ABSTRACT
Background and aims: Atrial fibrillation (AF) causes at least one-fifth of ischaemic strokes, with a high risk of early recurrence. Oral anticoagulation is highly effective for reducing the long-term risk of recurrent ischaemic stroke in patients with AF. However, its benefit in the acute phase is unclear. OPTIMAS is an RCT aiming to establish the safety and efficacy of early anticoagulation with a direct oral anticoagulant (DOAC). Methods: OPTIMAS will enrol 3,478 participants with ischaemic stroke and AF from 100+ stroke services in the UK. Participants are randomised 1:1 to early (within 4 days) or standard (day 7 to 14 after stroke) initiation of anticoagulation. Follow-up is at 90 days, blinded to treatment allocation. The primary outcome is the incidence of stroke of any cause, and systemic arterial embolism. Results: OPTIMAS opened in June 2019 and is recruiting from 87 sites. 1,714 participants have been randomised. Recruitment and site-set up were reduced during the COVID-19 pandemic, due to national lockdowns and hospital staff being reallocated to COVID-related trials. We rapidly developed a contingency plan to face these challenges, implementing strategies, such as collecting the 90-day follow-ups and obtaining consents over the phone, and encouraging sites to sign up to the NIHR Associate PI Scheme to help with trial-related activities. The trial has consistently been recruiting 80+ patients per month. Conclusions: OPTIMAS will determine the efficacy and safety of early anticoagulation in patients with ischaemic strokes and AF. The trial is recruiting successfully despite COVID-19.
ABSTRACT
BACKGROUND AND PURPOSE: There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19. METHODS: We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data. RESULTS: We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53-67) years and 64% (95% CI 54-73.7%) were male; 79% (95% CI 70.0-86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3-76.0%), and of multifocal ICH was 36% (95% CI 26.4-47.0%). 71% (95% CI 61.0-80.4%) of patients were treated with anticoagulation (58% (95% CI 48-67.8%) therapeutic). The median NIHSS was 28 (IQR 15-28); mortality was 54% (95% CI 43.7-64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22-0.58%). CONCLUSIONS: Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials.