Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension.
In a subset of patients with primary pulmonary hypertension (PPH), high doses of oral calcium-channel blockers (CCB) produce a sustained clinical and haemodynamic improvement. However, significant side-effects have been reported during acute testing with CCB. Therefore, to identify accurately patients who may benefit from long-term CCB therapy, there is a need for a safe, potent and short-acting vasodilator. The aim of this study was to compare the acute response to inhaled nitric oxide (NO) and oral high doses of CCB in 33 consecutive patients with PPH. A significant acute vasodilator response was defined by a fall in both mean pulmonary artery pressure and total pulmonary resistance by >20%. Ten patients responded acutely to NO, nine of whom responded acutely to CCB, without any complications. The 23 other patients failed to respond to NO and CCB. In these nonresponders, nine serious adverse events were observed with CCB (38%). There was no clinical or baseline haemodynamic feature predicting acute vasodilator response. Long-term oral treatment with CCB was restricted to the nine acute responders and a sustained clinical and haemodynamic improvement was observed in only six patients. In primary pulmonary hypertension, the acute response rate to high doses of calcium-channel blockers is low (27%). Serious adverse reactions to high doses of calcium-channel blockers during acute testing are frequently observed in nonresponders. It is concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who respond acutely to calcium-channel blockers and may benefit from long-term treatment with these agents.
Sitbon
O
O
Service de Pneumologie et Réanimation Respiratoire, UPRES Maladies Vasculaires Pulmonaires, Hôpital Antoine Béclère, Université Paris XI, Clamart, France.
Humbert
M
M
Jagot
J L
JL
Taravella
O
O
Fartoukh
M
M
Parent
F
F
Herve
P
P
Simonneau
G
G
D000280:Administration, Inhalation; D000284:Administration, Oral; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D009569:Nitric Oxide; D004110:Diltiazem; D009543:Nifedipine