Balint A, Tornyos D, El Alaoui El Abdallaoui O, et al. Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events. Stroke. 2021 Jun 24:STROKEAHA120032670. doi: 10.1161/STROKEAHA.120.032670.

BACKGROUND AND PURPOSE: Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease.

METHODS: Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality.

RESULTS: Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71-0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77-1.00]; P=0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91-1.07]).

CONCLUSIONS: Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Internal Medicine
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Hemostasis and Thrombosis
Public Health
Comments from MORE raters

Cardiology rater

Relevant information in the realm of DAPT for stroke prevention becoming more common.

Hemostasis and Thrombosis rater

Ticagrelor plus ASA may lead to fewer strokes but more major bleeding (including ICH) compared with single-agent regimens. It would have been helpful to also present absolute rates as it is difficult to assess the clinical impact of the relative changes.

Internal Medicine rater

P2Y12 inhibitor ticagrelor for vascular disease might have better CV protection at the expense of more bleeding. Individual patient decisions would have to be made.