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Ramipril prior to thrombolysis attenuates the early increase of PAI-1 in patients with acute myocardial infarction.

Abstract
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.
AuthorsAndreas Wagner, Harald Herkner, Wolfgang Schreiber, Andreas Bur, Christian Woisetschläger, Günther Stix, Anton N Laggner, Michael M Hirschl
JournalThrombosis and haemostasis (Thromb Haemost) Vol. 88 Issue 2 Pg. 180-5 (Aug 2002) ISSN: 0340-6245 [Print] Germany
PMID12195686 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
Chemical References
  • Plasminogen Activator Inhibitor 1
  • Ramipril
Topics
  • Adult
  • Aged
  • Cause of Death
  • Double-Blind Method
  • Drug Therapy, Combination
  • Emergency Medical Services (methods)
  • Female
  • Hemodynamics (drug effects)
  • Humans
  • Hypotension (chemically induced)
  • Ischemia (etiology)
  • Middle Aged
  • Myocardial Infarction (blood, complications, drug therapy)
  • Plasminogen Activator Inhibitor 1 (blood)
  • Ramipril (administration & dosage, pharmacology)
  • Thrombolytic Therapy

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