Testing new targets of therapy in advanced heart failure: The design and rationale of the Strategies for Tailoring Advanced Heart Failure Regimens in the Outpatient Setting: BRain NatrIuretic Peptide Versus the Clinical CongesTion ScorE (STARBRITE) trial

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition.Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction b 30%, pseudonormal or restrictive mitral inflow pattern at Dopplerechocardiography; high left and/or right ventricular filling pressures; elevated B-type natriuretic peptides; 4) severe impairment of functional capacity demonstrated by either inability to exercise, a 6-minute walk test distance b 300 m or a peak oxygen uptake b 12-14 ml/kg/min; 5) history of N1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy. This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events. These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives.

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“…BNP or NTproBNP may be useful to assess prognosis and to tailor therapy. This hypothesis is currently being tested in randomised trials [26,27].…”

Section: Natriuretic Peptides and Other Biomarkersmentioning

confidence: 99%

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Metra

Ponikowski²,

Dickstein

et al. 2007

European J of Heart Fail

353

242

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“…Patients would be randomized either to serial surrogate measurements with explicit therapeutic algorithms based on the results or to traditional care; such RCTs of surrogate-end point guided therapy are only recently being performed in CHF [25][26][27]. Without supportive evidence showing the incremental benefit of using goal-directed therapy, a surrogate end point-guided approach could result in significant overuse or underuse of therapies to the detriment of patients with PAH.…”

Section: Validating a Surrogate-guided Therapeutic Approachmentioning

confidence: 99%

“…The weaknesses of some biomarkers lie in their within-subject variability, which may be substantial, and the potential for therapies to directly affect them (endothelin receptor antagonists and endothelin-1, for example). RCTs demonstrating improvement in outcomes with the use of a biomarker-guided strategy is necessary before incorporating routine BNP or other measures into clinical practice in PAH [25][26][27].…”

Section: Plasma Biomarkersmentioning

confidence: 99%

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Snow¹,

Kawut²

2007

Clinics in Chest Medicine

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Pulmonary arterial hypertension (PAH) is a rare disease which is characterized by increased pulmonary vascular resistance and right heart failure. Recent discoveries in disease pathophysiology have been translated into effective therapies tested in clinical trials. The studies which have led to the regulatory board approval of therapies for PAH have focused on surrogate and intermediate end points, thought to reflect quantity and quality of life, respectively. However, validation of many of these surrogates is incomplete. It is also unknown which indicators of function or long-term survival should be used to formulate decisions regarding addition, discontinuation, or combination of therapies. Identification of suitable end points would therefore not only help investigators design appropriate clinical trials, but also assist clinicians in caring for patients with PAH. Hemodynamic, cardiac imaging, plasma biomarkers, and exercise testing hold some promise as potential surrogate end points for PAH. Functional status and quality of life assessments may also have important roles. Future studies should validate the most promising surrogate markers, so that patients, clinicians, subjects, and investigators may benefit from the advantages they confer on clinical care and on clinical trials.The past several years have yielded an explosion of randomized clinical trials (RCTs) of several new medical therapies for pulmonary arterial hypertension (PAH). The hopes for these and all treatments for potentially fatal diseases are 1) to improve how a patient feels or functions and/ or 2) to prolong survival. While simply stated, the assessment of progress towards these goals may be quite complex [1][2][3][4][5][6].New PAH therapies have gained regulatory board approval based on studies with intermediate and surrogate end points as primary outcomes, believed to reflect the impact of these drugs on quality of life (QOL) and survival, respectively. While hemodynamic, plasma, cardiac imaging, exercise, functional, and QOL parameters are promising candidates, the reliability and validity of these measures are not clearly established. In addition, there are no RCTs addressing the use of such end points in guiding management decisions in PAH, such as changing, intensifying, escalating, or combining therapies. Despite this lack of evidence, clinicians who

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“…141 However, neutral results were also observed when a natriuretic peptide-guided approach was compared with standard clinical assessment. 142,143 Therefore, the concept of natriuretic peptide-guided management of heart failure is still being debated, and there is no general consensus in expert opinion regarding this issue. Another potential use of blood natriuretic peptide testing in treatment monitoring is the assessment of adequacy of therapy in decompensated heart failure.…”

Section: A Monitoring Therapy Using Bnp or Nt-probnp Guidancementioning

confidence: 99%

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure

Christenson¹,

Apple²,

Cannon³

et al. 2007

Circulation

206

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Testing new targets of therapy in advanced heart failure: The design and rationale of the Strategies for Tailoring Advanced Heart Failure Regimens in the Outpatient Setting: BRain NatrIuretic Peptide Versus the Clinical CongesTion ScorE (STARBRITE) trial

Cited by 47 publications

References 30 publications

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure

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