Transient Ischemic Attack and Acute Stroke
- Aspirin is used in treating a neurological condition
called transient ischemic attack (TIA) followed by acute stroke, but the
major adverse effect of bleeding in brain restricts its use in many cases.
- A better, more intensive treatment regimen involving
anti-platelet therapy with a different mechanism of action might be more
effective than aspirin in reducing the risk of transient ischemic attack,
stroke as well as recurrent ischemia.
- Ticagrelor is an oral, reversible drug which leads to
platelet inhibition and helps in blood thinning. It is considered more
effective than clopidogrel in reducing stroke, ischemic attack as well as
cardiac related deaths.
A transient ischemic attack (TIA)
, commonly known as mini stroke, is similar to a stroke, with an exception of shorter duration of onset and lack of permanent brain damage
. In a TIA, the patient has symptoms like blank expression face, blinking eyes repeatedly, licking lips, for a few seconds to minutes. An acute stroke occurs due to sudden bleeding or severely reduced blood supply to brain tissues, leading to oxygen and nutritional deficiency to the delicate brain cells.
‘The randomized trial, SOCRATES, conducted to compare the efficacy of ticagrelor and aspirin in reducing cardiac related mortality rate, ischemic attacks and strokes concluded that ticagrelor is not better than aspirin.’
The incidence of acute stroke
and transient ischemic attack is high; they affect about 795,000 and
200,000 to 500,000 people per year in United States, respectively. Moreover, acute stroke is the second most common cause of death worldwide. It has been seen that a stroke is generally preceded by a transient ischemic attack. Therefore, a transient ischemic attack is considered as an alarm for the patients to follow measures to prevent a stroke
, at a dose of 50 to 325 mg daily, has been found beneficial for patients with occlusive vascular disease. However, its role in reducing occlusive vascular disorders without previous history of disease is limited. Studies report 10-15 % of recurrence after three months of transient ischemic attack. Moderate doses increase the risk of bleeding/hemorrhagic events, including gastrointestinal bleeding. Ticagrelor, a potent anti-platelet agent, is a directly acting drug which reversibly binds and inhibits the P2Y12 receptors on platelets. It is an effective agent for patients with acute coronary syndrome with or without ST-segment elevation. It reduces the mortality rate as well as incidence of acute myocardial infarction
leading to a decreased risk of stroke. Even in patients with a history of myocardial infarction, ticagrelor
has shown good results by reducing the risk of cardiovascular deaths and stroke. Its effect on bleeding is inconclusive as studies report disparate results. However, an increased rate of major bleeding is an adverse effect associated with the use of aspirin.
Clinical Trial (SOCRATES)
A recent study conducted by Johnston et al., 2016 demonstrated the outcomes of Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial which was designed to compare ticagrelor and aspirin as a treatment regimen for acute stroke or transient ischemic attack as well as an agent to prevent major vascular events such as stroke
[ischemic or hemorrhagic], myocardial infarction, or even death. The study was conducted over a 90 day period. The study was conducted at international level enrolling 674 centers in 33 countries, including 13,199 patients with a diagnosed history of non-severe ischemic stroke or high- risk transient ischemic attack. The patients who did not have a history of treatment with intravenous or intra-arterial thrombolysis (dissolution of blood clot) as well as cases with cardioembolic stroke were not included. The participating patients were randomly assigned to receive either ticagrelor at a loading dose of 180 mg followed by 90 mg twice daily till 90 days or aspirin at a loading dose of 300 mg on first day followed with 100 mg daily till 90 days. The treatment was started within 24 hours after onset of symptoms. The time to the occurrence of stroke, myocardial infarction, or death within 90 days was considered as primary end point.
During the 90 days
treatment study, a primary end point was observed in 442/ 6589 patients
receiving ticagrelor, whereas 497 of the 6610 patients treated with aspirin
showed primary end point. Moreover, ischemic stroke was observed in 5.8% and
6.7% patients treated with ticagrelor and aspirin, respectively. Occurrence of
major bleeding, intracranial hemorrhage and fatal bleeding was almost similar
in all the patients - 0.5%, 0.2%, 0.1% in ticagrelor arm and 0.6%, 0.3%, 0.1%
in aspirin arm, respectively. The
results concluded that ticagrelor was not found superior to aspirin in reducing
the rate of stroke, myocardial infarction, or cardiovascular death at 90 days.
It was observed during
the study that patients undergoing aspirin therapy showed better results upon
addition of ticagrelor as a treatment regimen. Scientists might think of
conducting trials including combination therapies using aspirin and ticagrelor
alone or as comparative study against monotherapy. Moreover, an early
treatment, within 12 hours of onset of symptoms, might result in good and more
- Giles MF, Rothwell PM. Risk of Stroke Early After Transient Ischaemic Attack: a Systematic Review and Meta-analysis. Lancet Neurol 2007;6:1063-1072.
- Valkhoff VE, Sturkenboom MC, Hill C, Veldhuyzen van Zanten S, Kuipers EJ. Low-dose Acetylsalicylic Acid Use and the Risk of Upper Gastrointestinal Bleeding: a Meta-Analysis of Randomized Clinical Trials and Observational Studies. Can J Gastroenterol 2013;27:159-167.
- Johnston SC, Amarenco P, Albers GW, et al. Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: Rationale and Design. Int J Stroke
- Wallentin L, Becker RC, Budaj A, et al. Ticagrelor Versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2009;361:1045-1057.
- Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor Versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med 2016;375:35-43.
- Epidemiology, Risk Factors, Pathophysiology and Causes of Transient Ischemic Attacks and Stroke. - (http://assets.cambridge.org/97805217/35124/excerpt/9780521735124_excerpt.pdf)