Dual antiplatelet therapy (DAPT) with aspirin and either ticagrelor or clopidogrel was superior to aspirin alone for preventing recurrent strokes or death up to 90 days, but no statistically significant difference was found between ticagrelor and clopidogrel, according to a study published in JAMA Neurology.

Patients with acute minor ischemic stroke and transient ischemic attack (TIA) have an increased risk for recurrent stroke. In the 3 months following a minor stroke or TIA, 10% to 20% of patients experience a recurrent stroke. Previous research suggests DAPT with clopidogrel and aspirin is more effective than antiplatelet monotherapy for secondary stroke prevention in this patient population. This prompted a revision in guideline recommendations from various organizations, including the American Heart Association Guidelines for the Prevention of Stroke in Patients With Stroke and TIA.

The objective of the current study was to conduct a systematic review and network meta-analysis using available evidence to compare the relative efficacy and safety of ticagrelor and aspirin vs clopidogrel and aspirin in patients with acute minor ischemic stroke and TIA.


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They searched the MEDLINE, Embase, and Cochrane Registry of Clinical Trials and included articles from database inception until February 2021. Eligible studies were randomized clinical trials (RCT) that provided the interventions within 72 hours of symptom onset with a minimum follow-up of 30 days.

The primary outcome was recurrent stroke or death at 90 days, and secondary outcomes included individual components of the composite outcome.

A total of 4014 unique titles and abstracts were screened, and 9 articles met eligibility for extraction, with 5 RCTs and 4 subgroup analyses. Data from 22,098 individuals were assessed: 10,722 received aspirin, 5517 received clopidogrel and aspirin, and 5859 received ticagrelor and aspirin. Participants had comparable mean and median ages in all the studies.

Clopidogrel and aspirin and ticagrelor and aspirin were more effective for preventing stroke or death compared with aspirin alone (clopidogrel: hazard ratio [HR], 0.74; 95% credible interval [CrI], 0.65-0.84; ticagrelor: HR, 0.79; 95% CrI, 0.68-0.91). No significant difference was found in a comparison of clopidogrel and aspirin with ticagrelor and aspirin (HR, 0.94; 95% CrI, 0.78-1.13).

Clopidogrel and aspirin and ticagrelor and aspirin led to a significant increase in major hemorrhage vs aspirin alone (clopidogrel: HR, 1.78; 95% CrI, 1.09-2.92; ticagrelor: HR, 2.63; 95% CrI, 1.51-4.82).

Clopidogrel and aspirin was associated with a lower risk of 90-day functional disability vs aspirin alone and vs ticagrelor and aspirin (clopidogrel: HR, 0.82; 95% CrI, 0.74-0.91; ticagrelor: HR, 0.85; 95% CrI, 0.75-0.97).

No difference was observed in the risk of 90-day mortality or adverse events among any of the treatment regimens.

Sensitivity analysis showed that in a comparison with aspirin, clopidogrel and aspirin as well as ticagrelor and aspirin were associated with a significant decrease in recurrent stroke or mortality at 30 days (clopidogrel: HR, 0.68; 95% CrI, 0.59-0.79; ticagrelor: HR, 0.82; 95% CrI, 0.71-0.95). No significant difference was found for clopidogrel and aspirin vs ticagrelor and aspirin (HR, 0.83; 95% CrI, 0.68-1.02).

Among several study limitations, the researchers noted that they focused on RCTs and may have overlooked other data and that the treatment durations differed in the trials. Also, owing to incomplete reporting of specific outcomes across trials, the researchers were unable to report their prespecified primary outcome of ischemic stroke alone at 30 days. Furthermore, residual clinical and statistical heterogeneity may exist among the trials.

“Our study suggests aspirin and ticagrelor is a reasonable alternative to aspirin and clopidogrel where there is clopidogrel failure or intolerance,” stated the researchers.

Disclosure: One of the study authors declared an affiliation with a global commercial services company. Please see the original reference for a full list of authors’ disclosures.

Reference

Lun R, Dhaliwal S, Zitikyte G, Roy DC, Hutton B, Dowlatshahi D. Comparison of ticagrelor vs clopidogrel in addition to aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis. JAMA Neurol. Published online December 6, 2021. doi: 10.1001/jamaneurol.2021.4514