Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease.
Pulmonary Hypertension is a serious complication of sickle cell disease (SCD), with high morbidity and mortality. Endothelin (ET)-1, a potent vasoconstrictor elevated in SCD, acts through the ET receptors (ETR), ETR-A and ETR-B. Bosentan and ambrisentan are ETR blockers used in primary pulmonary hypertension. We report on the use of ETR blocking agents in a cohort of 14 high-risk SCD adult patients with pulmonary hypertension. Patients underwent right heart catheterization, 6-min walk test, echocardiogram, physical examination and blood work-up before starting ETR blockers. Eight patients received ETR blockers as initial therapy; six patients were already taking sildenafil. Over more than 6 months of therapy, sequential measurements of 6-min walk distance increased significantly (baseline 357 +/- 22 to 398 +/- 18 m at 5-6 months, P < 0.05). Downward trends were observed for amino-terminal brain natriuretic peptide and tricuspid regurgitant velocity. Pulmonary artery mean pressures decreased in three patients that had repeat right heart catheterization (44-38 mmHg). Adverse events were: increased serum alanine aminotransferase (2), peripheral oedema (4), rash (1), headache (3), decreased haemoglobin (2). Therapy was stopped in two patients who were switched then to the other ETR blocker agent. These data suggest preliminary evidence for the benefit of bosentan and ambrisentan in pulmonary hypertension in SCD.
Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Caterina P
CP
Minniti
Roberto F
RF
Machado
Wynona A
WA
Coles
Vandana
V
Sachdev
Mark T
MT
Gladwin
Gregory J
GJ
Kato
D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D006328:Cardiac Catheterization; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D005080:Exercise Test / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D010666:Phenylpropionates / Q000009:adverse effects / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D010879:Piperazines; D011687:Purines; D011724:Pyridazines; D013449:Sulfonamides; D013450:Sulfones; D000068677:Sildenafil Citrate; C467894:ambrisentan; D000077300:Bosentan