For discussion with your doctor and while you are at it ask what the 30-day death rate is at their hospital. No knowledge, fire them, because it means they don't care about or know what the fuck they are doing.
— THALES trial supports addition to aspirin but comparison with clopidogrel now needed
by
Nicole Lou, Staff Writer, MedPage Today
July 15, 2020
For acute ischemic strokes, early treatment with
ticagrelor (Brilinta) and aspirin was better than aspirin alone for
secondary prevention, the THALES trial showed.
In people with mild-to-moderate acute ischemic stroke or transient
ischemic attack (TIA),
the composite outcome of stroke or death in the
30 days after randomization favored a 30-day regimen of ticagrelor plus
aspirin over aspirin alone (5.5% vs 6.6%, HR 0.83, 95% CI 0.71-0.96).
This was driven by fewer ischemic strokes (5.0% vs 6.3%, HR 0.79, 95%
CI 0.68-0.93), with no significant difference in mortality rates
between groups (0.7% vs 0.5%, HR 1.33, 95% CI 0.81-2.19). Disability
rates didn't differ significantly.
The
dual antiplatelet group experienced more severe bleeding by GUSTO
criteria (0.5% vs 0.1%, HR 3.99, 95% CI 1.74-9.14) and more intracranial
hemorrhage (0.4% vs 0.1%, HR 3.33, 95% CI 1.34-8.28), reported the
investigators, led by S. Claiborne Johnston, MD, PhD, of Dell Medical
School of the University of Texas at Austin.
A full manuscript of the study was published in the July 16 issue of the
New England Journal of Medicine. Topline data were
previously announced by trial sponsor AstraZeneca.
"The benefit from treatment with ticagrelor-aspirin as compared with
aspirin alone would be expected to result in a number needed to treat of
92 to prevent one primary-outcome event and a number needed to harm of
263 for severe bleeding," the researchers concluded.
"Based on these results, plus the higher severe bleeding with
ticagrelor, and greater expense, I don't think ticagrelor will replace
clopidogrel [Plavix] as part of the dual antiplatelet regimen used after
high risk TIA or minor stroke," commented James Grotta, MD, of Memorial
Hermann-Texas Medical Center in Houston.
The
CHANCE-2 trial
directly comparing ticagrelor against clopidogrel as the add-on to
aspirin is ongoing. Until then, it is "hard to compare" these drugs
without a head-to-head comparison, Grotta said.
Nevertheless, the
POINT and
CHANCE
studies suggested larger relative reductions in the risk of recurrent
ischemic stroke with clopidogrel-aspirin compared to THALES'
ticagrelor-aspirin, according to Peter Rothwell, MD, PhD, of University
of Oxford, England, writing in an
editorial.
Moreover, the risk in major bleeding was increased to a greater
extent with the ticagrelor combination than the clopidogrel one,
particularly with respect to intracranial hemorrhage, Rothwell
continued.
Finally, clopidogrel-aspirin resulted in a significant reduction in
risk of disabling or fatal stroke versus aspirin alone in a pooled
analysis of the POINT and CHANCE trials, whereas ticagrelor-aspirin did
not achieve the same in THALES, he noted.
Grotta said he would have expected the ticagrelor-aspirin combination
to have produced greater benefit over aspirin than what was seen with
clopidogrel-aspirin given the
genetic polymorphism for clopidogrel response.
"Regardless
of which combination of antiplatelet drugs is favored for the high-risk
minority, all patients should receive aspirin immediately after TIA
unless aspirin is contraindicated. Too many patients are sent home from
emergency departments without this simple treatment that substantially
reduces the risk and severity of early recurrent stroke," Rothwell
urged.
THALES
included 11,016 participants who presented with acute ischemic stroke
(NIH Stroke Scale score 5 or less) or high-risk TIA at 414 sites in 28
countries who were not undergoing thrombolysis or thrombectomy.
People were randomized within 24 hours after symptom onset. They
either received a 30-day regimen of ticagrelor (180-mg loading dose,
followed by 90 mg twice daily) plus aspirin (300-325 mg on the first
day, followed by 75-100 mg daily) or matching placebo plus aspirin.
Baseline characteristics were similar between study arms. Mean age was 65 years, and 39% of the participants were women.
People already on aspirin before their index stroke or TIA accounted for 13% of the group.
Johnston
and colleagues noted the limited generalizability of THALES to excluded
populations, namely those with more severe strokes, cardioembolic
strokes, and people who had treatment initiated more than 24 hours after
symptom onset. Patients with a history of atrial fibrillation were also
excluded.
"The bleeding risk associated with ticagrelor and aspirin might
exceed the benefit among lower-risk patients who make up the majority in
practice, and so the current trial results should not be
overgeneralized," Rothwell cautioned.
Ticagrelor was
first approved by the FDA in 2011 for the indication of thrombotic event risk reduction in people with acute coronary syndrome.
Last month, the P2Y12 inhibitor won an
expanded indication to reduce risk of a first heart attack or stroke in high-risk patients with coronary artery disease.
-
Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine.
Follow
Disclosures
The trial was funded by AstraZeneca, which also analyzed the data.
Johnston reported receiving an institutional grant from AstraZeneca.
Rothwell disclosed receiving personal fees from Bayer and BMS.
Primary Source
New England Journal of Medicine
Secondary Source
New England Journal of Medicine
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