Ramipril prior to thrombolysis attenuates the early increase of PAI-1 in patients with acute myocardial infarction.
In a placebo-controlled, double-blinded, randomized study we evaluated the effect of ramipril prior to thrombolysis on the course of PAI-1 plasma levels and on the frequency of postinfarct ischemic events in patients with acute myocardial infarction. Fifty-one out of 99 patients received 2.5 mg ramipril orally prior to thrombolysis and 12 h later. The blood samples for determination of PAI-1 plasma levels were collected on admission and 2, 4, 8, 12 and 24 h after thrombolysis. Postinfarct ischemic events were registered until coronary angiography was performed and defined as recurrent chest pain and/or evidence of ischemic signs on the ECG (ST-depression or ST-segment elevation of 1 mm in one or more inferior or anterior leads). Coronary angiography was performed within 7 days after the onset of myocardial infarction. Patients were classified into two groups: those without reperfusion of the infarct-related artery (TIMI grade 0 or 1) and those with reperfusion of the infarct-related artery (TIMI grade 2.3). On admission, PAI-1 plasma levels were similar in both groups (ramipril: 47.1 [4.8] ng/ml; placebo: 49.1 [4.8] ng/ml). The PAI-1AUC was 77.2 [6.7] ng/ml/h in the ramipril group and 95.4 [6.2] ng/ml/h in the placebo group (p = 0.013). Significant differences between groups were observed at 4, 8 and 12 h after thrombolysis (4 h: 85.5 (11.3) vs. 116 (12.3) ng/ml, p < 0.01; 8 h: 79.1 (11.2) vs. 100.9 (9.3) ng/ml, p < 0.01; 12 hrs: 71.3 (9.5) vs. 87.4 (7.7) ng/ml, p < 0.05). The relative frequency of postinfarct ischemic events was significantly lower in the ramipril group (2.5% versus 7.1%, p = 0.001). Additionally, we observed a significant higher rate of TIMI grade 2 and 3 of the infarct-related artery in patients receiving oral ramipril compared to the placebo group (73% versus 54%; p = 0.035). Our study demonstrates a favorable effect of ramipril on the fibrinolytic system after thrombolysis associated with a lower rate of postinfarct ischemic events within the first days after myocardial infarction. Therefore, the application of ramipril prior to thrombolysis appears to be a reasonable concomitant treatment which may reduce early infarct-related complications.
Wagner
Andreas
A
Department of Emergency Medicine, General Hospital, University of Vienna, Austria.
Herkner
Harald
H
Schreiber
Wolfgang
W
Bur
Andreas
A
Woisetschläger
Christian
C
Stix
Günther
G
Laggner
Anton N
AN
Hirschl
Michael M
MM
D000328:Adult; D000368:Aged; D002423:Cause of Death; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004632:Emergency Medical Services / Q000379:methods; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007511:Ischemia / Q000209:etiology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D017257:Ramipril / Q000008:administration & dosage* / Q000494:pharmacology; D015912:Thrombolytic Therapy
D017395:Plasminogen Activator Inhibitor 1; D017257:Ramipril