TAPIS: a positive trial in a defined phenotype.

# TAPIS: a positive trial in a defined phenotype *The Lancet 2026* Comment TAPIS: a positive trial in a defined phenotype Clinical trials in stroke balance a few tensions including aggregation is likely to drive post-lytic treatment efficacy against safety, biology against clinical proof, failure. Cohorts elsewhere, with different stroke causes and broad answers against a disease that is not really and genetics, would have a different underlying stroke one disease. Antiplatelet therapy after intravenous biology. Early platelet inhibition was therefore, in the thrombolysis is one such area. Platelet-mediated TAPIS cohort, better matched to the disease.1 re-occlusion after lysis is biologically plausible, but The EAST trial2 assessed early oral dual antiplatelet haemorrhage risk has warranted caution against therapy within 6 h of thrombolysis in patients with early antiplatelet use. In The Lancet, Anxin Wang and minor stroke and showed no benefit (mRS score 0–1 colleagues1 report results from the TAPIS trial, which at 90 days 89·7% vs 89·6%). The contrast with TAPIS reopens this question. is informative. Both trials were done in Chinese Published Online May 8, 2026 TAPIS enrolled 1382 patients from China with acute populations with high CYP2C19 loss-of-function https://doi.org/10.1016/ S0140-6736(26)00820-2 ischaemic stroke (991 [71·7%] male and 391 [28·3%] prevalence, so the difference in result cannot be See Articles page 1919 female; median age 65·6 years; median National attributed to genetic background. The two trials differed Institutes of Health Stroke Scale score of 6) treated with in drug choice (TAPIS used ticagrelor and EAST used alteplase or tenecteplase within 4·5 h and randomly clopidogrel) and in the population studied. Ticagrelor assigned patients to ticagrelor plus aspirin or placebo bypasses CYP2C19 activation, clopidogrel does not, so within 6 h of symptom onset. The causal mix was the EAST regimen was pharmacologically blunted in distinctive: 569 (41%) with large-artery atherosclerosis, this population. EAST also enrolled patients with minor 736 (53%) with small-artery disease, and ten (<1%) stroke, where the proportion of patients with 90-day with cardioembolic stroke. The primary outcome was mRS scores of 0–1 in the placebo group reached 89·6%, excellent recovery at 90 days (modified Rankin Scale leaving little room for benefit.2 [mRS] score 0–1), which occurred in 474 (68·7%) of Looking across other previous trials, timing and type 690 patients in the treatment group versus 429 (62·0%) of antiplatelet administration might matter more than of 692 patients in the placebo group (risk ratio 1·11 stroke severity. ARTIS3 gave intravenous aspirin during [95% CI 1·03–1·20]; p=0·0089).1 the lysis window and produced excess haemorrhage This finding is clinically meaningful but does not (4·3% vs 1·6%) without benefit. MOST4 delivered refute long-standing caution around antiplatelet intravenous argatroban or eptifibatide within 75 min of therapy after thrombolysis. TAPIS is better interpreted lysis and was stopped for futility, with 90-day mortality as a positive trial in a biologically coherent phenotype. of 24% with argatroban, 12% with eptifibatide, and Most participants (984 [71%]) received the study drug 8% with placebo. ASSET-IT5 and TAPIS,1 by contrast, after intravenous thrombolysis was already complete, delivered different antiplatelet therapies after the at a median of 65 min from lytic start. Both groups lytic had been substantially delivered: tirofiban within received open-label aspirin from day 2 until day 90. In 60 min of thrombolysis completion in ASSET-IT, oral practical terms, the trial tested whether adding 7 days ticagrelor and aspirin at a median of 65 min after lytic of oral ticagrelor plus aspirin soon after lysis improves initiation in TAPIS. Oral administration in TAPIS probably outcomes when compared with standard aspirin 24 h delayed peak platelet inhibition further, well beyond afterwards. the lytic window. Both trials enrolled patients with The key question after TAPIS is in which patients the moderately severe, largely non-cardioembolic disease, balance of thrombosis and haemorrhage becomes and both were positive.5 These trials suggest that benefit favourable. Every stroke trial samples a particular emerges when a potent antiplatelet reaches a vascular combination of phenotype of stroke. TAPIS sampled bed after the lytic window has closed, in patients in a population defined by intracranial atherosclerosis whom platelet aggregation drives early re-thrombosis. (including when the stroke was likely classified as The rescue-therapy imbalance in TAPIS supports this small vessel disease), low cardioembolism, and high hypothesis because 50 (7%) of 690 patients in the dual- CYP2C19 loss-of-function prevalence, in which platelet antiplatelet group required rescue tirofiban for early 1892 segamI ytteG aiv nedragnwo Comment neurological deterioration versus 81 (12%) of 692 in trial that sharpens the question, suggesting early the placebo group, a nearly 40% relative reduction and platelet inhibition after intravenous thrombolysis might arguably the most biologically suggestive signal in the benefit the phenotype it sampled. Treatment guidelines trial. still withhold antiplatelets for 24 h after thrombolysis Assessment of safety is harder in TAPIS. Symptomatic and do not fully endorse tirofiban.6 TAPIS might not intracranial haemorrhage within 36 h occurred in six change that tomorrow, but it is a key piece of evidence versus five patients (risk ratio 1·20 [95% CI 0·37–3·93); about a specific stroke biology. More such pieces, from the low event rate might not allow a confident safety more regions, are what a mature, global, evidence base inference, especially when the 95% upper bound looks like: biology, not geography, determines where suggests a near four-times increase. Moreover, if benefit lies. the principal benefit of ticagrelor and aspirin were I declare no competing interests. prevention of re-occlusion, one might expect a lower Bijoy K Menon rate of recurrent ischaemic stroke in that group; this bkmmenon@ucalgary.ca was not the case. The rescue-therapy imbalance points Department of Clinical Neurosciences, Department of Radiology, Cumming indirectly towards prevention of early re-thrombosis, School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, but without serial vascular imaging, this remains Canada; Hotchkiss Brain Institute, Calgary, AB, Canada inference, not proof. 1 Wang A, Xia X, Tang Y, et al. Ticagrelor with aspirin dual antiplatelet therapy combined with intravenous thrombolysis in patients with ischaemic stroke There is a habit in stroke medicine of treating in China (TAPIS): a multicentre, double-blind, randomised controlled trial. a positive trial from one region as provisional, Lancet 2026; published online May 8. https://doi.org/10.1016/ S0140-6736(26)00757-9. awaiting confirmation in another. That habit is worth 2 Chen HS, Cui Y, Li XQ, et al. Early antiplatelet treatment for minor stroke questioning. TAPIS is not a provisional finding; it is following thrombolysis: the EAST trial. Eur Heart J 2026; 47: 746–56. 3 Zinkstok SM, Roos YB. Early administration of aspirin in patients treated evidence about a specific biology of stroke. As trials with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet 2012; 380: 731–37. accumulate from more regions, stroke medicine gains 4 Adeoye O, Broderick J, Derdeyn CP, et al. Adjunctive intravenous argatroban a richer map of where treatments work, in whom, and or eptifibatide for ischemic stroke. N Engl J Med 2024; 391: 810–20. why. The goal is not to reduce this heterogeneity to a 5 Tao C, Liu T, Cui T, et al. Early tirofiban infusion after intravenous thrombolysis for stroke. N Engl J Med 2025; 393: 1191–201. single global answer but to act on regional evidence in 6 Prabhakaran S, Gonzalez NR, Zachrison KS, et al., 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline patients who share the biology such trials sampled. From the American Heart Association/American Stroke Association. Stroke TAPIS should not be read as practice changing, nor as 2026; published online Jan 26. doi:10.1161/STR.0000000000000513. provisional evidence needing replication. It is a positive Emerging β-lactam and β-lactamase inhibitor strategies for complicated urinary tract infections Complicated urinary tract infections (cUTIs) and carbapenem-sparing strategies.³ The phase 3 Integral-1 acute pyelonephritis remain major causes of trial evaluating cefepime–nacubactam and aztreonam– hospitalisation worldwide and contribute substantially nacubactam compared with imipenem–cilastatin, to antibiotic consumption and health-care costs.¹ The presented by Satoshi Takahashi and colleagues in increasing prevalence of antibiotic resistance among The Lancet, represents an important step towards Gram-negative bacterial pathogens, particularly expanding the potential therapeutic arsenal against See Articles page 1929 extended-spectrum β-lactamase (ESBL)-producing non-carbapenem resistant Gram-negative infections.⁴ Enterobacterales and carbapenem-resistant bacteria has Nacubactam is a diazabicyclooctane β-lactamase made effective treatment increasingly challenging.² inhibitor with a distinctive dual mechanism of action. In this context, the development of novel β-lactam Beyond inhibiting several classes of serine β-lactamases and β-lactamase inhibitor combinations aids (class A, class C, and some class D enzymes), nacubactam preservation of treatment options and supports also directly targets penicillin-binding protein 2 in segamI ytteG aiv 16dnetseW --- [PDF原文](https://sci-net.xyz/storage/7932541/fc38ff56fc06e6680b98ee4f526ca40f7f19a0aa1eae4fa58a6705be0955e967/TAPIS-a-positive-trial-in-a-defined-phenotype.pdf) DOI: 10.1016/S0140-6736(26)00820-2