# Efficacy and safety of clopidogrel and aspirin in patients with chronic coronary syndrome: a systematic review and meta-analysis

## TL;DR

This study compares clopidogrel and aspirin for chronic coronary syndrome, finding similar safety and possible modest benefits with combination therapy.

## Contribution

A systematic review and meta-analysis comparing clopidogrel, aspirin, and their combination in chronic coronary syndrome patients.

## Key findings

- Clopidogrel monotherapy showed a lower, but not statistically significant, risk of myocardial infarction compared to aspirin.
- Combination therapy improved treatment response and reduced angina frequency, but with high heterogeneity and subjective outcomes.
- No significant difference in serious bleeding events was found between clopidogrel and aspirin.

## Abstract

To systematically evaluate and compare the efficacy and safety of clopidogrel and aspirin, as well as their combination, in patients with chronic coronary syndrome (CCS), and to provide evidence-based support for long-term antiplatelet therapy in stable coronary artery disease.

A comprehensive literature search was conducted in CNKI, WanFang, PubMed, Web of Science, and Embase databases from January 1990 to July 2025. Randomized controlled trials comparing clopidogrel and aspirin as monotherapy or in combination in patients with CCS were included. Relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models according to heterogeneity. Publication bias and sensitivity analyses were performed where appropriate.

A total of 24 studies involving patients with chronic coronary syndrome were included. Compared with aspirin monotherapy, clopidogrel monotherapy was associated with a numerically lower incidence of myocardial infarction, although the difference was not statistically significant. No significant difference in the risk of serious bleeding events was observed between clopidogrel and aspirin. Combination therapy with clopidogrel and aspirin was associated with a higher treatment response rate and a tendency toward reduced angina frequency compared with aspirin alone; however, substantial heterogeneity was present, and the observed benefits were mainly confined to subjective or semi-quantitative outcomes. The incidence of common adverse reactions, including gastrointestinal discomfort, dizziness, and headache, was numerically lower in the combination therapy group, but these differences did not reach statistical significance.

In patients with chronic coronary syndrome, clopidogrel represents a reasonable alternative to aspirin for long-term antiplatelet therapy, with comparable efficacy and safety. Combination therapy with clopidogrel and aspirin may offer modest improvements in symptom-related outcomes; however, these findings should be interpreted cautiously due to heterogeneity, potential publication bias, and the subjective nature of some endpoints. Individualized antiplatelet strategies based on ischemic and bleeding risk remain essential in stable coronary artery disease.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251108327.