Side effects of prostacyclin in patients with angina pectoris and coronary artery disease

Although the exposure of human subjects to prostacyclin (PGI2) infusion has been broad, no systematic approaches have been made in order to investigate the dose-related side effects in patients with angina pectoris and coronary artery disease (CAD). We studied 25 patients with typical chest pain and overt CAD. All patients underwent a cycloergometer stress testing (25 W increments at 2-min intervals). PGI2 was infused in scalar doses up to 10 ng/kg/min. During the infusion 25 patients (100%) had facial flushing, 7 (28%) moderate headache and one (4%) had nausea. In addition, 4 patients experienced the typical chest pain and had significant (≥0.1 mV) ST segment depression at 8·10 ng/kg/min infusion rates. These patients had lower tolerance to exercise (67.7±1.7vs. 8.8±1.9 min; p<0.05) and coronary artery lesions more severe than those observed in patients without drug-induced angina pectoris. Our data therefore indicate that PGI2 at therapeutic doses may induce myocardial ischemia in patients with angina pectoris, low tolerance to exercise and severe CAD. In patients with mild to moderate degree of CAD, PGI2 was found to be well tolerated. These findings suggest that patients with angina pectoris and low tolerance to exercise should be excluded from clinical studies directed at elucidating the effectiveness of PGI2 in cardiovascular disorders.