Ridogrel as an adjunct to thrombolysis in acute myocardial infarction.
An open pilot study was performed to assess the safety and preliminary efficacy of ridogrel, a selective thromboxane-A2 synthetase inhibitor and thromboxane-A2/prostaglandin endoperoxide receptor blocker, as adjunct to thrombolysis, with alteplase and heparin. In 50 patients with acute myocardial infarction, 300 mg ridogrel was injected intravenously in addition to alteplase and heparin. Ridogrel was continued orally (300 mg) twice daily for 5 days. Patency rate at initial (90 min) angiography, defined as thrombolysis in myocardial infarction perfusion grades 2 or 3, was 86%. Rescue percutaneous transluminal coronary angioplasty was performed in 10 patients; immediate results were good in nine, while a large dissection occurred in one patient. New ischemia occurred in 10 patients within 24 h, and after the second angiogram in seven cases. Three underwent coronary artery bypass grafting and seven percutaneous transluminal coronary angioplasty without further complication. Patency rate at second angiography (between 6 and 24 h) was 94%. New Q-waves appeared in 56% of the patients; 36% had a non-Q-wave infarction and 8% had no enzyme rise. Enzymatic infarct size, estimated by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase released in 72 h, was substantially smaller than in comparable studies with rt-PA and heparin. One patient died due to a cerebrovascular hemorrhage. No other deaths occurred. Bleeding complications were seen in 18 patients (36%), necessitating blood transfusion in three. Reinfarction did not occur. Eventually 49 patients were discharged in good condition. Safety with regard to bleeding complications of ridogrel in conjunction with alteplase is about the same as that of aspirin. Immediate and late patency rates were high. Rescue percutaneous transluminal coronary angioplasty could be performed with relative safety and early reocclusion could be successfully dealt with by repeat percutaneous transluminal coronary angioplasty. Further studies with this or similar compounds seem warranted.
van der Wieken
L R
LR
Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands.
Simoons
M L
ML
Laarman
G J
GJ
Van den Brand
M
M
Nijssen
K M
KM
Dellborg
M
M
Hermens
W
W
Vrolik
W
W
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D017023:Coronary Angiography / Q000009:adverse effects; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000628:therapy; D010421:Pentanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D010960:Plasminogen Activators / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012008:Recurrence; D015912:Thrombolytic Therapy; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014654:Vascular Patency
D005343:Fibrinolytic Agents; D010421:Pentanoic Acids; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D017482:Receptors, Thromboxane; D006493:Heparin; C035749:2-hydroxybutyrate dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D013930:Thromboxane-A Synthase; C060219:ridogrel