Safety and efficacy evaluation of clopidogrel compared to ticlopidine after stent implantation: an updated meta-analysis

Abstract

Background: Combination therapy with aspirin plus ticlopidine has become the reference antithrombotic therapy after coronary stenting. However despite its effectiveness, ticlopidine is associated with a significant incidence of severe side effects. Thus, clopidogrel, a ticlopidine analogue with an excellent safety profile, has been introduced in clinical practice. To date only a few, underpowered studies comparing the clinical efficacy of clopidogrel and aspirin versus standard combination therapy after coronary stenting have been performed and the odds ratios (OR) vary substantially among them. The purpose of the present investigation was to update the data regarding this issue by means of a formal meta-analysis.

Methods: Ten studies were considered suitable for analysis. The OR were calculated for 30 days of follow-up in patients who had undergone successful coronary stenting. Primary endpoints were a composite of death and non-fatal myocardial infarction (MI) (efficacy endpoint) as well as a composite of major adverse side effects (safety endpoint) as considered in every single study. Secondary endpoints were a composite of major adverse cardiac events, according to single study definition, and individual cardiac events as well.

Results: Overall, 11688 patients were included. At 30 days, the OR for death and non-fatal MI was 0.63 (95% confidence interval-CI 0.47 to 0.85, p = 0.003) in favor of patients treated with clopidogrel and aspirin. There was also a trend toward less major adverse cardiac events (OR 0.83, 95% CI 0.66 to 1.03, p = 0.1), less mortality (OR 0.70, 95% CI 0.40 to 1.25, p = 0.2), and less non-fatal MI (OR 0.76, 95% CI 0.54 to 1.07, p = 0.1). Furthermore, OR for major adverse side effects was 0.53 (95% CI 0.42 to 0.66, p < 0.00001) in favor of clopidogrel. Similarly, drug intolerance was significantly reduced by clopidogrel (OR 0.51, 95% CI 0.36 to 0.72, p < 0.0001). Fewer patients on clopidogrel developed neutropenia or thrombocytopenia (OR 0.58, 95% CI 0.18 to 1.81, p = 0.3), while the incidence of severe bleeding was similar in the two groups (OR 1.19, 95% CI 0.71 to 1.99, p = 0.5).

Conclusions: The present meta-analysis demonstrates that clopidogrel reduces the 30-day combined endpoint of death and non-fatal MI, thereby showing a superior clinical efficacy compared to ticlopidine in patients who had undergone successful coronary stenting. A significantly better safety profile than ticlopidine was also reported, confirming on a larger scale the findings of randomized comparative trials.