Treatment with clopidogrel with aspirin or ticagrelor with aspirin produces a similar reduction in the risk of recurrent stroke or death.

1. Treatment after a minor stroke or transient ischemic attack with dual antiplatelet therapy (DAPT), either clopidogrel with aspirin or ticagrelor with aspirin, also reduces the risk of stroke. or death, which is more than treatment with aspirin alone.

2. Both DAPTs had a similar risk of major bleeding, 90-day mortality, and adverse event rate, but clopidogrel and aspirin had a greater decrease in risk of disability from stroke.

Level of Evidence Assessment: 1 (Excellent)

Study overview: Having a minor ischemic stroke or transient ischemic attack (TIA) is a risk factor for having a subsequent stroke. Short-term dual antiplatelet therapy (DAPT) using clopidogrel and acetylsalicylic acid (ASA; aspirin) or using ticagrelor and aspirin is known to be better than monotherapy for the secondary prevention of strokes after an AIT. This study aimed to compare the efficacy and safety of the two DAPT protocols. This meta-analysis compared the rates of stroke or recurrent death, functional disability via the modified Rankin scale (mRS), and safety between ticagrelor and aspirin, clopidogrel and aspirin, and aspirin after a TIA or a minor stroke. The pooling of data between the 5 eligible randomized controlled trials (RCTs) and the analyzes of 4 subgroups identified that the use of a DAPT was superior to aspirin alone for the prevention of strokes. and that the two DAPT protocols were similar for the prevention of stroke or death. Specifically, both DAPTs decreased the incidence of ischemic stroke, with clopidogrel having a greater effect. None of the DAPT regimens increased the risk of hemorrhagic stroke. Both DAPTs increased the risk of major bleeding. While DAPTs and aspirin had similar 90-day mortality and adverse event rates, clopidogrel and aspirin were associated with a decreased risk of functional disability compared to aspirin alone. A strength of this meta-analysis is the a priori publication of the research strategy to reduce bias. In addition, it featured a clean meta-analysis, which could rank treatments, unlike other meta-analyzes. One consideration is that this meta-analysis may have overlooked a significant portion of the data by including only RCTs, although it may then claim causal relationships. A limitation of this study is that the treatment durations and follow-up time differed in the different included RCTs, as did the inclusion and exclusion criteria, although only minimally. Finally, there was no assessment of publication bias due to the clear meta-analysis method used.

Click to read the study in JAMA Neurology

Relevant reading: Ticagrelor is superior to clopidogrel in inhibiting platelet reactivity in patients with minor stroke or TIA

In depth [systematic review and meta-analysis]: This meta-analysis averaged the rates of recurrent stroke or death at 90 days in RCTs comparing ticagrelor and aspirin, clopidogrel and aspirin, and aspirin use in adults in 72 hours following a TIA or minor stroke. In addition, he assessed functional disability via mRS and adverse events. RCTs were found in English or French on MEDLINE, Embase, Cochrane Registry of Clinical Trials, World Stroke Congress and International Stroke Conference and selected by two independent reviewers. Bias was assessed using the Cochrane Risk of Bias Tool for Randomized Trials Version 2 (RoB2). 5 RCTs and 4 subgroup analyzes (N = 22,098; 10,722 received aspirin, 5,517 received clopidogrel and aspirin, and 5,859 received ticagrelor and aspirin) responded to the inclusion criteria out of the 4014 unique titles examined. The studies were all at low risk of bias from RoB2. 3 RCTs compared clopidogrel and aspirin with aspirin, 1 RCT compared ticagrelor and aspirin with aspirin, and 1 RCT compared clopidogrel and aspirin with ticagrelor and aspirin, all at similar doses for 21 to 90 days. The included RCTs included participants of similar age and definitions of stroke. Consistent with previous studies, clopidogrel and aspirin were better at preventing stroke or death than aspirin alone (HR = 0.74, 95% Credible Intervals (CrI) = 0.65-0, 84), just like ticagrelor and aspirin (HR = 0.79.95% CrI = 0.68-0.91). Clopidogrel and aspirin were similar to ticagrelor and aspirin in preventing stroke and death (HR = 0.94, 95% CrI = 0.78-1.13). Compared with aspirin alone, clopidogrel and aspirin (HR = 0.71; 95% CrI = 0.62-0.82) and ticagrelor and aspirin (OR = 0.74, 95% CrI = 0.64-0.86) both reduced recurrent ischemic strokes. Clopidogrel showed the best surface under the cumulative rank curve (SUCRA) results, while aspirin alone had the highest risk of ischemic stroke and prevention of death. Neither the DAPT protocol increased the risk of hemorrhagic stroke compared to aspirin, nor one compared to the other (HR = 0.67, 95% CrI = 0.26-1.70) . Ticagrelor and aspirin had the highest risk of hemorrhagic stroke according to SUCRA. Both DAPT protocols increased the risk of major bleeding compared to 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 had a lower risk of disability compared to aspirin alone (HR = 0.82; 95% CrI = 0.74-0.91) and compared to ticagrelor and aspirin ( HR = 0.85.95% CrI = 0.75-0.97). All treatments had comparable 90-day mortality, although ticagrelor and aspirin had the highest SUCRA rate, as well as the highest rate of adverse events. There was no statistically significant difference in reduction of stroke or death on sensitivity analysis between treatment after minor stroke or TIA with clopidogrel and aspirin compared to ticagrelor and aspirin (HR = 0.83, 95% CrI, 0.68-1.02); clopidogrel and aspirin had the lowest risk of stroke recurrence with SUCRA (0.96) compared to ticagrelor and aspirin (0.4) and aspirant (0).

Image: PD

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About Antoine L. Cassell

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