Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events

Abstract

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.

Left Ventricular Ejection Fraction Association with Acute Ischemic Stroke Outcomes in Patients Undergoing Thrombolysis

“…In the preventive treatment of LVSD, especially in AIS patients with strong cardiovascular risk factors such as AF and IHD, newer studies support the use of combination antiplatelet and anticoagulant therapy in cardiovascular prevention [ 58 , 59 ], with some stressing the importance of antiplatelet therapy [ 60 ] and even antithrombotic therapy [ 61 ]. Admittedly, this might further increase the risk of complications, such as heightened bleeding risk, especially in the AIS patient population undergoing IV thrombolysis [ 62 ].…”

Combination of antiplatelet and anticoagulant therapy, component network meta-analysis of randomized controlled trials

“…Therefore, the influence of individual components was intended to be evaluated in an additive model assuming that the effect of treatment combinations is the sum of the effects of its components. For CNMA a model implementing an additive model function was used ( 14 , 15 ).…”

“…The assumption of consistency was assessed by net-heat plots as well as by net-splitting. The latter method splits our network estimates into the contribution of direct and indirect evidence, which allows us to control for inconsistency in specific comparisons ( 15 ).…”

The Effect of Platelet Activity, ABCB1 Genetic Polymorphism, and Renal Function on the Development of Ticagrelor-Related Dyspnea in Patients with Acute Coronary Syndrome

“… 1 , 2 , 4 New data suggest that Ticagrelor in combination with aspirin provide more favorable outcomes not only for ACS patients who underwent PTCA with stent implantation, but also for secondary stroke prevention in patients with vascular risk factors. 5 …”