Efficacy and Safety of Using Dual Versus Monotherapy Antiplatelet Agents in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Abstract

Background: Dual antiplatelet treatment (DAPT) with aspirin plus clopidogrel for a limited time is recommended after minor non-cardioembolic stroke. Methods: We performed a meta-analysis of all major studies that compared the efficacy and safety of DAPT versus monotherapy for secondary prevention of recurrent stroke or transient ischemic attack (TIA). The primary outcomes were stroke and the composite of stroke, TIA, acute coronary syndrome and death of all cause. The safety outcome was major hemorrhage. Relative risk (RR) and 95% confidence intervals (CI) were calculated. Heterogeneity was assessed by I 2 and Cochrane's Q statistics. Results: The analysis included 27358 patients, the quality of evidence was moderate to low, and the heterogeneity for all the comparisons was low (I 2 ≤25%). Compared with monotherapy, DAPT reduced the risk of recurrent stroke (RR=0.71, 95% CI=0.63-0.81) and composite outcome (RR=0.76, 95% CI=0.69-0.83) but increased the risk of major bleeding (RR=2.17, 95% CI=1.45-3.25). In subgroup analysis, ≤30 days DAPT increased the risk of hemorrhage relative to monotherapy (RR=1.94, 95% CI=1.08-3.52). In sensitivity analysis, the risk for hemorrhage with ≤30 days of DAPT after excluding the combination of aspirin plus ticagrelor was comparable to monotherapy (RR=1.42, 95% CI=0.77-2.60). However, the risk for stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remain decreased compared to monotherapy. Conclusions: DAPT decreases the risk of recurrent stroke and composite events compared with monotherapy. DAPT increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus ticagrelor.

Contemporary antiplatelet therapy for secondary stroke prevention: a narrative review of current literature and guidelines

“…Cochrane systematic review, pooled data analysis and meta-analysis of RCTs demonstrated that DAPT with aspirin and clopidogrel or ticagrelor for 21–30 days is more effective than SAPT for secondary stroke prevention when initiated early after the onset of minor stroke or high-risk TIA 3 6–9. However, when initiated later and used longer than 90 days, DAPT increases the risk of bleeding without reduction of stroke recurrence than SAPT 7–9…”

“…The current evidence-based recommendations on antiplatelet therapy for secondary stroke prevention are summarised in table 3 3–10…”

“…Aspirin, clopidogrel, dipyridamole/aspirin, cilostazol and ticagrelor are commonly used antiplatelet agents. In recent years, numerous randomised controlled trials (RCTs), Cochrane systematic reviews and meta-analyses evaluated the efficacy and safety of antiplatelet therapy for secondary stroke prevention 3–9. Due to the complexity of stroke aetiology and diverse mechanisms of antiplatelet agents (figure 1), it is essential to select optimal antiplatelet therapy in the real-world practice.…”

“…Due to the complexity of stroke aetiology and diverse mechanisms of antiplatelet agents (figure 1), it is essential to select optimal antiplatelet therapy in the real-world practice. In this narrative review, we aimed to highlight current evidence and recommendations of the antiplatelet therapy for secondary stroke prevention 2–10…”

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

“…209 Clopidogrel added to aspirin for patients with transient ischemic attack (TIA) or ischemic stroke appears to significantly decrease the risk of ischemic stroke recurrence, but again there is an elevated risk of bleeding vs aspirin alone. [210][211][212] Interestingly, the data in support of clopidogrel monotherapy over other antiplatelet agents is limited by the small numbers of studies that directly compare clopidogrel as single antiplatelet therapy. A meta-analysis of 5 studies indicated that clopidogrel monotherapy for secondary stroke prevention may reduce risks of major adverse CV or cerebrovascular events, recurrent stroke, and bleeding events compared with aspirin.…”