Hemodynamic, platelet and clinical responses to prostacyclin in unstable angina pectoris.
The hemodynamic and platelet effects of prostacyclin (PGI2) were investigated in 27 patients with unstable angina (14 treated patients; 13 control subjects) given a 72-hour infusion (5 ng/kg/min) or placebo. This randomized study was double-blind and conducted as a substudy of a multicenter trial testing the clinical efficacy of PGI2. The clinical and angiographic features were identical in the 2 groups. Blood pressure and heart rate were not modified significantly by PGI2. A recurrence of angina during infusion occurred in 8 treated patients (57.1%) and in 8 control subjects (61.5%). Two patients receiving PGI2 and none in the control group developed a myocardial infarction. Levels of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, increased from baseline values (less than 20 pg/ml) to 605 +/- 41 pg/ml during infusion. Levels of fibrinopeptide A, beta-thromboglobulin, platelet factor 4, thromboxane B2 and the platelet aggregates ratio in blood were similar between the 2 groups before, during and after PGI2 infusion. Prostacyclin reduced ex vivo platelet aggregation to adenosine diphosphate and thromboxane B2 generation by approximately 50% during the infusion period with return of aggregation to baseline and platelet thromboxane B2 production to above baseline after the discontinuation of PGI2. Thus, despite favorable effects of PGI2 upon platelet aggregation and systemic hemodynamics, the prostanoid failed to improve the clinical evolution of unstable angina.
Théroux
P
P
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Latour
J G
JG
Diodati
J
J
Léger-Gauthier
C
C
Morissette
D
D
Bosch
X
X
de Lara
J
J
Waters
D
D
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects*; D004311:Double-Blind Method; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D005344:Fibrinopeptide A / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D013929:Thromboxane B2 / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D005344:Fibrinopeptide A; D010978:Platelet Factor 4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol