Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension.
The numerous controlled clinical trials performed recently in pulmonary arterial hypertension (PAH) can allow us to abandon a clinical-based treatment strategy and adopt an evidence-based therapy. Both uncontrolled and controlled clinical trials with different compounds and procedures are reviewed and compared in order to define the efficacy-to-side-effect ratio of each treatment. A grading system for the level of evidence of treatments based on the number of favorable controlled clinical trials performed with a given compound is adopted; a treatment algorithm based on the evidence derived by clinical trials is proposed. It includes drugs approved by regulatory agencies for the treatment of patients with PAH and/or drugs available on the market for other indications. The algorithm is restricted to patients in New York Heart Association (NYHA) functional class III or IV because they represent the largest population included in controlled clinical trials. In addition, the different treatments have been evaluated mainly in sporadic, idiopathic PAH and in PAH associated with scleroderma or to anorexigen use. Extrapolation of these recommendations to the other PAH subgroups should be done with caution. Oral anticoagulation is proposed for all patients, whereas diuretic treatment and supplemental oxygen are indicated in cases of fluid retention and hypoxemia, respectively. High doses of calcium channel blockers are indicated only in the minority of patients who are responders to acute vasoreactivity testing. Nonresponders to acute vasoreactivity testing, or responders who remain in NYHA functional class III, should be considered candidates for treatment with either an endothelin receptor antagonist or a prostanoid. Continuous intravenous administration of epoprostenol is proposed as rescue treatment in NYHA functional class IV patients. Phosphodiesterase-V inhibitors should be considered in patients who have failed or are not candidates to other therapies. Combination therapy can be attempted in selected cases. Both balloon atrial septostomy and lung transplantation are indicated for refractory patients or where medical treatment is unavailable.
Galiè
Nazzareno
N
Institute of Cardiology, University of Bologna, Bologna, Italy. n.galie@bo.nettuno.it
Seeger
Werner
W
Naeije
Robert
R
Simonneau
Gerald
G
Rubin
Lewis J
LJ
D000465:Algorithms; D002986:Clinical Trials as Topic; D019317:Evidence-Based Medicine; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology / Q000628:therapy*; D011651:Pulmonary Artery / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome