For patients with a moderate-size stroke, bewitch pleasure in ticagrelor plus aspirin became the identical as for patients with minor stroke, a recent exploratory prognosis of the Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial presentations.
Senior THALES investigator Claiborne Johnston, MD, dean, Dell Medical College of the University of Texas at Austin, rapid Medscape Medical Records that two earlier trials of dual antiplatelet treatment for stroke patients safe proven benefits of clopidogrel plus aspirin for patents with minor stroke (Nationwide Institutes of Health Stroke Scale [NIHSS] web, 0–3). The THALES trial included both patients with minor stroke and patients with moderate stroke (NIHSS, 0–5), which became a broader cohort.
“The THALES trial confirmed ticagrelor plus aspirin vs aspirin on my own diminished vascular events with a small develop bigger in hemorrhage probability within the total population included. The ask we checked out in this prognosis is whether or no longer ticagrelor became also of revenue within the moderate-stroke patients (NIHSS, 4–5) as smartly because the minor-stroke patients,” Johnston acknowledged.
The findings had been printed online July 9 in JAMA Neurology.
Bleeding Risk?
There has been field that dual antiplatelet treatment might perchance well perchance well develop bigger hemorrhage probability, particularly intracranial hemorrhage attributable to a bleed into the preliminary infarction, amongst patients with better stroke, acknowledged Johnston.
The present prognosis confirmed that for patients with better NIHSS scores (4 and 5), the bewitch pleasure in ticagrelor plus aspirin vs aspirin on my own became the identical as for patients with decrease NIHSS scores.
“There became no distinction in efficacy or probability of bleeding between the easier- and decrease-probability patients, with benefits outweighing probability in patients with both moderate and minor stroke,” he famend.
At this time, dual antiplatelet treatment is no longer rapid for patients with better infarctions (NIHSS scores of ?6) on story of of concerns about bleeding. THALES is the important stroke trial to consist of patients with NIHSS scores of 4 or 5 in a dual antiplatelet treatment trial, Johnston added.
The THALES trial when put next ticagrelor (180-mg loading dose on day 1 adopted by 90 mg twice every day on days 2 to 30) with placebo within 24 hours after onset of stroke signs. All patients received aspirin 300–325 mg on day 1 adopted by aspirin 75–100 mg every day on days 2 to 30.
Sufferers had been noticed for 30 additional days. The foremost consequence became time to stroke or loss of life within 30 days. The foremost safety consequence became time to severe bleeding.
The present prognosis when put next patients with moderate stroke (baseline NIHSS web, 4 or 5) with patients with minor stroke (NIHSS web, 0–3). A total of 9983 patients with stroke had been included; 3312 patients had moderate stroke, and 6671 had minor stroke.
Results confirmed that the advantages of ticagrelor had been identical for both moderate-stroke and minor-stroke patents.
The noticed important consequence match rate for patients with moderate stroke became 7.6% for these within the ticagrelor community and 9.1% for these within the placebo community (hazard ratio, 0.84; 95% CI, 0.66 – 1.06). The foremost consequence match rate for patients with much less severe stroke became 4.7% for these within the ticagrelor community and 5.7% for these within the placebo community (hazard ratio, 0.82; 95% CI, 0.66 – 1.01). The P worth for interaction became .88.
Extreme bleeding came about in eight patients (0.5%) within the ticagrelor community and in four patients (0.2%) within the placebo community amongst these with moderate stroke, when put next with 16 patients (0.5%) and three patients (0.1%), respectively, amongst these with minor severe stroke (P for interaction = .26).
Thanks to the small increased probability for severe bleeding proven within the total THALES trial, there has been vital discussion on whether the revenue outweighs the probability for all patients.
Undertreated Population
Johnston acknowledged, “While this hasn’t fully been resolved but, we haven’t came across a subgroup who shouldn’t be handled with ticagrelor.
“This prognosis now provides evidence supporting ticagrelor in these patients with moderate stroke. This became the community for which there became the most field over bleeding probability, but even in this community, ticagrelor appears like priceless,” he added.
Ticagrelor now turns into the handiest antiplatelet to safe proven revenue when added to aspirin for patents with moderate stroke. For patients with minor stroke (NIHSS, 0–3), both clopidogrel and ticagrelor safe proven revenue.
Asked how to determine on from these two medicine for patients with minor stroke, Johnston acknowledged this ask is peaceable unresolved for the time being.
“Clopidogrel might perchance well perchance well additionally be influenced by genetic variations that might perchance compromise its efficacy, but we want more files on that,” he famend.
The CHANCE-2 trial is due to the document soon on this field. That trial is comparing clopidogrel with ticagrelor for patients who elevate the clopidogrel loss-of-effectiveness gene.
“The effort is, we don’t know if patients elevate this gene after they want to be handled abruptly after having a stroke. The genetic checks bewitch time, but we want to originate treatment abruptly,” Johnston outlined.
“On the more than a few hand, the clopidogrel files had been out for longer, there are two trails available within the market (CHANCE and POINT), and the pointers replicate that with a stronger level of evidence. So more clinicians presumably employ clopidogrel for these causes,” he acknowledged.
“Shall we peaceable no longer be spending too vital time being concerned about which of these two agents to employ. Pretty, the largest thing is that patients bewitch one among them. Nonetheless here is no longer happening in many patients. Now we safe to work more durable to web more patients handled,” he stressed.
Underrecognized Risks?
Commenting on the findings for Medscape Medical Records, David Spence, MD, professor of neurology and medical pharmacology at Western University and director of the Stroke Prevention and Atherosclerosis Research Center, Robarts Research Institute, London, Ontario, Canada, acknowledged the outcomes are what he would safe expected.
As to which agent to determine on, Spence device out that handiest clopidogrel is reimbursed to be used in stroke in Ontario, but he believes the considerations with clopidogrel are underrecognized.
“Roughly 30% of Europeans and better than half of Chinese folks safe the loss-of-just variant that ends in diminished efficacy of clopidogrel. So, in my detect, we ought to be the utilization of ticagrelor or prasugrel in want to clopidogrel,” he acknowledged.
“I notify dyspnea is a device with ticagrelor, and there might perchance be latest evidence that in acute coronary syndrome, prasugrel became more efficacious, so if I had my different, I would prescribe prasugrel,” he added.
Spence believes bleeding problems might perchance well perchance well be markedly diminished by correct sanatorium treatment.
“Intracerebral hemorrhage is virtually eradicated by correct blood stress withhold an eye on, and presumably most of the important gastrointestinal bleeds might perchance well perchance well be shunned by detecting and treating Helicobacter pylori. Antiplatelet agents and anticoagulants attain no longer build off bleeding to originate; they build off bleeding now to not quit,” he famend.
The THALES trial became funded by AstraZeneca. Johnston led the POINT trial of clopidogrel in stroke. He has received grants from AstraZeneca and Sanofi. Spence has disclosed no connected monetary relationships.
JAMA Neurol. Printed online July 9, 2021. Beefy textual divulge
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