Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group.
Current limitations of recombinant tissue-type plasminogen activator (rt-PA) therapy for acute myocardial infarction include failure to achieve recanalization in 25% of patients, reocclusion and reperfusion injury. Iloprost, a stable analogue of prostacyclin (PGI2), has been demonstrated to facilitate thrombolysis and reduce myocardial stunning in experimental models. To evaluate combined therapy, rt-PA (100 mg 3 h) and Iloprost (2 ng/kg per min for 48 h) were administered to 25 patients and then rt-PA alone (same dose) was given to an additional 25 patients with evolving myocardial infarction. At 90 min after drug administration, infarct-related vessel patency was observed in 11 (44%) of 25 who received rt-PA plus Iloprost compared with 15 (60%) of 25 who received rt-PA alone (p = 0.26). At 1 week, reocclusion had occurred in 3 (14%) of 21 patients who received combined therapy compared with 6 (26%) of 23 patients treated with rt-PA alone (p = 0.46). Ejection fraction increased significantly from baseline to 7 days for rt-PA alone whereas it decreased with combined therapy (rt-PA alone whereas it decreased with combined therapy (rt-PA alone: 47.3 +/- 11.5% at baseline to 50.4 +/- 9.8% at 7 days; rt-PA plus Iloprost: 51.3 +/- 10.1% at baseline to 49.0 +/- 9.4% at 7 days; difference between groups p = 0.05). At 4 h after therapy, fibrinogen decreased 33% for rt-PA plus Iloprost compared with a 52% for rt-PA alone (p = 0.001). Fibrinogen degradation products increased 60% more for rt-PA alone than for rt-PA plus Ilprost. Thus, the combination of rt-PA plus Iloprost at the doses employed did not improve immediate or follow-up coronary artery patency or left ventricular functional recovery compared with that achieved with rt-PA alone.
Topol
E J
EJ
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Ellis
S G
SG
Califf
R M
RM
George
B S
BS
Stump
D C
DC
Bates
E R
ER
Nabel
E G
EG
Walton
J A
JA
Candela
R J
RJ
Lee
K L
KL
D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016285:Iloprost; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D013318:Stroke Volume / Q000187:drug effects; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
D002317:Cardiovascular Agents; D011994:Recombinant Proteins; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D016285:Iloprost