Ticagrelor cuts MACCE, major bleeding rates, but contributes to increased minor bleeding

The use of ticagrelor in acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention appears to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) without increasing major bleeding episodes when compared with clopidogrel, although the former antiplatelet strategy may heighten the risk of minor bleeding, according to a study.

Older age, use of tirofiban and use of low-molecular-weight heparin are the key factors responsible for the unfavourable minor bleeding outcome with ticagrelor, the investigators pointed out.

The current retrospective analysis involved 1,083 ACS patients with recurrent myocardial infarction and were treated with primary angioplasty from a single centre in China. Of these patients, 523 were assigned to the ticagrelor group (180-mg loading dose, 90-mg BID maintenance dose) and 560 to the clopidogrel group (300–600-mg loading dose, 150-mg daily maintenance dose) for the prevention of cardiovascular events.

At the 24-month follow-up, the primary efficacy endpoint of MACCE—defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, and stroke—occurred significantly less frequently with ticagrelor than with clopidogrel (10.5 percent vs 13.2 percent; hazard ratio [HR], 1.252, 95 percent confidence interval [CI], 1.141–1.683; p=0.023). [Clin Ther 2019;doi:10.1016/j.clinthera.2019.08.007]

On stratified analyses, MACCE was associated with older age, diabetes, involvement of the left main artery, triple-vessel artery disease, and use of glycoprotein IIb/ IIIa inhibitors, such that patients with these characteristics had lower MACCE risk with ticagrelor vs clopidogrel.

The incidence of major bleeding complications classified according to the Thrombolysis In Myocardial Infarction (TIMI) did not differ between the two treatment groups (HR, 1.231, 95 percent CI, 0.586–1.896; p=0.14), indicating that ticagrelor did not elevate the risk of major bleeding.

However, TIMI-defined minor bleeding rate was higher in the ticagrelor vs clopidogrel group (18.1 percent vs 15.3 percent; HR, 0.654, 95 percent CI, 0.421–0.743; p=0.008). Survival analysis showed that clopidogrel factored in lower major and minor bleeding rates (p=0.015 and p<0.001, respectively).

Bleeding events were strongly associated with the age, tirofiban use and low-molecular-weight heparin use. Specifically, the rate of bleeding was lower with clopidogrel in patients aged >75 years (HR, 0.622, 95 percent CI, 0.315–0.799; p<0.001) and receiving tirofiban (HR, 0.708, 95 percent CI, 0.369–0.905; p=0.011) or low-molecular-weight heparin (HR, 0.445, 95 percent CI, 0.321–0.809; p=0.029).

“Our findings differ from those of a previous study, which showed that ticagrelor is associated with significantly higher rates of clinically relevant haemorrhagic complications and increased thromboembolic and ischemic cardiac events among triple therapy-treated patients. We reviewed our patient information and found that race may be an important contributor to this finding,” according to the investigators, who pointed out that the previous study enrolled few Asian patients. [Cardiovasc Drugs Ther 2018;32:287-294]

“Survivors of ACS have a high risk of recurrent events, and these patients to some extent are at high ischaemic risk; ticagrelor, as a stronger potent antiplatelet agent, may benefit patients… We also found that patients with diabetes may benefit more from ticagrelor, a result of the relatively high ischaemic risk,” they added.

The study was limited by factors inherent to a retrospective analysis, the inclusion of patients treated with primary angioplasty from a single centre in China, and the inability to factor into consideration that the patients might have switched from clopidogrel to ticagrelor or vice versa during the follow-up.