PMID- 14720012
OWN - NLM
STAT- MEDLINE
DCOM- 20040130
LR  - 20191108
IS  - 1175-6365 (Print)
IS  - 1175-6365 (Linking)
VI  - 2
IP  - 2
DP  - 2003
TI  - Prostanoids for pulmonary arterial hypertension.
PG  - 123-37
AB  - Pulmonary arterial hypertension (PAH) is a severe condition that markedly reduces 
      exercise capacity and survival in the affected patient population. PAH includes 
      primary pulmonary hypertension (PPH) and pulmonary hypertension associated with 
      collagen vascular diseases, congenital systemic-to-pulmonary shunts, portal 
      hypertension and HIV infection. All these conditions share virtually identical 
      obstructive pathologic changes of the pulmonary microcirculation and probably 
      similar pathobiologic processes. The pathophysiology is characterized by a 
      progressive increase in pulmonary vascular resistance, leading to right 
      ventricular failure and death. Prostacyclin is an endogenous substance that is 
      produced by vascular endothelial cells and induces vasodilatation, inhibition of 
      platelet activity, and antiproliferative effects. A dysregulation of prostacyclin 
      metabolic pathways has been shown in patients with PAH and this represents the 
      rationale for the exogenous therapeutic administration of this substance. The 
      clinical use of prostacyclin in patients with PAH has been made possible by the 
      synthesis of stable analogs that possess different pharmacokinetic properties but 
      share similar pharmacodynamic effects. Experience in humans has been initially 
      collected with epoprostenol, which is a synthetic salt of prostacyclin. 
      Epoprostenol has a short half-life in the circulation and requires continuous 
      administration by the intravenous route by means of infusion pumps and permanent 
      tunnelized catheters. In addition, epoprostenol is unstable at room temperature, 
      and the complex delivery system required is associated with several adverse 
      effects and potentially serious complications. For these reasons, alternatives to 
      intravenous epoprostenol have been sought and this has led to the development of 
      analogs that can be administered subcutaneously (treprostinil), orally (beraprost 
      sodium) or by inhalation (iloprost). Three unblinded clinical trials and several 
      uncontrolled trials have shown that treatment with epoprostenol improved symptoms 
      and exercise capacity in New York Heart Association (NYHA) class III and IV PAH 
      patients and also survival in patients with PPH. Subcutaneous treprostinil 
      improved symptoms, exercise, hemodynamics and clinical events in the largest 
      clinical trial ever performed in PAH, but local infusion site reactions limited 
      efficacy in a proportion of patients. Oral beraprost sodium improved exercise 
      capacity only in patients with PPH and is the only prostacyclin analog that has 
      also been tested in NYHA class II patients. Inhaled iloprost has improved 
      symptoms, exercise capacity and clinical events in patients with PAH and 
      inoperable chronic thromboembolic pulmonary hypertension. The favorable effects 
      of prostanoids observed in all studies coupled with different profiles of adverse 
      events and tolerability for each prostacyclin analog allow the unique opportunity 
      to select the most appropriate compound for the individual patient with PAH.
FAU - Galie, Nazzareno
AU  - Galie N
AD  - Institute of Cardiology, University of Bologna, Bologna, Italy. 
      n.galie@bo.nettuno.it
FAU - Manes, Alessandra
AU  - Manes A
FAU - Branzi, Angelo
AU  - Branzi A
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Am J Respir Med
JT  - American journal of respiratory medicine : drugs, devices, and other 
      interventions
JID - 101132974
RN  - 0 (Prostaglandins)
SB  - IM
MH  - Adult
MH  - Age Distribution
MH  - Aged
MH  - *Cause of Death
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/diagnosis/*drug therapy/*mortality
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Prostaglandins/*administration & dosage/adverse effects
MH  - Randomized Controlled Trials as Topic
MH  - Risk Assessment
MH  - Severity of Illness Index
MH  - Sex Distribution
MH  - Survival Analysis
MH  - Treatment Outcome
RF  - 118
EDAT- 2004/01/15 05:00
MHDA- 2004/01/31 05:00
CRDT- 2004/01/15 05:00
PHST- 2004/01/15 05:00 [pubmed]
PHST- 2004/01/31 05:00 [medline]
PHST- 2004/01/15 05:00 [entrez]
AID - 223 [pii]
AID - 10.1007/BF03256644 [doi]
PST - ppublish
SO  - Am J Respir Med. 2003;2(2):123-37. doi: 10.1007/BF03256644.