Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack

Kyuho Kim, Mercer University College of Pharmacy

 

The morbidity of ischemic stroke is the consequence of interaction between the resulting neurological impairment and the high risk for recurrence. An additional plenty of adults experience a transient ischemic attack (TIA). Even if a TIA leaves no immediate impairment, affected individuals have a high risk for future ischemic events, particularly in the days and weeks immediately after symptom resolution. [1]

 

The risk of following ischemic events is considered to be high during the first 90 days after the index cerebrovascular event and aspirin at a dose of 50 to 325 mg daily is commonly used in this context. However, the benefit of aspirin in the secondary prevention of ischemic stroke is limited; even with simultaneous aspirin treatment, the rate of recurrent stroke is 10 to 15% in the first 90 days. In addition, it is stated that even moderate doses of aspirin are related to relative risks of hemorrhagic events. [2]

 

To reduce the risk of recurrent ischemia after transient ischemic attack or acute ischemic stroke, it is stated that intensive antiplatelet therapy through a different mechanism of action is considered to be more effective than aspirin, but evidence to support this is limited. Ticagrelor is considered to be a potent antiplatelet agent. [3]

 

Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack
Design Multicenter, randomized, double-blind, double-dummy, parallel-group trial; N= 13,199
Objective To compare ticagrelor with aspirin regarding their effectiveness for the prevention of major vascular events over a period of 90 days in the treatment of patients with acute cerebral ischemia
Study Groups Ticagrlor 180mg twice daily (n= 6,589); aspirin 100mg once daily (n= 6,610)
Methods Total 13,199 patients with a non-severe ischemic stroke or high-risk transient ischemic attack were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90).
Duration January 7, 2014 through October 29, 2015
Primary Outcome Measure Time from randomization to first occurrence of any event from the composite of stroke (ischemic or hemorrhagic), MI, and death
Baseline Characteristics Characteristic Ticagrelor (n= 6,589) Aspirin (n= 6,610)
Age- yr. 65.8 +/- 11.23 65.9 +/- 11.37
Race- no. (%)
White 4,374 (66.4) 4,410 (66.7)
Black 119 (1.8) 120 (1.8)
Asian 1,957 (29.7) 1,949 (29.5)
Medical history- no. (%)
Hypertension 4,797 (72.8) 4,933 (74.6)
Previous ischemic stroke 765 (11.6) 828 (12.5)
Previous TIA 410 (6.2) 446 (6.7)
Coronary artery disease 573 (8.7) 571 (8.6)
Congestive heart failure 234 (3.6) 248 (3.8)
Results Outcome Ticagrelor (n= 6,589) Aspirin (n= 6,610) Hazard ratio (95% CI) p- value
No. of patients (%) Event rate No. of patients (%) Event rate
Stroke, myocardial infarction, or death 442 (6.7) 6.8 497 (7.5) 7.5 0.89 (0.78-1.01) 0.07
Adverse Events Common Adverse Events: N/A
Serious Adverse Events:

Nervous system disorders- ticagrelor (2.5%), aspirin (2.5%)

Cardiac disorders- ticagrelor (1.3%), aspirin (1.0%)

Infections and infestations- ticagrelor (1.2%), aspirin (0.9%)

Percentage that Discontinued due to Adverse Events: ticagrelor (9.7%), aspirin (7.1%)
Study Author Conclusions Ticagrelor was not found to be superior to aspirin in reducing the risk of the composite end point of stroke, myocardial infarction, or death.

 

This randomized double-blind trial showed that events including a composite of stroke, myocardial infarction, or death were more common among patients who received ticagrelor than among patients who received aspirin in the secondary prevention in patients with noncardioembolic ischemic stroke and transient ischemic attack.

 

Despite the negative results on the primary outcome, there were some signals within subgroups suggesting that further study of ticagrelor could be warranted. In particular, they found no signs of increased hemorrhage or other safety issues in the ticagrelor arm of the study.

 

While the trial aimed to test monotherapy ticagelor and aspirin, approximately one-third of the patients were taking aspirin at the time of the qualifying event. Further study of the combination of ticagrelor and aspirin may be warranted, given the possibility that the rates of ischemic stroke were lower in association with ticagrelor in this group of patient.

 

 

 

References

 

  1. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-2236
  2. Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-1860
  3. Ghazaleh G. et al. Antiplatelet Treatment for Prevention of Cerebrovascular Events in Patients With Vascular Diseases; A Systematic Review and Meta-Analysis. 2014;45:492-503

 

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s