Conference: 2009 PH Resource Network Symposium
Release Date: 09.24.2009
Presentation Type: Abstracts
Aaron B. Waxman, MD, PhD; Laurie Lawler, RN
Massachusetts General Hospital, Boston, MA
BACKGROUND: Cicletanine is a racemic furopyridine that has both vasorelaxant and diuretic proprieties, and has been a safe and effective drug for treatment of hypertension in Europe. Several preclinical studies have suggested that cicletanine relaxes vascular smooth muscle, in part, through an endothelium-dependent action mediated by cyclooxygenase and eNOS coupling, with resultant increases in nitric oxide production, and decreases in peroxynitrite or O2 production.
METHODOLOGY: We have evaluated the tolerability of cicletanine 200mg-daily in patients with PAH on a compassionate use basis. A total of 9 patients were included, 1 NYHA functional class 4, 5 functional class 3, and 2 functional class 2. All patients were on at least one approved oral PAH therapy, and 7 patients were on a prostanoid. Four of the 9 patients were on a PDE5 inhibitor as part of their background therapy. We evaluated patients after 3-months treatment. Tolerability was based on vital signs and side effects, renal function (BUN/Creatinine), hemoglobin, and electrolytes.
FINDINGS: All patients reported subjective improvement in dyspnea and functional class, improving at least 1 NYHA class. There were no occurrences of hypotension. In all cases, heart rates either decreased or remained stable. Two patients had asymptomatic hypokalemia, and diuretics were adjusted with resolution. While all patients experienced weight loss, there were no significant changes in BUN/Creatinine, or hemoglobin.
IMPLICATIONS: Cicletanine could represent a new, important class of drugs to treat pulmonary hypertension. Further study of this agent in PAH is warranted.