Patients undergoing coronary stenting are almost always treated with two antiplatelet agents, such as aspirin and a thienopyridine. The latter has traditionally been ticlopidine, but for a number of years a safer analogue of ticlopidine -- clopidogrel -- has been adopted in many countries. However, no definitive data on the comparative efficacies of ticlopidine versus clopidogrel have been available to date.

Now, an analysis of seven pertinent trials using a total of 3,382 patients, with an average follow-up of 7 months has definitely shown that clopidogrel is superior to ticlopidine -- whenever the former is given with an initial loading dose. In five of the studies both clopidogrel and ticlopidine were started with a loading dose; in one trial clopidogrel was administered without loading, and in another clopidogrel could be administered with or without loading.

The overall comparison of odds ratios for death or nonfatal MI revealed similar results for clopidogrel and ticlopidine (OR=1.11, P =.57). But when the investigators compared studies administering clopidogrel with a loading dose versus those using ticlopidine, they found that odds ratios were significantly better in favour of clopidogrel (OR =.59, P =.04) regarding the primary outcomes of death or nonfatal MI.

"Our meta-analysis is the first to show that, as long as clopidogrel is given with a loading dose, this agent is superior to ticlopidine," said Dr. Zoccai. "Given these findings, a loading dose of clopidogrel plus aspirin should be considered the standard treatment for patients undergoing coronary stenting," Dr. Biondi Zoccai suggested.

In a related study, the same group of researchers performed a systematic review and meta-analysis of clinical trials to identify the optimal clopidogrel loading dose regimen in this setting. The analysis included five randomised trials and two controlled studies, for a total of 1,535 patients (685 treated with a 300 mg loading dose, 767 with a 600 mg, 54 with 900 mg, and the remaining 29 with other regimens).

Overall, a high loading dose of at least 600 mg proved significantly superior to a standard loading (300 mg) in preventing inhospital MI (OR =.51, P =.05), as well as death or nonfatal MI at 30 days (OR =.53, P =.02).

Sensitivity analyses restricted to randomised trials further confirmed the superiority of high loading dose, with even more statistically significant reductions in the rate of inhospital and one-month events (P =.02 and P =.005, respectively). There was no statistically significant increase in major or minor bleeding (P =.55 and P =.98, respectively) in patients receiving the 600 mg versus those treated with the 300 mg loading dose.

"These findings clearly and significantly support the use of a high loading dose in patients undergoing coronary stenting. A 600 mg clopidogrel loading dose should be routinely used in such patients, unless the bleeding risks clearly offset the expected benefits," Dr. Biondi Zoccai concluded.


[Presentation titles: Benefits of Clopidogrel in Patients Undergoing Coronary Stenting Significantly Depend on Loading Dose: Evidence From a Meta-Regression. Abstracts D-40. Superiority of a High Clopidogrel Loading Dose Regimen in Patients Undergoing Percutaneous Coronary Intervention: Evidence From a Meta-Analysis. Abstracts D42]

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