Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2020; 11(4): 137-149
Published online Apr 15, 2020. doi: 10.4239/wjd.v11.i4.137
Long-term effect of clopidogrel in patients with and without diabetes: A systematic review and meta-analysis of randomized controlled trials
Li-Rong Liang, Qian Ma, Lin Feng, Qi Qiu, Wen Zheng, Wu-Xiang Xie
Li-Rong Liang, Department of Clinical Epidemiology & Tobacco Dependence Treatment Research, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Qian Ma, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
Lin Feng, Wu-Xiang Xie, Peking University Clinical Research Institute, Peking University First Hospital, Beijing 100034, China
Qi Qiu, Institute of Clinical Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
Wen Zheng, Emergency Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
Author contributions: Liang LR and Ma Q contributed equally to this work; Xie WX conceived and designed the study; Xie WX carried out the literature searches; Liang LR and Ma Q extracted the data; Feng L and Xie WX assessed the study quality; Liang LR, Ma Q, and Xie WX performed the statistical analysis. Liang LR and Xie WX wrote the manuscript; Ma Q, Feng L, Qiu Q, and Zheng W revised the manuscript.
Supported by the National Natural Science Foundation of China, No. 81974490; Fundamental Research Funds for the Central Universities of China, No. BMU2017YJ005.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA Checklist (2009), and the manuscript was prepared and revised according to the PRISMA Checklist (2009).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wu-Xiang Xie, PhD, Associate Professor, Peking University Clinical Research Institute, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China. xiewuxiang@hsc.pku.edu.cn
Received: October 15, 2019
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
Abstract
BACKGROUND

Previous studies have shown that patients with diabetes mellitus (DM) respond poorly to clopidogrel treatment.

AIM

To systematically evaluate the efficacy of clopidogrel for the treatment of acute coronary syndromes or ischemic stroke in patients with or without DM.

METHODS

PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched from 1980 on 27 June 2019 to identify relevant randomized controlled trials that compared the effect of a combination of clopidogrel and aspirin with aspirin alone. A random-effects meta-analysis was used to estimate the hazard ratio (HR) and its 95% confidence interval (CI). Sensitivity analysis was performed using a fixed-effect model. The I2 statistic was used to evaluate the heterogeneity of the study data.

RESULTS

Six randomized controlled trials, comprising 43352 participants (13491 with and 29861 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).

CONCLUSION

Thus, the present study shows that the addition of clopidogrel to aspirin significantly lowers cardiovascular risk in patients with or without DM who have 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.

Keywords: Clopidogrel; Diabetes; Aspirin; Meta-analysis; Randomized controlled trial

Core tip: The long-term effects of clopidogrel in patients with and without diabetes mellitus (DM) have not been systematically reviewed. The present meta-analysis firstly investigated the modifying effect of DM on the efficacy of long-term clopidogrel treatment in patients with ischemic cardiovascular disease. Although the analysis showed that the hazard ratio reduction in patients with DM was less than that in those without, this difference was not significant. The efficacy of dual antiplatelet therapy with clopidogrel and aspirin appeared to be slightly lower in patients with DM, emphasizing the need for individualized antiplatelet treatment for patients with DM after myocardial infarction or ischemic stroke.