Noninfectious complications of acute stroke and their impact on hospital mortality in patients admitted to a stroke unit in Warsaw from 1995 to 2015

Background Medical complications often worsen the prognosis after stroke. Our aim was to investigate the association between particular noninfectious complications and hospital mortality of acute stroke patients admitted to an urban Polish stroke center, and changes in their occurrence from 1995 to 2015. Methods This is a retrospective analysis of 5174 consecutive patients admitted for acute ischemic stroke or cerebral hemorrhage to a Polish urban stroke center between 1995 and 2015. The occurrence of complications was reported for years 1995–2000 (n=883), 2001–2006 (n=1567), 2006–2010 (n=1539) and 2011–2015 (n=1183). Odds ratios (OR) with 95% confidence interval (95% CI) for stroke unit death were calculated after adjustment for age, congestive heart failure (CHF), pre-existing disability, stroke type and baseline neurological deficit in three different time periods. Results Over time there was a significant decrease in the occurrence of myocardial infarction (MI) (2.2%, 1.4%, 1.0% and 0.3%, respectively), exacerbated CHF (4.6%, 5.1%, 2.6% and 2.0%) and deep vein thrombosis (DVT) (4.6%, 2.7%, 1.2% and 1.1%). Adjusted odds for stroke unit death were increased by myocardial infarction (MI) (OR 17.5, 95% CI: 8.5–35.7), exacerbated CHF (OR 15.0, 95% CI: 9.8–23.0), pulmonary embolism (PE) (OR 11.5, 95% CI: 6.1–21.6), gastrointestinal bleeding (OR 9.2, 95% CI: 4.4–18.9) and recurrent stroke (OR 5.4, 95% CI: 3.1–9.3). Conclusions Over the last two decades Polish urban stroke units may have achieved a significant reduction of the occurrence of some noninfectious complications (i.e. MI, exacerbated CHF and DVT). However, the list of conditions associated with stroke unit mortality includes not only MI and exacerbated CHF but also PE, gastrointestinal bleeding and recurrent stroke

Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: a secondary analysis of a large randomised controlled trial

BACKGROUND: Tranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there was a statistically significant interaction between prerandomisation baseline systolic blood pressure (SBP) and the effect of tranexamic acid on functional outcome (p=0.019). METHODS: TICH-2 was an international prospective double-blind placebo-controlled randomised trial evaluating intravenous tranexamic acid in patients with acute spontaneous intracerebral haemorrhage (ICH). Prerandomisation baseline SBP was split into predefined ≤170 and >170 mm Hg groups. The primary outcome at day 90 was the modified Rankin Scale (mRS), a measure of dependency, analysed using ordinal logistic regression. Haematoma expansion was defined as an increase in haematoma volume of >33% or >6 mL from baseline to 24 hours. Data are OR or common OR (cOR) with 95% CIs, with significance at p170 mm Hg. Tranexamic acid was associated with a favourable shift in mRS at day 90 in those with baseline SBP≤170 mm Hg (cOR 0.73, 95% CI 0.59 to 0.91, p=0.005), but not in those with baseline SBP>170 mm Hg (cOR 1.05, 95% CI 0.85 to 1.30, p=0.63). In those with baseline SBP≤170 mm Hg, tranexamic acid reduced haematoma expansion (OR 0.62, 95% CI 0.47 to 0.82, p=0.001), but not in those with baseline SBP>170 mm Hg (OR 1.02, 95% CI 0.77 to 1.35, p=0.90). CONCLUSIONS: Tranexamic acid was associated with improved clinical and radiological outcomes in ICH patients with baseline SBP≤170 mm Hg. Further research is needed to establish whether certain subgroups may benefit from tranexamic acid in acute ICH. TRIAL REGISTRATION NUMBER: ISRCTN93732214

Early stroke-related deep venous thrombosis: risk factors and influence on outcome

Deep venous thrombosis (DVT) is a serious complication of various medical conditions including acute stroke. Our aim was to identify the occurrence of early stroke-related DVT, risk factors for its development and the influence on outcome. The study involved consecutive patients admitted to our center due to acute ischaemic (n = 278) or haemorrhagic (n = 12) stroke during a 16-month period. We collected data on their pre-stroke health status, neurological deficit on admission and baseline serum CRP and fibrinogen level. Ultrasonographic imaging was performed at the 3rd (IQR: 2–4) and 9th (IQR: 8–9) day after stroke. Patients thrombosis occurring between the first and second examination comprised the newly developed early stroke-related DVT group. We found DVT in 8.0% (24/299) of patients at initial evaluation. Newly developed DVT was present in 3.0% (9/299) of patients, and was predominantly distal (7 of 9 cases). It was associated with elevated serum CRP level (OR 8.75; 95%CI: 1.61–47.6), which was verified in a model adjusted for stroke severity and pre-stroke dependency (3–5 pts. in mRS). In a multivariate model, newly developed DVT significantly increased the risk of 3-month mortality (OR 12.4; 95%CI: 1.72–89.4), without affecting the combined risk of dependency and death (OR 2.57; 95%CI: 0.39–17.0). Early stroke-related DVT is an infrequent complication. However, it may be an independent risk factor for 3-month mortality. Increased serum CRP level combined with normal fibrinogen level seems predictive for development of DVT. It may be reasonable to provide those patients with additional DVT prophylaxis

Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT

BACKGROUND: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH). DESIGN: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial. SETTING: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK). PARTICIPANTS: Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset. EXCLUSION CRITERIA: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy  4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK. CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events. FUTURE WORK: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93732214. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland

Effectiveness and safety of a single freeze strategy of cryoballoon ablation of atrial fibrillation: an EHRA systematic review and meta-analysis.

To conduct a systematic review and meta-analysis to compare the effectiveness and safety of cryoballoon ablation of atrial fibrillation (AF) performed using a single freeze strategy in comparison to an empiric double ('bonus') freeze strategy. We systematically searched MEDLINE, EMBASE, and CENTRAL databases from inception to 12 July 2020, for prospective and retrospective studies of patients undergoing cryoballoon for paroxysmal or persistent AF comparing a single vs. bonus freeze strategy. The main outcome was atrial arrhythmia-free survival and eligible studies required at least 12 months of follow-up; the primary safety outcome was a composite of all complications. Study quality was assessed using the Cochrane risk of bias tool and the Newcastle-Ottawa Scale. Thirteen studies (3 randomized controlled trials and 10 observational studies) comprising 3163 patients were eligible for inclusion (64% males, 71.5% paroxysmal AF, mean CHA2DS2-VASc score 1.3 ± 0.9). There was no significant difference in pooled effectiveness between single freeze strategy compared to double freeze strategy [relative risk (RR) 1.03; 95% confidence interval (CI): 0.98-1.07; I2 = 0%]. Single freeze procedures were associated with a significantly lower adverse event rate (RR 0.72; 95% CI: 0.53-0.98; I2 = 0%) and shorter average procedure time (90 ± 27 min vs. 121 ± 36 min, P < 0.001). A trend for lower risk of persistent phrenic nerve palsy was observed (RR 0.61; 95% CI: 0.37-1.01; I2 = 0%). The quality of included studies was moderate/good, with no evidence of significant publication bias. Single freeze strategy for cryoballoon of AF is as effective as an empiric double ('bonus') freeze strategy while appearing safer and probably quicker (PROSPERO registration number CRD42020158696)

Dabigatran initiation in patients with non-valvular AF and first acute ischaemic stroke: a retrospective observational study from the SITS registry

BACKGROUND AND OBJECTIVE: The optimal timing for initiation of dabigatran after acute ischaemic stroke (AIS) is not established. We aimed to evaluate initiation timing and clinical outcomes of dabigatran in AIS patients with non-valvular atrial fibrillation (NVAF). DESIGN: Retrospective study based on prospectively collected data in SITS (Safe Implementation of Treatment in Stroke) Thrombolysis and Thrombectomy Registry from July 2014 to July 2018. PARTICIPANTS: European NVAF patients (&ge;18 years) hospitalised after first-ever ischaemic stroke. SETTING: A multinational, observational monitoring register. INTERVENTION: Dabigatran initiation within 3 months after the ischaemic stroke. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was time from first-ever ischaemic stroke (index event) to dabigatran initiation. Additional outcomes included physicians\u27 reasons for delaying dabigatran initiation beyond acute hospital discharge and outcomes within 3 months of index event. METHODS: We identified patients with NVAF who received dabigatran within 3 months of the index event. We performed descriptive statistics for baseline and demographic data and clinical outcomes after dabigatran initiation. RESULTS: In total, 1489 patients with NVAF received dabigatran after AIS treated with thrombolysis and/or thrombectomy. Of these, 1240 had available initiation time. At baseline, median age was 75 years; 53% of patients were women, 15% were receiving an oral anticoagulant, 29% acetylsalicylic acid and 4% clopidogrel. Most patients (82%) initiated dabigatran within 14 days after the index event. Patients initiating earlier had lower stroke severity from median NIHSS 8 (IQR 6-13) if initiated within 7 days to NIHSS 15 (9-19) if initiated between 28 days and 3 months. Most common reasons for delaying initiation were haemorrhagic transformation or intracranial haemorrhage, stroke severity and infarct size. Few thrombotic/haemorrhagic events occurred within 3 months after the index event (20 of 926 patients, 2.2% with the available data). CONCLUSIONS: Our findings, together with previous observational studies, indicate that dabigatran initiated within the first days after an AIS is safe in patients treated with intravenous thrombolysis, endovascular thrombectomy or both

Outcomes in Antiplatelet‐Associated Intracerebral Hemorrhage in the TICH‐2 Randomized Controlled Trial

BackgroundAntiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain.Methods and ResultsThis is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248).ConclusionsAntiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use

The effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: a secondary analysis of a large randomised controlled trial

BackgroundTranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there was a statistically significant interaction between prerandomisation baseline systolic blood pressure (SBP) and the effect of tranexamic acid on functional outcome (p=0.019).MethodsTICH-2 was an international prospective double-blind placebo-controlled randomised trial evaluating intravenous tranexamic acid in patients with acute spontaneous intracerebral haemorrhage (ICH). Prerandomisation baseline SBP was split into predefined ≤170 and >170 mm Hg groups. The primary outcome at day 90 was the modified Rankin Scale (mRS), a measure of dependency, analysed using ordinal logistic regression. Haematoma expansion was defined as an increase in haematoma volume of >33% or >6 mL from baseline to 24 hours. Data are OR or common OR (cOR) with 95% CIs, with significance at pResultsOf 2325 participants in TICH-2, 1152 had baseline SBP≤170 mm Hg and were older, had larger lobar haematomas and were randomised later than 1173 with baseline SBP>170 mm Hg. Tranexamic acid was associated with a favourable shift in mRS at day 90 in those with baseline SBP≤170 mm Hg (cOR 0.73, 95% CI 0.59 to 0.91, p=0.005), but not in those with baseline SBP>170 mm Hg (cOR 1.05, 95% CI 0.85 to 1.30, p=0.63). In those with baseline SBP≤170 mm Hg, tranexamic acid reduced haematoma expansion (OR 0.62, 95% CI 0.47 to 0.82, p=0.001), but not in those with baseline SBP>170 mm Hg (OR 1.02, 95% CI 0.77 to 1.35, p=0.90).ConclusionsTranexamic acid was associated with improved clinical and radiological outcomes in ICH patients with baseline SBP≤170 mm Hg. Further research is needed to establish whether certain subgroups may benefit from tranexamic acid in acute ICH.Trial registration numberISRCTN93732214