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Abstract

To study the safety and efficacy of the thrombolytic agent saruplase as a bolus, the angiographic and clinical outcomes of three bolus regimens were investigated in a pilot study conducted in 192 patients with an acute myocardial infarction and were compared with the standard regimen. Fifty-two patients received a double bolus of 40 mg and 40 mg after 30 minutes, 51 patients a bolus of 80 mg, and 36 patients a bolus of 60 mg. Fifty-three patients received the standard regimen (a bolus of 20 mg and 60 mg IV infusion over 1 hour). At 60 minutes TIMI 2 and 3 flow were, respectively, 9.6% and 61.5% with the 40/40-mg bolus, 15.7% and 51.0% with the 80-mg bolus, 16.7% and 30.6% with the 60-mg bolus, and 7.5% and 54.7% with the standard 20/60-mg infusion. At 90 minutes TIMI 2 and 3 flow improved to 9.6% and 73.1%, 15.7% and 56.9%, 13.9% and 36.1%, and 5.7% and 71.7%, respectively. The primary endpoint, persistent patency (TIMI 2 + 3) at 24-45 hours, was seen in 69.2%, 64.7%, 44.4%, and 67.9% of patients who had no rescue PTCA, respectively. Inclusion in the 60-mg bolus group was prematurely stopped because of their low patency rates. The 40/40-mg bolus group had the highest mortality rate (13.5%), whereas the 60-mg bolus group had no deaths. Other adverse event rates were similar in the four groups. This clinical outcome is highly influenced by rescue PTCA of patients with insufficient TIMI flow. This pilot study indicates that in patients with an acute myocardial infarction, a double bolus of 40/40 mg resulted in the highest patency but also had the highest complication rate. The 80-mg single bolus is an attractive alternative for further evaluation because of its acceptable patency and event profile, and its easy form of administration.

Meta-analysis of randomized phase II trials to inform subsequent phase III decisions

“…[13] 19977 daysICH971020 (0)1 (1.0)Reinfarction4 (4.1)7 (6.9)Vanderschueren et al . [14] 1997Hospital stayICH50520 (0)0 (0)Reinfarction5 (10.0)7 (13.4)BASE [15] 1998Hospital stayICH139532 (1.4)0 (0)Reinfarction9 (6.5)1 (1.9)DOUBLE [16] 199830 daysICH2242372 (0.9)1 (0.4)Reinfarction5 (2.2)12 (5.1)lnTIME [17] 199830 daysICH4781240 (0)1 (0.8)Reinfarction9 (1.9)8 (6.5)TIMI 10B [18] 199830 daysICH5403169 (1.7)6 (1.9)Reinfarction28 (5.2)18 (5.7)TIMIKO [19] 199830 daysICH3502681 (0.3)3 (1.1)Reinfarction11 (3.1)9 (3.4) Phase III trials INJECT [22] 199535 daysICH...…”