Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction

Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is co mmonly 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 o ther thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activatin g factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n = 35), or matching placebo (n = 36), was administered intravenou sly over 5 min, in a randomized double-blinded protocol, to consecutive pat ients about to receive SK for AMI; all but three had inferior MI, because o f the preference for strategies other than SK therapy in patients with ante rior Mi. The rate of infusion of SK was set to give 1.5 x 10(6) units over 30 min, anticipating significant hypotension. Blood pressure fell sharply o ver the first 10 min of SK administration. The maximum fall in systolic blo od pressure occurred between 8 and 12 min, and averaged 43 +/- 28 mm Hg (me an +/- S.D.) and 40 +/- 26 mmHg in patients given placebo and lexipafant re spectively. Systolic pressure having fallen to < 90 mmHg, according to prot ocol the SK administration rate was reduced in 21 of 36 (58%) of patients g iven 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 adv erse effects attributable to lexipafant. It is concluded that the PAF recep tor antagonist lexipafant has no significant effect on SK-induced hypotensi on and does not facilitate an accelerated regimen of administration.