A new thrombolytic agent, monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial.
BACKGROUND
Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered.


METHODS
This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured.


RESULTS
Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 +/- 4 vs 20 +/- 2 ng/mL, P <.01) and in Group II (36 +/- 3 vs 27 +/- 2 ng/mL, P <.05). In the high PAI-1 level subgroup (> or =27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P <.01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald chi2= 3.94, P =.02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II.


CONCLUSIONS
Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI.
D015906:Angioplasty, Balloon, Coronary; D000990:Antithrombin III; D003131:Combined Modality Therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000628:therapy*; D010447:Peptide Hydrolases / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011446:Prospective Studies; D012044:Regression Analysis; D014654:Vascular Patency
D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; C046193:antithrombin III-protease complex; C468277:monteplase; D000990:Antithrombin III; D010447:Peptide Hydrolases; D010960:Plasminogen Activators