title: Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction.
abstract: Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is commonly limited by the hypotension that is induced. If this could be avoided, an accelerated regimen of SK could be given, analagous to that used for other thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activating factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n=35), or matching placebo (n=36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI. The rate of infusion of SK was set to give 1.5x10(6) units over 30 min, anticipating significant hypotension. Blood pressure fell sharply over the first 10 min of SK administration. The maximum fall in systolic blood pressure occurred between 8 and 12 min, and averaged 43+/-28 mmHg (mean+/-S.D.) and 40+/-26 mmHg in patients given placebo and lexipafant respectively. Systolic pressure having fallen to <90 mmHg, according to protocol the SK administration rate was reduced in 21 of 36 (58%) of patients given placebo and in 19 of 35 (54%) of patients given lexipafant. The total SK dose was given to all subjects over 40.3+/-17.5 and 40.2+/-13.4 min for the placebo and lexipafant groups respectively. Peak and time integrals of creatine kinase were not different in the two groups. There were no adverse effects attributable to lexipafant. It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration.
authors.affiliation: Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia. Helen.Toey@health.wa.gov.au
authors.forename: R
authors.initials: R
authors.lastname: Taylor
authors.forename: D
authors.initials: D
authors.lastname: Fatovich
authors.forename: T
authors.initials: T
authors.lastname: Hitchcock
authors.forename: C
authors.initials: C
authors.lastname: Morrison
authors.forename: L
authors.initials: L
authors.lastname: Curtis
mesh_terms: D000368:Aged; D003402:Creatine Kinase / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use*; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013300:Streptokinase / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000009:adverse effects
chemical_list: D007093:Imidazoles; D010972:Platelet Activating Factor; D003402:Creatine Kinase; D013300:Streptokinase; D007930:Leucine; C103289:lexipafant