Abstract
We have something to celebrate this month with the adoption of the first-ever World Health Organisation (WHO) resolution on stroke, proposed by Chile, Egypt, Georgia, Palestine, Paraguay, and Tunisia at the 158th session of the WHO Executive Board in February 2026, which was later adopted at the 79th World Health Assembly in May 2026 in Geneva. The resolution establishes the first, legally endorsed global framework for comprehensive stroke action across the full continuum of care. It calls for integrating stroke into national cardiovascular and neurological strategies, designating tiered stroke-ready facilities, establishing national stroke registries, and ensuring financial protection. The WHO Director-General is tasked with producing normative guidance, supporting low- and middle-income countries in developing context-appropriate stroke systems, and reporting progress to the Health Assembly. The contents of this resolution, and its important implications, are summarized in an article in this issue of the International Journal of Stroke (IJS) by Agboyibor et al. 1 Let’s hope this results in a step change in recognition of the importance of both stroke prevention and stroke care worldwide. A resolution such as this could only be achieved with input from many organizations including the WHO, the World Stroke Organisation (WSO), and the Global Stroke Action Coalition and emphasizes the importance of advocacy in stroke care. 2
Continuing on the theme of major stroke challenges that require concerted global action to address them, this month, we also publish the WSO scientific statement on stroke and climate change. 3 This is a comprehensive review of an increasing volume of literature on the topic. It concludes that cold exposure, temperature variability, and extreme thermal events are most consistently associated with increased stroke risk. Although cold effects are generally stronger than heat effects, heat effects have been increasing over time. The statement reviews potential biological mechanisms mediating these effects and advocates strategies that may be used to mitigate their effects, both in design and delivery of local stroke services, and also globally.
History of illicit drug use is something stroke clinicians often look for, particularly in patients with younger-onset stroke. However, the importance of substance abuse, and particularly of more widely utilized drugs such as cannabis, is less clear. It has also been questioned as to whether relationships may be causal, or could be due to confounding with sharing of other risk factors such as smoking. An article by Ritson et al., 4 also in this month’s issue of IJS, goes some way to answering these questions. They performed a systematic review and meta-analysis of studies reporting associations between illicit drug use and stroke and included 32 studies comprising more than 100 million total participants. The meta-analysis demonstrated significant associations of cannabis (odds ratio (OR) = 1.37, 95% confidence interval (95% CI) = 1.14–1.65), cocaine (OR = 1.96; 95% CI = 1.27–3.01), and amphetamines (OR = 2.22, 95% CI = 1.40–3.53) with increased stroke risk, while no significant association was observed for opioids. To explore whether relationships were causal, they then used Mendelian randomization techniques. They found that cannabis use disorder was associated with any stroke and large artery stroke, and cocaine dependence was associated with cardioembolic stroke and intracerebral hemorrhage (ICH).
Another paper by Brown et al., 5 also in this issue, provides further evidence that cannabis use is associated with stroke risk. They conducted a cross-sectional analysis of 122,767 adults from the National Institutes of Health All of Us Research Program who completed lifestyle surveys between 2017 and 2022, among which 2765 (2.3%) had a history of stroke. Overall, there was an increased odds of any stroke for weekly (OR = 1.39) and daily (OR = 1.44) users. However, different relationships were seen for ischemic stroke and ICH. Odds of ischemic stroke demonstrated a clear dose-response relationship concentrated among frequent (weekly or daily) users, while odds of haemorrhagic stroke were elevated across all frequencies of use.
Another major contribution to global stroke burden are socioeconomic inequalities. However, how these inequalities increase stroke risk is uncertain. Also in this issue of IJS, Pantoja-Ruiz et al. 6 performed a systematic review including observational studies, which had applied a causal mediation analysis between socioeconomic status and stroke risk, disability, or mortality. They conclude hypertension, smoking, and differential stroke severity at presentation are the main pathways through which low socioeconomic status increases stroke risk and causes worse outcomes. Taken together, these different papers mentioned earlier highlight the importance of education, and global initiatives improving stroke prevention, if we are to tackle the increasing burden of stroke, particularly in low- and middle-income countries. 7
One area of cardiovascular medicine which has been transformed recently is the management of elevated lipids. Dyslipidemia remains a major, modifiable determinant of global stroke burden, accounting for more than one-fifth of ischemic strokes worldwide. 8 In this issue of the IJS, Stefanou et al. 8 review this fast-moving area. They highlight how recent evidence has shifted emphasis from conventional lipid fractions to apolipoprotein B (ApoB)-containing lipoproteins, including lipoprotein(a) [Lp(a)], which more accurately reflect atherogenic particle burden than low-density lipoprotein cholesterol (LDL-C) alone and are increasingly used for stroke risk stratification. They cover the use of alternative agents beyond statins now available to control LDL-C, including ezetimibe and PCSK9 inhibitors. They highlight that Lp(a)-lowering agents are under active evaluation and may address residual cardiovascular risk. They propose a more individualized approach is needed for different patients. This review is a highly recommended reading for anyone who would like an update in this important area.
ICH remains a major burden and is associated with worse outcomes than other stroke subtypes. 9 A common question, when managing a patient with ICH, is whether antithrombotic medication should be continued if they have concurrent atherosclerosis or atrial fibrillation. To answer this, reliable data is required on the risk of recurrent ICH versus ischemic cardiovascular events, during follow-up after an initial ICH. An international collaborative systematic review and study-level meta-analysis, also published in this issue of IJS, provides important data in this area. 10 Putri et al. included 26 studies, involving 198,289 ICH survivors. Individual studies reported annual rate of major adverse cardiovascular and cerebrovascular events of between 4.2% and 14.6%. The pooled annual rate of recurrent ICH was 2.1% (95% CI = 1.7–2.6), and that of ischemic stroke was 2.0% (95% CI = 1.5–2.7). Meta-regression analyses identified one statistically significant association, between a higher prevalence of atrial fibrillation and an increased risk of ischemic stroke. This comprehensive analysis shows that the rates of recurrent ICH and ischemic stroke were comparable among ICH survivors, although the presence of atrial fibrillation does appear to be associated with an increased relative risk of ischemic stroke.
In last month’s issue of the IJS, a number of papers on hyperacute stroke were published, many of which involved fine-tuning the thrombolysis and thrombectomy processes to increase effectiveness. 11 Exciting approaches are now being evaluated to increase reperfusion. Early results from one such approach are published in this month’s issue. Human tissue kallikrein-1 (KLK1) is an endogenous serine protease primarily produced by the kidneys and is detectable in both blood and urine. KLK1 regulates vasodilation and blood flow by cleaving low-molecular-weight kininogen to release bradykinin. 12 Bradykinin binds to bradykinin 2 receptors which activate nitric oxide, prostacyclin, and endothelial-derived hyperpolarizing factor pathways. These mediators relax arterial smooth muscle cells, thereby dilating cerebral arteries and enhancing blood flow, particularly to ischemic tissues. 12 The ReMEDy1 trial tested the safety and tolerability of Rinvecalinase alfa (DM199), a recombinant form of human tissue KLK1 in patients with ischemic stroke with onset ⩽24 h and baseline National Institutes of Health Stroke Score (NIHSS) 6–25. Patients could receive thrombolysis, thrombectomy, or both, prior to enrolment if NIHSS was 6–25 more than 1 h after the completion of reperfusion therapy. Ninety-two patients were enrolled across 13 Australian sites. 12 Rinvecalinase alfa appeared to be safe and generally well-tolerated in ischemic stroke patients, with potential efficacy in reducing stroke progression. Stroke-in-evolution by day 90 occurred in 0 (0%) rinvecalinase alfa patients versus 6 (13.3%) placebo patients, although further studies are required to demonstrate efficacy.
Mobile stroke units, while costly, can provide faster thrombolysis therapy, particularly in remote areas. 13 One challenge can be the amount of time taken to reach the patient. A novel approach is to rendezvous with a local ambulance at a midway point. This was tested by Wu et al., 14 and results are published in this issue. In a non-randomized comparative study in Suzhou, China, 193 patients were transferred through rendezvous transport, and 114 patients were transferred through emergency medical services only. The median distance from onset location to hospital in the rendezvous transport group was 39 km. Compared with emergency medical services transfers, patients transferred through rendezvous transport had a nearly three-fold increase in thrombolysis rates (68.90% vs 17.50%, p < 0.001). In addition, in terms of clinical outcomes, patients in the rendezvous group had lower median 90-day modified Rankin Scale scores (2.0 (1.0–3.0) vs 3.0 (1.5–5.0), p < 0.001). These results are very promising, although it would be reassuring to have them confirmed in a randomized trial approach incorporating cost-effectiveness.
Finally, there is increasing interest in the modifying effect of frailty on stroke. As summarized in a recent WSO scientific statement, it has been associated with increased stroke risk and worse outcome after stroke. 15 An interesting article in this issue of IJS, by Wang et al., 16 suggests the relationship may be bidirectional. They analyzed longitudinal data from four prospective cohorts. Compared to stroke-free individuals, stroke survivors exhibited an observable increase in the frailty index prior to the stroke event, while a sharp increase in the frailty index occurred during the incident stroke event, followed by sustained post-stroke acceleration. They suggest that frailty accelerates significantly both before and after an incident stroke, suggesting a bidirectional relationship between stroke and frailty.