EvidenceAlerts

COVID-19 COVID-19 Evidence Alerts from McMaster PLUS is a new service that alerts users to current best evidence for clinical care of people with threatened, suspected or confirmed COVID-19 infection.
Visit the site Sign up for alerts
Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870. (Original study)
Abstract

BACKGROUND: Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.

METHODS: We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.

RESULTS: A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).

CONCLUSIONS: Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score =5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).

Ratings
Discipline Area Score
Hospital Doctor/Hospitalists 7 / 7
Internal Medicine 7 / 7
Neurology 7 / 7
Emergency Medicine 5 / 7
Comments from MORE raters

Emergency Medicine rater

This industry-sponsored, placebo-controlled, double-blind RCT evaluated treatment for secondary stroke prevention. Patients included those with acute minor stroke (NIHSS score =< 5) or high-risk TIA starting within 24 hours before enrollment. They did not receive thrombolytic therapy or require anticoagulation. Patients were randomized to receive aspirin alone or aspirin plus ticagrelor. The primary outcome was a composite of stroke or mortality within 30 days. 11,016 patients underwent randomization. The primary outcome occurred in 5.5% of patients in the ticagrelor plus aspirin group and 6.6% in the aspirin alone group. Severe bleeding occurred in 0.5% of patients in the combined therapy group versus 0.1% of patients in the aspirin-alone group. The results are similar to previous studies evaluating aspirin with clopidogrel. Physicians must balance the risk for bleeding with stroke prevention.

Emergency Medicine rater

Landmark stroke trial of particular interest to emergency and other acute care providers. The treatment benefits are small and bleeding risk is not insignificant. The landscape has become particularly complex with the recent Chinese trial examining the same question but with clopidogrel. Still no direct comparison on the optimal approach to dual anti-platelets, but this could be clarified as the editorial seeks to do.

Internal Medicine rater

The issue is important but I still would not be sure what to do: take a 1% decreased risk for a recurrent stroke (at what level of severity?) vs a 0.4% increased risk for an intracranial hemorrhage or fatal bleeding (something you can be sure was a very severe outcome)? Multiply this by taking a second med and this is then associated with other adverse effects, either previously unrecognized drug-drug interactions, or something as simple as increasing the complexity of the drug regimen with the patient then becoming less compliant on something else, like, say, their statin or HTN meds.

Internal Medicine rater

A very confusing area with mixed results.

Neurology rater

The clinical trial tested dual antiplatelet therapy of ticagrelor plus aspirin with aspirin alone in short-term risk for stroke or death (90 days) after a minor stroke or high-risk TIA. The results are mixed: dual antiplatelet regimen was associated with a small absolute risk reduction in ischemic stroke by 1.3%, but with absolute risk increase of 0.4% of severe bleeding. Therefore, it does not immediately change practice, but it is important information as ticagrelor is common and used in coronary artery disease.
Comments from EvidenceAlerts subscribers

No subscriber has commented on this article yet.