See clinical trial results for patients who received continuous intravenous (IV) epoprostenol plus conventional therapy*
*Compared to those who received conventional therapy alone.
Study Design
Epoprostenol was studied in 2 prospective, open-label, randomized trials of 8 and 12 weeks duration (pooled data results) in patients with idiopathic pulmonary arterial hypertension (IPAH) or heritable PAH (HPAH). Patients were New York Heart Association (NYHA) Functional Class III or IV, except for 2 patients who were NYHA Functional Class II.
Epoprostenol plus conventional therapy
(n=52)†
Conventional therapy alone
(n=54)†
Dosage of epoprostenol was determined as described under dosage and administration and averaged 9.2 ng/kg/min at study's end. In the 12-week, open-label, randomized, parallel study:
| • | The primary endpoint was a change from baseline in exercise capacity as measured by the 6-Minute Walk Test |
| • | Other major study objectives included the effect of epoprostenol on survival and quality of life (using the Chronic Heart Failure Questionnaire, the Nottingham Health Profile, and the Dyspnea-Fatigue Rating) |
| • | The authors also evaluated the effects of epoprostenol on hemodynamics1 |
Exercise Data in
IPAH/HPAH at 12 weeks
Statistically significant improvement was observed in exercise capacity, as measured by the 6-Minute Walk Test
Improvements were apparent as early as the first week of therapy
Dyspnea and Fatigue Data in IPAH/HPAH
Increases in exercise capacity were accompanied by statistically significant improvement in dyspnea and fatigue.‡
‡Measured by the Chronic Heart Failure Questionnaire and the Dyspnea Fatigue Index.
Survival Data in IPAH/HPAH at 12 weeks
None of the 41 patients receiving epoprostenol died.
8 of 40 (20%) patients receiving conventional therapy alone died (P=0.003).
At the end of the treatment (12 weeks)2:
No statistical difference in survival was observed in patients with PAH associated with scleroderma spectrum of diseases (PAH-SSD).
| Baseline Values | Mean Change From Baseline at End of Treatment Period§ | |||
|---|---|---|---|---|
| Parameter | Epoprostenol Plus Conventional Therapy (n=52) | Conventional Therapy Alone (n=54) | Epoprostenol Plus Conventional Therapy (n=48) | Conventional Therapy Alone (n=41) |
| CI (L/min/m2) | 2.0 | 2.0 | 0.3|| | -0.1 |
| mPAP (mmHg) | 60 | 60 | -5|| | 1 |
| PVR (Wood units) | 16 | 17 | -4|| | 1 |
| mSAP (mmHg) | 89 | 91 | -4 | -3 |
| SV (mL/beat) | 44 | 43 | 6|| | -1 |
| TPR (Wood units) | 20 | 21 | -5|| | 1 |
| Baseline Values | |
|---|---|
| CI (L/min/m2) | |
| Epoprostenol Plus Conventional Therapy (n=52) | 2.0 |
| Conventional Therapy Alone (n=54) | 2.0 |
| mPAP (mmHg) | |
| Epoprostenol Plus Conventional Therapy (n=52) | 60 |
| Conventional Therapy Alone (n=54) | 60 |
| PVR (Wood units) | |
| Epoprostenol Plus Conventional Therapy (n=52) | 16 |
| Conventional Therapy Alone (n=54) | 17 |
| mSAP (mmHg) | |
| Epoprostenol Plus Conventional Therapy (n=52) | 89 |
| Conventional Therapy Alone (n=54) | 91 |
| SV (mL/beat) | |
| Epoprostenol Plus Conventional Therapy (n=52) | 44 |
| Conventional Therapy Alone (n=54) | 43 |
| TPR (Wood units) | |
| Epoprostenol Plus Conventional Therapy (n=52) | 20 |
| Conventional Therapy Alone (n=54) | 21 |
| Mean Change From Baseline at End of Treatment Period§ | |
|---|---|
| CI (L/min/m2) | |
| Epoprostenol Plus Conventional Therapy (n=48) | 0.3|| |
| Conventional Therapy Alone (n=41) | -0.1 |
| mPAP (mmHg) | |
| Epoprostenol Plus Conventional Therapy (n=48) | -5|| |
| Conventional Therapy Alone (n=41) | 1 |
| PVR (Wood units) | |
| Epoprostenol Plus Conventional Therapy (n=48) | -4|| |
| Conventional Therapy Alone (n=41) | 1 |
| mSAP (mmHg) | |
| Epoprostenol Plus Conventional Therapy (n=48) | -4 |
| Conventional Therapy Alone (n=41) | -3 |
| SV (mL/beat) | |
| Epoprostenol Plus Conventional Therapy (n=48) | 6|| |
| Conventional Therapy Alone (n=41) | -1 |
| TPR (Wood units) | |
| Epoprostenol Plus Conventional Therapy (n=48) | -5|| |
| Conventional Therapy Alone (n=41) | 1 |
CI: cardiac index; mPAP: mean pulmonary arterial pressure; mSAP: mean systemic arterial pressure; PVR: pulmonary vascular resistance; SV: stroke volume; TPR: total pulmonary resistance. §At 8 weeks: epoprostenol n=10, conventional therapy n=11 (n is the number of patients with hemodynamic data). At 12 weeks: epoprostenol n=38, conventional therapy n=30 (n is the number of patients with hemodynamic data). ||Denotes statistically significant difference between epoprostenol and conventional therapy groups.
Epoprostenol plus conventional therapy¶
Increase
| • | Cardiac Index by 15% |
| • | Stroke Volume by 14% |
Decrease
| • | Mean Pulmonary Arterial Pressure by 8% |
| • | Pulmonary Vascular Resistance by 25% |
| • | Total Pulmonary Resistance by 25% |
Hemodynamic Data in IPAH/HPAH
There was significant improvement in hemodynamics for patients who received chronic continuous infusions of epoprostenol plus conventional therapy compared to patients who received conventional therapy alone.
The most common and dose-limiting adverse events during dose initiation and escalation (≥1%) were:
| • | Flushing (58%) |
| • | Headache (49%) |
| • | Nausea/vomiting (32%) |
| • | Hypotension (16%) |
| • | Anxiety/nervousness/agitation (11%) |
| • | Chest pain (11%) |
| • | Dizziness (8%) |
| • | Bradycardia (5%) |
| • | Abdominal pain (5%) |
| • | Musculoskeletal pain (3%) |
| • | Dyspnea (2%) |
| • | Back pain (2%) |
| • | Sweating, dyspepsia, hypesthesia/paresthesia, tachycardia (1%), respectively |
Adverse events occurring in patients with idiopathic or heritable PAH with ≥10% difference between epoprostenol and conventional therapy alone were:
| • | Chills/fever/sepsis/flu-like symptoms (25% vs 11%) |
| • | Tachycardia (35% vs 24%) |
| • | Flushing (42% vs 2%) |
| • | Diarrhea (37% vs 6%) |
| • | Nausea/vomiting (67% vs 48%) |
| • | Jaw pain (54% vs 0%) |
| • | Myalgia (44% vs 31%) |
| • | Nonspecific musculoskeletal pain (35% vs 15%) |
| • | Anxiety/nervousness/tremor (21% vs 9%) |
| • | Dizziness (83% vs 70%) |
| • | Headache (83% vs 33%) |
| • | Hypesthesia/hyperesthesia/paresthesia (12% vs 2%) |
Thrombocytopenia has been reported during uncontrolled clinical trials in patients receiving epoprostenol.
Potential adverse events from postmarketing evaluations include anemia, hypersplenism, pancytopenia, splenomegaly, and hyperthyroidism.
Although the relationship to epoprostenol administration has not been established, pulmonary embolism has been reported in several patients taking epoprostenol and there have been reports of hepatic failure.
References: 1. VELETRI® (epoprostenol) for Injection Full Prescribing Information. Actelion Pharmaceuticals US, Inc. 2. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334:296-301.