[Antiaggregant effect and tolerance of calcium carbasalate administrated immediately after aorto-coronary bypass. Results of a double-blind versus placebo study].
The patency of aorto-coronary bypasses is greatly influenced by platelet aggregability, and there is an associated risk of thrombosis which may occur very early during surgery. It is in this context that aspirin has been the subject of successful clinical studies. When administering aspirin, it is preferable to choose formulations that are well tolerated by the gastro-intestinal tract. This was the reason for carrying out the present randomised single-centre double-blind parallel-group study aimed at confirming the platelet anti-aggregant effect and tolerability of calcium carbasalate administered during the immediate postoperative period. The dose prescribed was equivalent to aspirin 325 mg daily, and was given as a single dose 6 hours after the end of the operation and repeated for 7 days, versus placebo, in 56 patients undergoing aorto-coronary bypass grafts. A clinical assessment, ECG, platelet count and measurements of CPK and CPK-MB were carried out daily for the 7 days of the study. Tests of platelet aggregation (to arachidonic acid, ADP and collagen), assays of serum thromboxane B2, MDA and PDF, and urinary assays for beta-thromboglobulin and 6-keto-PGF-1 were carried out before treatment, then 1 and 7 days after the start of treatment. Fifty males (89%) and 6 females, mean age 58.3 years, received treatment with either calcium carbasalate (group C, n = 28) or placebo (group P, n = 28). The atheromatous lesions present in most cases represented triple-vessel disease (37 cases), and most operations were triple bypasses (23 cases) or double bypasses (20 cases). A significant reduction in platelet aggregation to arachidonic acid and collagen on D1 (p = 0.05) and D7 (p < 0.001), and to ADP on D7 (p < 0.01) was observed in group C as compared with group P. Group C also showed significant reductions as compared with group P in respect of serum thromboxane B2 levels on D1 (p < 0.01) and D7 (p < 0.001) and MDA levels on D1 and D7 (p < 0.001). No significant difference was demonstrated between the two groups in respect of urinary 6-keto-PFG-1 excretion. The number of patients showing a rise in CPK was lower in group C but this difference did not reach statistical significance. ST segments change were comparable in the two groups, and no patient complained of anginal pain during the study. These results show that calcium carbasalate administered at a dose equivalent to 325 mg aspirin daily caused very early inhibition of platelet aggregation, specifically inhibiting platelet production of thromboxane B2 without altering prostacyclin levels. In addition, calcium carbasalate was found to be well tolerated. This study confirms the value of early administration of aspirin at a dose of 325 mg daily during the hours immediately following aorto-coronary bypass graft surgery.
Mathieu
P
P
Services de Chirurgie Cardiaque, CHU Brabois, Vandoeuvre-Les-Nancy, France.
Villemot
J P
JP
Stoltz
J F
JF
Scheck
F
F
Garnier
L F
LF
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000368:Aged; D000700:Analgesics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis; D001241:Aspirin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D011182:Postoperative Care; D013929:Thromboxane B2 / Q000097:blood; D014508:Urea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001620:beta-Thromboglobulin / Q000652:urine
D000700:Analgesics; D005338:Fibrin Fibrinogen Degradation Products; D001620:beta-Thromboglobulin; D008315:Malondialdehyde; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D014508:Urea; D000990:Antithrombin III; C002942:carbaspirin calcium; D001241:Aspirin
Efficacité Antiagrégante et tolérance du carbasalate calcique administré dans les suites immédiates des pontages aorto-coronaires. Résultats d'une étude réalisée en double aveugle versus placebo.