary objective of the present study is to identify heart failure patients in whom pro-BNP decreases in response to therapy and to demonstrate that pro-BNP-titrated heart failure therapy leads to a significant reduction in cardiovascular mortality and morbidity (hospital re-admissions, necessity of intravenous therapy) in these patients. Secondary objectives of the present study are: * To demonstrate within and between group effects of pro-BNP titrated therapy on secondary outcome measures such as final pro-BNP levels, patient quality of live (Minnesota Living with Heart Failure Questionnaire), patient exercise tolerance (ergometry), total mortality and morbidity, and Doppler echocardiographic parameters of systolic and diastolic LV function. * To assess whether primary and secondary outcome measures are exceedingly common in patients with elevated pro-BNP levels that are not responsive to pharmacological intervention. - RELEVANCE FOR CARDIOVASCULAR DISEASES: Congestive heart failure is a major public health problem with a high prevalence. Although its treatment has been greatly advanced, heart failure morbidity and mortality remain high. Heart failure drug treatment is complex, and questions remain as to how proven therapies should be implemented, and what the optimal dose is in individual patients. Currently, outpatient management of chronic congestive heart failure is dictated by clinical judgment, using symptoms and signs such as dyspnea, weight change, edema and jugular venous pressure. However, early detection of recurrent congestion is notoriously difficult. More objective parameters of cardiac and hemodynamic status such as plasma pro-brain natriuretic peptide (pro-BNP) might thus substantially improve heart failure follow-up. An increasing number of hospitals will be able to determine pro-BNP levels in the forthcoming years, with the associated costs. It is presently unknown whether routine determination of plasma pro-BNP will improve heart failure follow-up and outcome in terms of hospital re-admissions, morbidity and mortality. The present study is extremely relevant in addressing this question and will thereby have substantial influence on future outpatient heart failure care.

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Project leader Dr. D.J.W. van Kraaij
Project leader Prof.dr. Y.M. Pinto


D21300 Biochemistry
D21700 Physiology
D23220 Internal medicine
D24000 Health sciences

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