P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack

Abstract

Background and purpose: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. Methods: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I 2 test. Results: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68–0.83], I 2 =0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89], I 2 =0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17], I 2 =0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29], I 2 =94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39], I 2 =0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08], I 2 =41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75–4.67], I 2 =0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08], I 2 =37%) but not within 21 days or clopidogrel. Conclusions: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

Non-stenotic Carotid Plaques in Embolic Stroke of Unknown Source

“…and Death (THALES) trial(109)(110)(111)(112). The ongoing Clopidogrel with Aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2, NCT04078737) trial is evaluating the superiority of the Ticagrelor-Aspirin combination over Clopidogrel-Aspirin therapy in CYP2C19 loss of function carriers with minor stroke or transient ischemic attack (TIA)(113).AnticoagulationTheNew Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA [Acetylsalicylic Acid] to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) and the Randomized Double-Blind Evaluation in Secondary Stroke Prevention Comparing The Efficacy Of Oral Thrombin Inhibitor Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT-ESUS) trials have shown that universal full-dose oral anticoagulation is not an effective strategy to reduce the risk of stroke recurrence in patients with ESUS(5,6).…”

Perspective on management of Transient Ischemic Attack in the emergency department

“…11 Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor is more effective than aspirin alone for the prevention of recurrent stroke. 12 A meta-analysis also concluded the effectiveness of DAPT however there is a higher risk of major bleeding which needs to be assessed during therapeutic strategies. 13 In a study conducted in Ottawa Hospital, Ontario , Canada there was however no statistical difference between clopidogrel and ticagrelor for the primary outcome of TIA.…”

Dual antiplatelet instead of intravenous thrombolysis for minor nondisabling acute ischemic stroke: A perspective from China

“…Despite the slight variation in the definition of minor stroke between the CHANCE or POINT trial (NIHSS score 0–3) and the ARAMIS trial (NIHSS score 0–5), a meta-analysis has demonstrated the superiority of DAPT over aspirin monotherapy in patients with minor stroke or high-risk transient ischemic attack, irrespective of the NIHSS score for minor stroke. [ 16 ] The determination of the loading dose of antiplatelet drug is of utmost importance in ensuring safety. In the ARAMIS trial, the clopidogrel loading dose of DAPT treatment strategy (300 mg) was found to be comparable to that used in the CHANCE trial (300 mg), while differing from the dosage utilized in the POINT trial (600 mg).…”