After an ischaemic stroke or transient ischaemic attack patients have a substantial lifelong risk of stroke recurrence, incident coronary events, and cardiovascular mortality.1,2 This risk remains ...high despite guideline-recommended treatments, such as lipid lowering agents, blood pressure control, and antithrombotics.3,4 Therefore, novel adjunctive preventive treatments are an important unmet need in this population.5 Inflammation has been associated with an increased risk of major adverse cardiovascular events, and in particular the risk of stroke recurrence in patients with large artery atherosclerosis or small vessel disease.6 Colchicine exhibits multiple anti-inflammatory effects and has been reported to downregulate the NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway involved in the pathogenesis of atherosclerosis and cerebral small vessel disease.7 Randomised controlled trials (RCTs) have established that colchicine reduces the risk of major adverse cardiovascular events (risk ratio RR 0·75, 95% CI 0·61–0·92) in patients with a history of coronary artery disease, with the most pronounced effect seen on incident stroke (0·54, 0·34–0·86), generating increasing interest in testing its effects for secondary stroke prevention.8 Peter Kelly and colleagues now report the results of colchicine for the prevention of vascular inflammation in non-cardioembolic stroke (CONVINCE).9 CONVINCE was a randomised, parallel-group, open-label, blinded endpoint trial comparing low-dose colchicine (0·5 mg orally per day) in addition to guideline-based usual care with usual care alone after non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack.9 The investigators recruited 3154 patients from 144 hospitals in 13 European countries and Canada. Patients were eligible if they had an ischaemic stroke attributed to large artery atherosclerosis, small vessel disease, or cryptogenic embolism.9 Patients after a transient ischaemic attack were also eligible if they had an ABCD2 score of 4 or more, large artery stenosis of at least 50%, or a hyperintense lesion on diffusion weighted imaging that corresponded to the clinical presentation.9 Patients were excluded in the presence of substantial disability (modified Rankin score of 4 or 5), contraindications to colchicine treatment, cardioembolic sources or other defined stroke mechanisms.9 Consenting participants were randomly assigned between 72 h and 28 days from the qualifying event to either a daily dose of 0·5 mg open-label colchicine or no colchicine. In the intention-to-treat analysis, the incidence of the primary efficacy outcome was similar between participants allocated to colchicine or no colchicine treatment over a median follow-up duration of 33·6 months (153 9·8% of 1569 patients allocated to colchicine and usual care and 185 11·7% of 1575 patients allocated to usual care alone incidence rates 3·33 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68–1·05, p=0·12).9 One of five participants (21%) allocated to receive colchicine permanently discontinued the trial medication during follow-up, while ten (0·6%) did not receive a single dose of colchicine following randomisation.9 In the prespecified on-treatment analysis, excluding participants who did not begin colchicine treatment and censoring for the timing of non-cardiovascular death, loss-to-follow-up, or permanent colchicine discontinuation, participants treated with colchicine had a substantially lower risk for the primary efficacy outcome compared with those not receiving colchicine (3·2 vs 3·92 per 100 person-years, HR 0·796 95% CI 0·63–0·9992).9 The systemic anti-inflammatory effects of colchicine treatment were evident with a 15% relative reduction in C-reactive protein values at 28 days followed by a roughly 20% reduction in C-reactive protein up to 3 years compared with no colchicine treatment.9 Consistent with findings from previous RCTs, diarrhoea, loose stools, and nausea were more frequent in patients treated with colchicine than in those treated with placebo.9 Serious adverse events were similar between the two groups, including the rates of extracranial bleeding and intracranial haemorrhage not lending support to the postulated pleiotropic antiplatelet effects of colchicine.10 CONVINCE provides landmark evidence on the safety and tolerability of long-term colchicine treatment for patients with an acute ischaemic stroke or transient ischaemic attack, but has fallen short of establishing an added benefit from low-dose colchicine in reducing the risk of major adverse cardiovascular events after a non-cardioembolic stroke or transient ischaemic attack.
Randomized controlled trials (RCTs) have recently established the benefit of endovascular thrombectomy (EVT) in patients with large infarct core on baseline neuroimaging. We evaluated the utility of ...EVT in patients with very large infarct core, defined as Alberta Stroke Program Early CT scores (ASPECTS) of less than 3.
We performed a systematic review and meta-analysis of the subgroups of patients with baseline ASPECTS scores 0-2 included in RCTs evaluating the utility of EVT in the setting of a large infarct core. The outcome of interest was the probability of three-month functional improvement assessed with the generalized odds ratios (ORs) of the modified Rankin Scale (mRS) scores between patients receiving EVT and medical management.
In the pooled analyses of 82 participants of the total 808 (10%) enrolled in 2 individual trials, we found a statistically significant shift in the distribution of mRS scores toward better outcomes in favor of EVT (generalized OR 1.46, 95% CI 1.03-2.07). No evidence of heterogeneity was detected (
= 0%;
for Cochran
= 0.73).
The results from our pooled analysis challenge the exclusion of patients presenting with ASPECTS scores less than 3 from receiving EVT if they are otherwise eligible.
This scientific commentary refers to ‘Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk’ by Mayerhofer et al. ...(https://doi.org/10.1093/brain/awac186).
Alteplase is currently the only approved thrombolytic agent for treatment of acute ischaemic stroke, but interest is burgeoning in the development of new thrombolytic agents for systemic reperfusion ...with an improved safety profile, increased efficacy, and convenient delivery. Tenecteplase has emerged as a potential alternative thrombolytic agent that might be preferred over alteplase because of its ease of administration and reported efficacy in patients with large vessel occlusion. Ongoing research efforts are also looking at potential improvements in recanalisation with the use of adjunct therapies to intravenous thrombolysis. New treatment strategies are also emerging that aim to reduce the risk of vessel reocclusion after intravenous thrombolysis administration. Other research endeavors are looking at the use of intra-arterial thrombolysis after mechanical thrombectomy to induce tissue reperfusion. The growing implementation of mobile stroke units and advanced neuroimaging could boost the number of patients who can receive intravenous thrombolysis by shortening onset-to-treatment times and identifying patients with salvageable penumbra. Continued improvements in this area will be essential to facilitate the ongoing research endeavors and to improve delivery of new interventions.
To summarize available evidence on the potential utility of pretreatment with intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) ...patients with large vessel occlusions (LVO) who are treated with mechanical thrombectomy.
Despite theoretical concerns of a higher bleeding risk with IVT pretreatment, there are no data showing increased risk of symptomatic intracerebral hemorrhage (sICH) in patients with LVO receiving bridging therapy (IVT and mechanical thrombectomy) compared with direct mechanical thrombectomy (dMT). Additionally, evidence from observational studies suggest lower rates of infarctions in previously unaffected territories and higher rates of successful reperfusion, with lower number of device passes, in patients receiving bridging therapy. There are substantial discrepancies in studies comparing clinical outcomes between dMT and bridging therapy that are directly related to the inclusion of patients with contraindications to IVT in the dMT group. Ongoing clinical trials will provide definitive answers on the potential additional benefit of IVT in LVO patients receiving mechanical thrombectomy.
IVT and mechanical thrombectomy are two effective reperfusion therapies that should be used in a swift and noncompeting fashion in AIS patients. AIS patients with LVO and no contraindications for IVT should receive promptly rt-PA bolus followed by immediate initiation of mechanical thrombectomy as indicated by current international recommendations, unless future randomized controlled trials provide evidence to proceed differently.
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