Surrogate end points for pulmonary arterial hypertension

• Published in: The American heart journal Vol. 148; no. 4; pp. 559 - 565
• Main Authors: Kawut, Steven M., Palevsky, Harold I.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2004; Elsevier; Elsevier Limited
• Subjects: Biological and medical sciences; Biomarkers - blood; Clinical trials; Disease; Drug therapy; Echocardiography; Exercise Test; FDA approval; Hemodynamics; Humans; Hypertension; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - therapy; Medical sciences; Neurotransmitter Agents - blood; Outcome Assessment (Health Care) - methods; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Quality of life; Regulatory approval; Studies; Cardiovascular disease; End; Respiratory disease; Artery; Pulmonary hypertension
• DOI: 10.1016/j.ahj.2004.04.017
• ISSN: 0002-8703; 1097-6744

Pulmonary arterial hypertension is a rare disease that is characterized by increased pulmonary vascular resistance and right heart failure. Recent advances in the understanding of pulmonary arterial hypertension have been translated into effective therapies tested in clinical trials. These trials have used surrogate end points as the primary outcomes of interest. However, it is not clear which potential surrogate end points are reliable and valid for studying pulmonary arterial hypertension. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Hemodynamic, echocardiographic, neurohormone, and exercise measures hold some promise as potential surrogate end points for clinical trials of therapy for pulmonary arterial hypertension. Hemodynamic measures have the most evidence to support their use. Functional studies, such as the distance walked in 6 minutes, also may be meaningful. We present the available data as well as the strengths and weaknesses of each metric. Further studies should focus on validating the most promising of these surrogate end points, so that future investigators, subjects, and patients may benefit from the advantages they confer on clinical trials and patient care.