Published online Apr 15, 2020. doi: 10.4239/wjd.v11.i4.137
Peer-review started: October 15, 2019
First decision: November 19, 2019
Revised: January 19, 2020
Accepted: February 17, 2020
Article in press: February 17, 2020
Published online: April 15, 2020
Processing time: 174 Days and 0.2 Hours
Clopidogrel remains the most widely prescribed P2Y12 receptor antagonist and is recommended by the latest guidelines for the management of ischemic stroke and acute coronary syndromes. Studies have shown that patients with diabetes mellitus (DM) exhibit a poorer response to clopidogrel than patients without DM, leading to a significant difference in the incidence of recurrence of cardiovascular events and mortality associated with DM. However, the long-term effects of clopidogrel in patients with and without DM have not been systematically reviewed.
We hypothesized that the presence of DM modifies the long-term efficacy of clopidogrel for a reduction in cardiovascular risk. To our knowledge, this is the first meta-analysis to evaluate the efficacy of long-term clopidogrel treatment in patients with ischemic cardiovascular disease, according to the presence or absence of DM.
This study aimed to systematically evaluate the efficacy of clopidogrel for the treatment of acute coronary syndromes or ischemic stroke in patients with or without DM.
A systematic review and meta-analysis of randomized controlled trials.
Six randomized controlled trials, comprising 43,352 participants (13,491 with and 29,861 without DM) who had received antiplatelet therapy for ≥ 3 mo, were included in the meta-analysis. Compared with aspirin alone, a combination of clopidogrel and aspirin significantly reduced the risk of any cardiovascular event in patients without DM (HR = 0.78, 95%CI: 0.71–0.86, P < 0.001; I2 = 23%, P = 0.26). Clopidogrel plus aspirin also significantly reduced cardiovascular risk in patients with DM, although the effect was smaller (HR = 0.89, 95%CI: 0.81–0.99, P = 0.030; I2 = 0%, P = 0.74). Nevertheless, there was no significant difference in the efficacy of clopidogrel at reducing the risk of cardiovascular events in patients with DM vs those without (P for interaction = 0.062).
The present study found that the addition of clopidogrel to aspirin significantly reduced cardiovascular risk in patients with and without DM who had experienced ischemic cardiovascular disease. The beneficial effect of the addition of clopidogrel to aspirin for patients with DM was lower than that in patients without DM, although the modifying effect of DM did not reach significance. In the present study, a weaker effect of clopidogrel was identified in patients with DM, which implies that a new antiplatelet agent is needed for ischemic stroke patients with DM. We hypothesized that the presence of DM modifies the long-term efficacy of clopidogrel for a reduction in cardiovascular risk. Cardiologist and neurologist should pay attention to the presence of DM when provide clopidogrel for patients with ischemic cardiovascular disease.
A systematic review and meta-analysis of randomized controlled trials to summarize the evidence on this topic is important. A new antiplatelet agent is needed for ischemic stroke patients with DM.