Dataset Information

Renal safety evaluation of aspirin plus edaravone in patients with ischaemic stroke: a retrospective cohort study.

ABSTRACT:

Background and objective

Aspirin combined with edaravone is more effective than aspirin or edaravone alone in the treatment of ischaemic stroke. Aspirin is defined as a nephrotoxic drug while the renal safety of edaravone is controversial. We aimed to evaluate whether edaravone will increase the nephrotoxicity of aspirin in patients with ischaemic stroke.

Design

A propensity score-matched retrospective cohort study.

Setting

A tertiary hospital in China.

Participants

Patients with ischaemic stroke were treated with aspirin from February 2007 to May 2018.

Primary and secondary outcome measures

Acute kidney injury (AKI, diagnosed by the Acute Kidney Injury Network), decreased estimated glomerular filtration rate (eGFR,>10%), gastrointestinal bleeding and in-hospital adverse outcomes (defined as dying or giving up treatment in our hospital).

Results

We included 3061 patients, and 986 pairs were successfully matched. Of the 986 pairs of patients included, the incidence of AKI between the aspirin group and the combination group showed no significant difference (7.71% vs 6.29%, p=0.217). While the incidence of eGFR decline (24.75% vs 16.94%, p<0.001) was significantly lower in the combination group. The protective effect was significant in patients with baseline eGFR >30 mL/min/1.73 m², especially in eGFR 60-90 mL/min/1.73 m². In patients with different complications, the incidence of AKI showed no significant differences in patients with chronic kidney injury, hypertension, anaemia, age above 75 years, except in patients with cardiovascular disease (OR, 2.82; 95% CI 1.50 to 5.29; p<0.001). However, the incidence of gastrointestinal bleeding (1.22% vs 2.84%, p=0.011) and in-hospital adverse outcomes (3.25% vs 7.00%, p<0.001) were significantly higher in the combination group.

Conclusions

Our study indicated that edaravone in patients with ischaemic stroke didn't increase the nephrotoxicity of aspirin, and even had a protective effect on mild renal deterioration. Nevertheless, there is a need to be cautious when patients are in bad pathophysiological conditions and at high risk of bleeding.

SUBMITTER: Yang HQ

PROVIDER: S-EPMC9020313 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Renal safety evaluation of aspirin plus edaravone in patients with ischaemic stroke: a retrospective cohort study.

Yang Hui-Qin HQ Yin Wen-Jun WJ Liu Kun K Liu Man-Cang MC Zuo Xiao-Cong XC

BMJ open 20220419 4

<h4>Background and objective</h4>Aspirin combined with edaravone is more effective than aspirin or edaravone alone in the treatment of ischaemic stroke. Aspirin is defined as a nephrotoxic drug while the renal safety of edaravone is controversial. We aimed to evaluate whether edaravone will increase the nephrotoxicity of aspirin in patients with ischaemic stroke.<h4>Design</h4>A propensity score-matched retrospective cohort study.<h4>Setting</h4>A tertiary hospital in China.<h4>Participants</h4> ...[more]

PMID: 35440453

Similar Datasets

Project description:ObjectiveTo assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA).DesignSystematic review and meta-analysis of randomised, placebo controlled trials.Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018.Eligibility criteria for selecting studies and methodsTwo reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology.ResultsThree eligible trials involving 10 447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely.ConclusionsDual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.

Project description:What is known and objectiveEdaravone is a new antioxidant and hydroxyl radical scavenger. Although there is evidence that it improves clinical outcomes of patients with acute ischaemic stroke (AIS), it is not yet widely accepted for treatment of AIS in Western countries. We further investigated the efficacy and safety of edaravone through this meta-analysis of randomized controlled clinical trials (RCTs).MethodPubmed, Embase, Web of Science and Cochrane Library were screened up to December 2020 for original articles from SCI journals that published in English. RCTs that compared edaravone versus placebo or no intervention in adult patients and reported the efficacy or safety of edaravone were regarded as eligible. Mortality was regarded as the primary outcome and the improvement of neurological impairment was regarded as the secondary outcome. Safety evaluation was conducted according to the incidence of adverse events. Review Manager 5.3 was employed to perform the assessment of the risk of bias and data synthesis. The Cochrane risk of bias tool for randomized controlled trials was employed to assess the risk of bias.Results and discussionSeven randomized controlled trials with 2069 patients were included. For the incidence of mortality, the pooled RR for studies that evaluated edaravone after three-month follow-up was 0.55 (95% Cl, 0.43-0.7, I2 = 0, P < 0.01). The pooled RR for improvement of neurological impairment at the three months follow-up was 1.54 (95% CI, 1.27-1.87, I2 = 0, P < 0.01) in four RCTs. On subgroup analysis of studies that were conducted in Asia, the RR was 1.56 (95% CI, 1.27-1.90, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in Europe was 1.32 (95% CI, 0.64-2.72; P = 0.45); the pooled RR for studies that used edaravone for two weeks was 1.42 (95% CI, 1.10 to 1.83, I2 = 0%; P < 0.01); the pooled RR for studies that used edaravone for one week was 1.64 (95% CI, 1.24-2.16, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in patients with mean age equal to or over 60 years was 1.52 (95% CI, 1.24-1.87, I2 = 0%; P < 0.01); and the pooled RR for studies that conducted in patients with mean age less than 60 was 1.80 (95% CI, 1.05-3.08, I2 = 0%; P = 0.03). For the incidence of any treatment-related adverse events, the pooled RR for studies that evaluated edaravone during treatment was 0.83 (95% CI, 0.51-1.34, I2 = 0, P = 0.43). The difference of the incidence of any treatment-related adverse events between two groups was not statistically significant.What is new and conclusionThe limited studies indicate that edaravone can improve neurological impairment with a survival benefit at three-month follow-up, regardless of the mean age and course of treatment. It is worthy of promotion in the clinical treatment of AIS in Asian countries. More well-designed RCTs with larger sample sizes are needed to determine the benefits of edaravone in patients from Western countries.

Project description:ObjectiveTo test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis.DesignOpen label, blinded endpoint, randomised controlled phase II trial.SettingProspective studies conducted at 26 centres in China, August 2015 to March 2017.Participants675 patients with acute minor stroke or transient ischaemic attack.InterventionTicagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset.Main outcome measuresPrimary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year.ResultsAt 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42).ConclusionPatients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations.Trial registrationClinicaltrials.gov NCT02506140.

Project description:ObjectiveThe Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA).DesignEligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0-2 at day 90.ResultsTen UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13-21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0-1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0-2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021).ConclusionsThe trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival.Trial registration numberNCT01745692; Results.

Dataset Information

Renal safety evaluation of aspirin plus edaravone in patients with ischaemic stroke: a retrospective cohort study.

Background and objective

Design

Setting

Participants

Primary and secondary outcome measures

Results

Conclusions

Publications

Renal safety evaluation of aspirin plus edaravone in patients with ischaemic stroke: a retrospective cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets