Drug-testing in patients with pulmonary hypertension of unknown cause

The acute haemodynamic effects of seven different drugs were serially evaluated in eight patients suffering from pulmonary hypertension of unknown cause. The following drugs were tested in randomized order: nifedipine, amrinone, isoproterenol, captopril, prostacyclin, dihydralazine and nitroglycerin. Only a reduction in pulmonary vascular resistance (PVR) of more than 30% of baseline was considered a satisfactory response. Overall, the decrease in PVR ranged from 9 +/- 12% (nitroglycerin) to 38 +/- 23% (prostacyclin). However, marked inter- and intra-individual variability in the efficacy of all drugs was observed, making cross reactivity totally unpredictable. The number of responders for each drug varied between five (prostacyclin) and zero (dihydralazine, nitroglycerin). Conversely, a maximum of three drugs was capable of eliciting a response in an individual patient, with only two out of eight patients being total non-responders. A reduction in PVR of more than 30% (n = 16) was associated with a significant decrease in mean pulmonary artery pressure (49.1 +/- 8.2 versus 39.4 +/- 6.4 mmHg) and a significant increase in cardiac index (2.5 +/- 0.6 versus 3.4 +/- 0.8l.min-1.m-2). Overall, none of the drugs tested proved to be clearly superior. However, because of marked inter- and intra-individual variability, the therapeutic approach must be based on trial and error and the evaluation of all drugs is indicated if one fails.