Biological efficacy of low versus medium dose aspirin after coronary surgery: results from a randomized trial [NCT00262275].

BACKGROUND: The beneficial effect of aspirin after coronary surgery is established; however, a recent study reported the inability of low doses (100 mg) to inhibit postoperative platelet function. We conducted a double-blind randomised trial to establish the efficacy of low dose aspirin and to compare it against medium dose aspirin. METHODS: Patients undergoing coronary surgery were invited to participate and consenting patients were randomised to 100 mg or 325 mg of aspirin daily for 5 days. Our primary outcome was the difference in platelet aggregation (day 5 - baseline) using 1 microg/ml of collagen. Secondary outcomes were differences in EC50 of collagen, ADP and epinephrine (assessed using the technique of Born). RESULTS: From September 2002 to April 2004, 72 patients were randomised; 3 patients discontinued, leaving 35 and 34 in the low and medium dose aspirin arms respectively. The mean aggregation (using 1.1 microg/ml of collagen) was reduced in both the medium and low dose aspirin arms by 37% and 36% respectively. The baseline adjusted difference (low - medium) was 6% (95% CI -3 to 14; p = 0.19). The directions of the results for the differences in EC50 (low - medium) were consistent for collagen, ADP and epinephrine at -0.07 (-0.53 to 0.40), -0.08 (-0.28 to 0.11) and -4.41 (-10.56 to 1.72) respectively, but none were statistically significant. CONCLUSION: Contrary to recent findings, low dose aspirin is effective and medium dose aspirin did not prove superior for inhibiting platelet aggregation after coronary surgery.

Biological efficacy of low against medium dose aspirin regimen after coronary surgery: analysis of platelet function.

The failure of aspirin to inhibit platelet function has been documented in patients undergoing coronary artery bypass graft (CABG) surgery, but the causes of "aspirin-resistance" remain uncertain. The aim of this study was to investigate the efficacy of aspirin in patients undergoing CABG surgery receiving either 100 mg or 325 mg of oral aspirin for 5-days. Platelet function was tested the day before surgery and on day +1 and day +5, and evaluated by changes in collagen-induced thromboxane-A2 (TxA2) release and platelet aggregation following stimulation with collagen, ADP and epinephrine. In all patients, baseline platelet aggregation was significantly inhibited by pre-incubation with in vitro aspirin (150 micromol/l), with a mean reduction in TxA2-release of >or=95.5% (82.3,99.1). After 5-days of oral aspirin, platelet aggregation was significantly inhibited, and was not further inhibited by in vitro aspirin. Oral aspirin was also associated with a >or=99.5% (97.8, 99.7) reduction in TxA2-release, and with the reversal of the second-phase of ADP-induced aggregation which is TxA2-dependent. In addition a single-dose of 325 mg aspirin on the first post-operative morning may have a greater inhibitory effect on collagen-induced aggregation than 100 mg aspirin. Western blot analysis provided no evidence for the presence of COX-2 in platelets, while the up-regulation of p38-MAPK following platelet-stimulation and surgery was seen. The inhibition of COX-2 (NS398) or p38-MAPK (SB203580) activity did not affect platelet aggregation and TxA2-release on day +5. In summary, there was no evidence for inherent or acquired aspirin-resistance in this surgical population, or for the involvement of either COX-2 or p38-MAPK.

Clopidogrel did not inhibit platelet function early after coronary bypass surgery: A prospective randomized trial.

OBJECTIVE: Although the beneficial effect of aspirin prescription after coronary surgery has been established, the efficacy of clopidogrel has never been compared with that of aspirin in the critical early postoperative period. We therefore conducted a prospective, double-blind, randomized controlled trial to compare the efficacies of these antiplatelet regimens. METHODS: Patients undergoing elective primary coronary artery bypass surgery were invited to participate. After the operation, patients were randomized to receive 100 mg aspirin, 325 mg aspirin, or 75 mg clopidogrel tablets daily for 5 days. Our primary outcome measure was platelet aggregation on day 5, expressed as percentage of baseline. Assessment of platelet aggregation was undertaken with the technique of Born. RESULTS: From September 2002 to July 2003, a total of 54 patients were randomized into the study. There were 2 self-withdrawals and 2 protocol violations, leaving 50 patients for analysis, 34 in the aspirin group and 16 in the clopidogrel arm. Compared with baseline, the mean percentage aggregations with collagen on day 5 were 56% for aspirin and 99% for clopidogrel. The mean difference between the two arms was 42% (95% confidence interval 27%-56%) in favor of aspirin. At the same time point, the effective concentration to inhibit 50% aggregation in the samples from patients randomly assigned to receive clopidogrel were not raised for our entire panel of agonists (changes of -0.04 microg/L for collagen, -0.01 micromol/L for epinephrine, and -0.02 micromol/L for adenosine diphosphate). CONCLUSION: Clopidogrel, unlike aspirin, did not inhibit platelet aggregation in the first 5 postoperative days and therefore should not be used as a sole antiplatelet agent early after coronary surgery.