Pulmonary Hypertension, January 2007
Pulmonary Hypertension, January 2007
The Pulmonary Hypertension Journal Scan is the clinician's guide to the latest clinical research findings from JAMA, The New England Journal of Medicine, CHEST, and other journals of interest. Short summaries of feature articles include links to the article abstracts when available. (Access to full-text articles usually requires registration at the specific journal's Web site.)
Barst RJ, Galie N, Naeije R, et al.
European Respiratory Journal. 2006:28;1195-1203
Untreated idiopathic pulmonary arterial hypertension (IPAH), formerly known as primary pulmonary hypertension, carries with it a median survival of 2.8 years. Treprostinil is a prostacyclin analogue that was approved by the US Food and Drug Administration (FDA) as a therapy for this deadly condition in 2002. It was initially approved for subcutaneous (SQ) administration, but has since also received approval for intravenous delivery. Barst and colleagues assessed the long-term benefits of chronic subcutaneous treprostinil in a group of 860 patients who received this as initial therapy. These study participants included 496 patients who had previously been enrolled in 3 placebo-controlled studies of SQ treprostinil and who were subsequently continued on open-label drug. The remaining patients were started on open-label treprostinil de novo.
The mean age of the group was 46 years. The study group was predominantly female (76%) and white (83%). The cohort included patients with IPAH (48%), Eisenmenger's physiology (21%), and diffuse systemic sclerosis (8%). Of the 860 patients, 506 (59%) discontinued the drug prematurely for various reasons; 136 died, 11 received transplants, 117 had clinical deterioration requiring/not requiring rescue therapy, 29 withdrew consent, 199 had an adverse event, 10 had protocol violations, and 4 were lost to follow-up. Most of those who dropped out did so within the first year of therapy.
With regard to adverse events, 196 of 199 patients reported infusion-site pain or reactions. The most pertinent drug-specific/delivery-specific side effects were pain at the infusion site and site reaction, which were reported by 92% and 81% of the patients, respectively. There were no reports of gram-negative sepsis.
Of the patients requiring concomitant or alternative PAH medications: 98 had converted to alternative prostacyclin analogues, 105 patients (12%) received bosentan add-on therapy, and 25 (3%) received sildenafil. The number of patients who completed annual milestones of therapy included 538 at the 1-year interval (63%), 312 after 2 years (36%), 135 after 3 years (17%), and 13 after 4 years (2%). The median doses of SQ treprostinil at these time points were 26, 36, 42, and 42 ng/kg/min, respectively. The survival rates at the same time intervals were 87%, 78%, 71%, and 68%, respectively. Survival was similar for those patients who were continued on treprostinil monotherapy only. For the IPAH subgroup in whom hemodynamic data were available (n = 332), the survival rates were 91%, 82%, 76%, and 72% at 1, 2, 3 and 4 years, respectively. This compares favorably to the projected survival (based on the National Institutes of Health [NIH] formula) without therapy of 69%, 5%, 46%, and 38%, respectively. Survival rates also differed according to baseline New York Heart Association (NYHA) class; for NYHA class II, the survival rates were 91%, 84%, 79%, and 74%, respectively; for class II, the rates were a little lower at 88%, 79%, 72%, and 70%; and for class IV patients, survival rates were 71% at 1 year, 62% at 2 years, and 52% at 3 years.
This study suffers the same limitation that all recent studies assessing survival in PAH do. Specifically, survival rates have to be compared to historical controls and/or the projected survival based on the "aging" NIH prediction formula. With this caveat, it does nonetheless appear that SQ treprostinil is a reasonable alternative as first-line therapy in cases where it is deemed necessary as a parenteral prostanoid agent. Survival rates are similar to those previously reported in studies of intravenous epoprostenol. Not surprisingly, the major drawback remains that of infusion-site pain, which can necessitate the discontinuation of therapy in up to a quarter of patients.
The Pulmonary Hypertension Journal Scan is the clinician's guide to the latest clinical research findings from JAMA, The New England Journal of Medicine, CHEST, and other journals of interest. Short summaries of feature articles include links to the article abstracts when available. (Access to full-text articles usually requires registration at the specific journal's Web site.)
Barst RJ, Galie N, Naeije R, et al.
European Respiratory Journal. 2006:28;1195-1203
Untreated idiopathic pulmonary arterial hypertension (IPAH), formerly known as primary pulmonary hypertension, carries with it a median survival of 2.8 years. Treprostinil is a prostacyclin analogue that was approved by the US Food and Drug Administration (FDA) as a therapy for this deadly condition in 2002. It was initially approved for subcutaneous (SQ) administration, but has since also received approval for intravenous delivery. Barst and colleagues assessed the long-term benefits of chronic subcutaneous treprostinil in a group of 860 patients who received this as initial therapy. These study participants included 496 patients who had previously been enrolled in 3 placebo-controlled studies of SQ treprostinil and who were subsequently continued on open-label drug. The remaining patients were started on open-label treprostinil de novo.
The mean age of the group was 46 years. The study group was predominantly female (76%) and white (83%). The cohort included patients with IPAH (48%), Eisenmenger's physiology (21%), and diffuse systemic sclerosis (8%). Of the 860 patients, 506 (59%) discontinued the drug prematurely for various reasons; 136 died, 11 received transplants, 117 had clinical deterioration requiring/not requiring rescue therapy, 29 withdrew consent, 199 had an adverse event, 10 had protocol violations, and 4 were lost to follow-up. Most of those who dropped out did so within the first year of therapy.
With regard to adverse events, 196 of 199 patients reported infusion-site pain or reactions. The most pertinent drug-specific/delivery-specific side effects were pain at the infusion site and site reaction, which were reported by 92% and 81% of the patients, respectively. There were no reports of gram-negative sepsis.
Of the patients requiring concomitant or alternative PAH medications: 98 had converted to alternative prostacyclin analogues, 105 patients (12%) received bosentan add-on therapy, and 25 (3%) received sildenafil. The number of patients who completed annual milestones of therapy included 538 at the 1-year interval (63%), 312 after 2 years (36%), 135 after 3 years (17%), and 13 after 4 years (2%). The median doses of SQ treprostinil at these time points were 26, 36, 42, and 42 ng/kg/min, respectively. The survival rates at the same time intervals were 87%, 78%, 71%, and 68%, respectively. Survival was similar for those patients who were continued on treprostinil monotherapy only. For the IPAH subgroup in whom hemodynamic data were available (n = 332), the survival rates were 91%, 82%, 76%, and 72% at 1, 2, 3 and 4 years, respectively. This compares favorably to the projected survival (based on the National Institutes of Health [NIH] formula) without therapy of 69%, 5%, 46%, and 38%, respectively. Survival rates also differed according to baseline New York Heart Association (NYHA) class; for NYHA class II, the survival rates were 91%, 84%, 79%, and 74%, respectively; for class II, the rates were a little lower at 88%, 79%, 72%, and 70%; and for class IV patients, survival rates were 71% at 1 year, 62% at 2 years, and 52% at 3 years.
This study suffers the same limitation that all recent studies assessing survival in PAH do. Specifically, survival rates have to be compared to historical controls and/or the projected survival based on the "aging" NIH prediction formula. With this caveat, it does nonetheless appear that SQ treprostinil is a reasonable alternative as first-line therapy in cases where it is deemed necessary as a parenteral prostanoid agent. Survival rates are similar to those previously reported in studies of intravenous epoprostenol. Not surprisingly, the major drawback remains that of infusion-site pain, which can necessitate the discontinuation of therapy in up to a quarter of patients.
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