Tasoudis PT, Kyriakoulis IG, Sagris D, et al. Clopidogrel Monotherapy versus Aspirin Monotherapy in Patients with Established Cardiovascular Disease: Systematic Review and Meta-Analysis. Thromb Haemost. 2022 May 16. doi: 10.1055/a-1853-2952. (Systematic review)

BACKGROUND: There is no clear consensus on whether aspirin offers better outcomes in terms of secondary cardiovascular disease prevention compared with clopidogrel.

OBJECTIVE: The aim of the study was to compare the safety and efficacy of clopidogrel versus aspirin in patients with established cardiovascular disease.

METHODS: A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases (last search date: August 28, 2021) was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized control trials (RCTs) of clopidogrel versus aspirin as monotherapy in patients with established cardiovascular disease. Random-effects meta-analyses were performed.

RESULTS: Five RCTs incorporating 26,855 patients (clopidogrel: 13,426; aspirin: 13,429) were included. No statistically significant difference was observed between clopidogrel and aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% confidence interval, CI: 0.91-1.13]; p = 0.83), ischemic stroke (OR: 0.87 [95% CI: 0.71-1.06]; p = 0.16), and major bleeding rates (OR: 0.77 [95% CI: 0.56-1.06]; p = 0.11). Patients receiving clopidogrel had borderline lower risk for major adverse cardiovascular events (MACE) (OR: 0.84 [95% CI: 0.71-1.00]; p = 0.05) and lower risk for nonfatal myocardial infarction (OR: 0.83 [95% CI: 0.71-0.97]; p = 0.02, relative risk reduction = 16.9%, absolute risk reduction = 0.5%, number needed to treat = 217 for a mean period of 20 months) compared with patients receiving aspirin.

CONCLUSION: In patients with established cardiovascular disease, clopidogrel was associated with a 17% relative-risk reduction for nonfatal MI, borderline decreased risk for MACE, and similar risk for all-cause mortality, stroke, and major bleeding compared with aspirin.


Discipline Area Score
Neurology 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Cardiology 6 / 7
Hemostasis and Thrombosis 5 / 7
Comments from MORE raters

Cardiology rater

Not ground-breaking but useful info. Used alone, mortality is identical between aspirin and clopidogrel, but the latter results in fewer major adverse CV events including fewer non-fatal MIs.

Family Medicine (FM)/General Practice (GP) rater

A very well done systematic review and meta-analysis that yielded results of uncertain newsworthiness. The key result is that Clopidogrel is at least as good as aspirin for secondary prevention of adverse cardiovascular events and potentially is a little better for preventive nonfatal MIs (relative risk reduction of 17%, NNT 217 for 20 months to prevent one event). The authors appropriately hesitate to claim anything definitive given the rather different study populations, event definitions, and aspirin doses used in their 5 studies. It seems like there is still room for future research to clarify the magnitude of the difference between these agents, if any exists.

General Internal Medicine-Primary Care(US) rater

Fascinating parallel with secondary stroke prevention where clopidogrel has a similar RRR relative to aspirin monotherapy. Although ARR over 20 months is small, it is not negligible.

Internal Medicine rater

A good review and comparison between aspirin and clopidogrel, however the significance is still questionable as the confidence interval values are so close to 1. It does raise the important question of whether clopidogrel will be cost-effective compared with aspirin, especially when there is bleeding risk and perioperative risk involved.

Internal Medicine rater

Nice to put it together.
Comments from EvidenceAlerts subscribers

Dr. Thomas Baitz (8/18/2022 9:26 AM)

Finally proven 20 years too late! Unfortunately, the economic impact is not addressed. Another article? In today’s world, we need to discuss overall healthcare - and not just a fraction of it.