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Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting
Deepak L Bhatt1, Michel E Bertrand, Peter B Berger
1Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Insights
Clopidogrel is at least as effective as ticlopidine in preventing major adverse cardiac events (MACE) after coronary stent placement. This meta-analysis indicates clopidogrel should replace ticlopidine as the standard antiplatelet therapy.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Clopidogrel demonstrates improved safety and tolerability over ticlopidine post-coronary stent deployment.
- Previous trials lacked the power to definitively compare the efficacy of clopidogrel versus ticlopidine in reducing ischemic events.
Purpose of the Study:
- To determine if clopidogrel is non-inferior in efficacy to ticlopidine for preventing ischemic events.
- To compare the rates of major adverse cardiac events (MACE) between clopidogrel and ticlopidine in patients receiving coronary stents.
Main Methods:
- A meta-analysis was performed on published data from trials and registries comparing clopidogrel and ticlopidine in patients with coronary stents.
- The primary endpoint was the rate of 30-day major adverse cardiac events (MACE).
Main Results:
- The study included 13,955 patients. Pooled MACE rates were 2.10% for clopidogrel and 4.04% for ticlopidine.
- Clopidogrel showed a significantly lower odds ratio for ischemic events (OR 0.72; 95% CI 0.59-0.89; p=0.002).
- Mortality was also significantly reduced with clopidogrel (OR 0.55; 95% CI 0.37-0.82; p=0.003).
Conclusions:
- Clopidogrel is at least as efficacious as ticlopidine in reducing MACE, with better tolerability and fewer side effects.
- The superior efficacy may be linked to clopidogrel's rapid antiplatelet onset or improved patient compliance.
- Clopidogrel plus aspirin is recommended as the standard antiplatelet regimen post-stent deployment, replacing ticlopidine plus aspirin.
Objectives:
We sought to determine whether clopidogrel is at least as efficacious as ticlopidine.
Background:
Several trials have supported the enhanced safety and tolerability of clopidogrel compared with ticlopidine after coronary stent deployment. However, none of these individual trials were powered to detect possible differences in the efficacy for reducing ischemic end points.
Methods:
Published data from trials and registries that compared clopidogrel with ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed. The rate of 30-day major adverse cardiac events (MACE), as defined in each trial, was used as the primary end point.
Results:
There were a total of 13,955 patients. The pooled rate of major adverse cardiac events was 2.10% in the clopidogrel group and 4.04% in the ticlopidine group. After adjustment for heterogeneity in the trials, the odds ratio (OR) of having an ischemic event with clopidogrel, as compared with ticlopidine, was 0.72 (95% confidence interval [CI] 0.59 to 0.89, p = 0.002). Mortality was also lower in the clopidogrel group compared with the ticlopidine group-0.48% versus 1.09% (OR 0.55, 95% CI 0.37 to 0.82; p = 0.003).
Conclusions:
Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment.